FORMULATION
TECHNOLOGY PRACTICAL
MANUAL
RESHMA FATHIMA.K
ASSISTANT PROFESSOR
GRACE COLLEGE OF PHARMACY, PALAKKAD
1
EXP.NO: 1
DATE:
FORMULATION AND COMPARITIVE EVALUATION OF
MARKETED PARACETAMOL TABLETS
AIM
To formulate and evaluate the paracetamol tablets and compare it with the
uncoated (marketed tablets)
OBJECTIVE
To study the comparative quality evaluation of paracetamol tablet with
marketed paracetamol tablets to select the best formulation.
MATERIALS REQUIRED
APPARATUS: Mortar and pestle, beaker, sieve # 10, tablet punching machine,
hot air oven.
CHEMICALS: Paracetamol, lactose, dry starch, magnesium stearate, talc.
THEORY
Paracetamol has analgesic and antipyretic properties but it has no useful antiinflammatory
properties.
Paracetamol
is
readily
absorbed
from
the
gastrointestinal tract. Paracetamol is categorized under BCS classification II
Tablets are solid dosage forms containing one or more drugs with or
without excipients, prepared by compression. It provides greatest dose precision
and least content variability. Inert materials employed in addition to active
ingredients are collectively called tablet additives.
They include
2
1. DILUENTS: are fillers designed to make up the required weight of the tablet.
Eg: lactose, inorganic dicalcium salts microcrystalline cellulose etc.
2. BINDING AGENTS: are added in dry or in liquid form to obtain cohesive
mass for direct compression. Eg: Cellulose derivatives, gelatin solution, glucose
syrup, tragacanth mucilage etc.
3. DISINTEGRATING AGENTS: are added to facilitate breakup of the tablet
when in contact with gastrointestinal fluids. Eg: dry starch, starch derivatives,
clays, cellulose, cellulose derivatives, alginates
4. ADSORBENTS: included when formulation contains liquids, volatile oils etc.
5. ANTIFRICTIONAL AGENTS: enhance flow properties. Eg : talc, corn starch,
silica derivatives etc.
The usual methods of formulation include wet granulation, dry granulation
and direct compression. The most widely used and most general method of tablet
preparation is the wet granulation method. The active ingredient, diluent and
disintegrents are mixed or blended well. Solutions of the binding agent are added
to the mixed powder with stirring. The powder mass is wetted with the binding
solution until the mass has the consistency of damp snow. If the granulation is
over wetted the granules will be hard, if not wetted sufficiently, the resulting
granules will be too soft, breaking down during lubrication. The wet mass is
forced through a 6 or 8 mesh (Mesh no. is the number of wires passing through
an inch) screen or several mills can be used .Moist materials from wet milling
steps is placed on large trays and placed in drying chambers with a circulating air
current and thermostable heat controller. Commonly used dryers are tray dryer,
fluidized bed dryer. After drying, the granulation is reduced in particle size by
passing smaller mesh screen.
After drying granulation, the lubricant or glidants is added as fine powder to
promote flow of granules. These granules then compressed to get tablet
3
Tablets are evaluated for their general appearance, hardness, friability,
drug content, release, weight variation, dissolution and disintegration properties.
PROCEDURE
FORMULA FOR DESIGN OF PARACETAMOL TABLETS:
INGREDIENTS
FOR
FOR
1 TABLET(mg)
40 TABLETS(g)
Paracetamol (drug)
125
5g
Lactose (diluent)
375
15g
Drystarch(binder
48
1.92g
Talc (glidant)
40
1.6g
Magnesium
12
0.48g
&disintegrant)
stearate(lubricant)
5%starch was used as the binding agent.
The tablets was granulated using wet granulation method as follows.
Paracetamol, lactose and half the quantity of starch were weighed and mixed
thoroughly. It was granulated using 5% starch mucilage as binding agent and
passed through no.10 mesh screen. The obtained the granules were dried at 55ᵒC
for 1 hr. After drying, dry screening was done using no.22 mesh screen. The rest
of the starch powder along with talc and magnesium stearate were added and
mixed. These granules were compressed into tablets on a 16 station CADMACH
rotary tablet machine (12mm).
4
EVALUATION OF TABLETS
1. Hardness Test: Tablet hardness was measured using Monsanto hardness test
apparatus.
2. Weight Variation Test: 20 tablets are weighed individually. Calculated the
average weight and individual weight are compared with the average weight.
3. Friability Test: Friability is a measure of mechanical strength of the tablet. If
a tablet has more friability it may not remain intact during packaging, transport
or handling. Roche friabilator is used to determine the friability by following
procedure. Pre weighed tablets are placed in the friabilator. Friabilator consist of
a plastic chamber that revolves at 25 rpm, dropping those tablets at a distance of
6 inches with each revolution. The tablets are rotated in the friabilator for at least
4 minutes. At the end of test tablets are dusted and reweighed; the loss in the
weight of tablet is the measure of friability and is expressed in percentage as:
% Friability = 1‐ (loss in weight / Initial weight) X 100
4. Assay: 20 tablets are powdered and weighed. A quantity of powder equivalent
to about 0.15g of paracetamol are accurately weighed and added 50ml of 0.1M
sodium hydroxide, diluted with 100ml of water, and shaked for 15 mins and
added sufficient water to produce 250ml. They are mixed filtered and diluted
10ml of the filtrate to 100ml with water. To 10ml of resulting solution 10ml of
0.1M sodium hydroxide are added and diluted to 100ml with water and mixed.
The absorbance of the resulting solution at the maximum at about 257nm were
measured by using UV-Visible spectroscopy.
5. Disintegration Study
Experimental conditions were:
Medium: water
Speed: 30cycles/minute
5
Temperature: 37±0.5ᵒC
One tablet was added into each of the 6 tubes of the apparatus and the assembly
was suspended in a beaker containing water and time required to disintegrate each
tablet was noted. From this average disintegration time was determined.
6. Dissolution Study: The study was carried out using Type-2 Paddle type USP
apparatus. The set condition was 900ml of 6.8pH phosphate buffer, at 50 rpm,
37ᵒC for 45 minutes, 5ml of samples were withdrawn at time intervals of 5, 15,
30, 45 minutes, which was replaced by fresh equal volume of dissolution medium,
the sample was diluted suitably, assayed at 249nm by using UV-Visible
spectroscopy. The calibration curve was used to determine the drug concentration
per ml. The amount of drug release was calculated using calibration curve
method.
Amount of drug release =
Percentage drug release =
𝑐𝑜𝑛𝑐.×𝑣𝑜𝑙.𝑜𝑓.𝑑𝑖𝑠𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝑚𝑒𝑑𝑖𝑢𝑚×𝑑𝑖𝑙 𝑓𝑎𝑐𝑡𝑜𝑟
1000
𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑟𝑒𝑙𝑒𝑎𝑠𝑒
𝑠𝑡𝑟𝑒𝑛𝑔𝑡ℎ
x 100
REPORT
The formulation and comparative evaluation of marketed paracetamol tablets was
performed.
The results of study indicate F2 formulation (vamol) showed better quality than
that of other formulations.
REFERENCE
1. Lachman L Lieberman H.A, Kanig J.L, The Theory and Practice of Industrial
Pharmacy, 3rd edition
2. Michael E.Aulton. Pharmaceutics, The science of Dosage form design.
3. Indian pharmacopoeia, 1996
6
EXP.NO: 2
DATE:
FORMULATION AND EVALUATION OF CALCIUM ALGINATE
BEADS LOADED WITH DICLOFENAC SODIUM
AIM
To formulate and evaluate the calcium alginate beads of diclofenac
sodium.
OBJECTIVE
To develop the extended release dosage form of diclofenac sodium.
MATERIALS REQUIRED
APPARATUS: beaker, magnetic stirrer, standard flask, dissolution apparatus
CHEMICALS: 6.8 pH phosphate buffer, sodium alginate, diclofenac sodium, 2%
solution of calcium chloride, glutaraldehyde.
THEORY
Diclofenac sodium is one of the drugs of choice to treat arthritis because
of its potential anti- inflammatory and analgesic activity and this is the only
approved NSAID available for parenteral delivery. Because of shorter biological
half-life, diclofenac sodium should be given frequently to maintain its therapeutic
activity.
The United States Pharmacopoeia (USP) defines the modified-release
(MR) dosage form as “the one for which the drug release characteristics of time
course and/or location are chosen to accomplish therapeutic or convenience
objectives not offered by conventional dosage forms such as solutions, ointments,
or promptly dissolving dosage forms”. One class of MR dosage form is an
extended-release (ER) dosage form and is defined as the one that allows at least
7
a 2-fold reduction in dosing frequency or significant increase in patient
compliance or therapeutic performance when compared with that presented
As a conventional dosage form (a solution or a prompt drug-releasing dosage
form). The terms “controlled release (CR)”, “prolonged release”,“sustained or
slow release (SR)” and “long-acting (LA)” have been used synonymously with
“extended release”. Nearly all of the currently marketed monolithic oral ER
dosage forms fall into one of the following two technologies:
1. Hydrophilic, hydrophobic or inert matrix systems: These consist of a rate
controlling polymer matrix through which the drug is dissolved or dispersed.
2. Reservoir (coated) systems where drug containing core is enclosed within a
polymer coating. Depending on the polymer used, two types of reservoir systems
are considered.
(a) Simple diffusion/erosion systems where a drug-containing core is enclosed
within hydrophilic and/or water-insoluble polymer coatings. Drug release is
achieved by diffusion of the drug through the coating or after the erosion of the
polymer coating.
(b) Osmotic systems where the drug core is contained within a semi-permeable
polymer membrane with a mechanical/laser drilled hole for drug delivery. Drug
release is achieved by osmotic pressure generated within the tablet core.
CLINICAL ADVANTAGES:
 Reduction in frequency of drug administration
 Improved patient compliance
 Reduction in drug level fluctuation in blood
 Reduction in total drug usage when compared with conventional therapy
 Reduction in drug accumulation with chronic therapy
 Reduction in drug toxicity (local/systemic)
 Stabilization of medical condition (because of more uniform drug levels)
 Improvement in bioavailability of some drugs because of spatial control
8
 Economical to the health care provider and the patient
LIMITATIONS:
 Delay in onset of drug action
 Possibility of dose dumping in the case of a poor formulation strategy
 Increased potential for first pass metabolism
 Greater dependence on GI residence time of dosage form
 Possibility of less accurate dose adjustment in some cases
 Cost per unit dose is higher when compared with conventional doses
 Not all drugs are suitable for formulating into ER dosage form
Small beads are prepared from different polymers and other
pharmaceutical additives like microcrystalline cellulose and they are used carriers
for development oral sustained release capsules. These beads are filled into the
capsules and they are termed as spansules. The release rate of drugs from these
beads can be altered fast or slow release by coating with various amounts of
polymers. The time of release of drugs from the beads can be modified by
adjusting the thickness of polymer coat. Finally the beads coated with different
thickness and also mixed in different ratios can be put into capsules subsequently
used as modified release capsules.
PROCEDURE
Accurately weighed 500mg of sodium alginate and mixed. 25ml of
distilled water was added. This mixture was stirred by using a mechanical stirrer.
To this solution 500mg of diclofenac sodium was added and it is mixed well. By
using a syringe these solution was slowly introduced into a beaker containing 5%
solution of calcium chloride which is kept under slow continuous agitation using
a magnetic stirrer for 15 mins. The beads were filtered and dried at 40oC for 6hrs.
9
EVALUATION
Determination of drug content: 100 mg of beads was transferred into 100ml of
phosphate buffer 6.8 pH. The dispersion was stirred using a magnetic stirrer for
2 hrs. The solution was filtered and diluted with suitable solution. Then the
absorbance was measured at 275nm. The drug content of the prepared beads were
determined.
Percentage Drug Entrapment (%DE): Accurately weighed 100mg of
microsphere were dissolved in 100ml PBS pH 6.8. The solution was kept
overnight and was filtered through whatman filter 0.45µm. The drug
concentration was determined by UV spectrometer at maximum wavelength of
276nm. The following equation was used to calculate % drug entrapment:
% Drug Entrapment =
practical drug content
theoretical drug content
× 100
Determination of Swelling Index: 500mg of beads was taken in a China dish
and then 10 ml of distilled water was added and the mixture was shaken and
allowed to stand for 1hour. After 1 hour the remaining water in China dish was
discarded and the weight increase of the natural suspending agent was rated.
Swelling Index % (SI) = (W2 – W1/W2) x 100
W1=dry weight
W2= Wet weight
Dissolution Test: The study was carried out using Type-2 Paddle type USP
apparatus. The set condition was 900ml of 6.8pH phosphate buffer, at 50 rpm,
37ᵒC for 45 minutes, 5ml of samples were withdrawn at time intervals of 5, 15,
30, 45, 60minutes, 1hr and 2hr. which was replaced by fresh equal volume of
dissolution medium, the sample was diluted suitably, assayed at 275nm by using
UV-Visible spectroscopy. The calibration curve was used to determine the drug
10
concentration per ml. The amount of drug release was calculated using calibration
curve method.
Amount of drug release =
Percentage drug release =
𝑐𝑜𝑛𝑐.×𝑣𝑜𝑙.𝑜𝑓.𝑑𝑖𝑠𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝑚𝑒𝑑𝑖𝑢𝑚×𝑑𝑖𝑙 𝑓𝑎𝑐𝑡𝑜𝑟
1000
𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑟𝑒𝑙𝑒𝑎𝑠𝑒
𝑠𝑡𝑟𝑒𝑛𝑔𝑡ℎ
x 100
REPORT
The formulation and evaluation of calcium alginate beads of diclofenac sodium
was performed.
The percentage drug release of diclofenac sodium beads was found to be
REFERENCES
1. Leon Lachmann, Liebermann.H.A.Kaning JL, Theory and practice of
industrial pharmacy,3rd edition,420-428
2. S.P.Vyas, R.K.Khar, “Targeted and Controlled drug delivery”, novel
carrier system, CBS publishers and distributors, New Delhi, page no: 122
11
EXP.NO: 3
DATE:
DEVELOPMENT AND EVALUATION OF BOVINE SERUM ALBUMIN
MICROSPHERES LOADED WITH DICLOFENAC SODIUM
AIM
To formulate and evaluate microspheres of diclofenac sodium using bovine
serum albumin.
OBJECTIVE
To develop the modified release dosage form and to study their release
characteristics
MATERIALS REQUIRED
APPARATUS: beaker, magnetic stirrer, standard flask, dissolution apparatus
CHEMICALS: 6.8 pH phosphate buffer, bovine serum albumin, diclofenac
sodium, glutaraldehyde, liquid paraffin
THEORY
Diclofenac sodium is one of the drugs of choice to treat arthritis because
of its potential anti- inflammatory and analgesic activity and this is the only
approved NSAID available for parenteral delivery. Because of shorter biological
half-life, diclofenac sodium should be given frequently to maintain its therapeutic
activity.
It also has high percentage of protein binding and it undergoes presystemic
metabolism. To overcome these problems, many authors developed sustained
release formulations with an intention to maintain effective diclofenac
concentration for prolonged period. Microspheres are sometimes reffered to as
microparticles. Microspheres can be manufactured from various natural and
12
synthetic materials. Polymer used in this experiment is albumin. Albumin is a
natural polymers obtained from sources like proteins.
Methods
1. Single emulsion technique
2. Double emulsion technique
3. Polymerization
4. Phase separation/ Coacervation
5. Spray drying
6. Solvent extraction
7. Emulsion solvent evaporation
8. Wet emulsion technique
9. Hot melt microencapsulation
These are the methods used for the preparation for microspheres.
TYPES OF MICROSPHERES
Bioadhesive microspheres
Adhesion can be defined as sticking of drug to the membrane by using the
sticking property of the water soluble polymers. Adhesion of drug delivery
device to the mucosal membrane such as buccal, ocular, rectal, nasal etc can be
termed as bio adhesion. These kinds of microspheres exhibit a prolonged
residence time at the site of application and causes intimate contact with the
absorption site and produces better therapeutic action.
Magnetic microspheres
This kind of delivery system is very much important which localises the
drug to the disease site. In this larger amount of freely circulating drug can be
replaced by smaller amount of magnetically targeted drug. Magnetic carriers
receive magnetic responses to a magnetic field from incorporated materials that
are used for magnetic microspheres are chitosan, dextran etc.
The different type are
Therapeutic magnetic microspheres:
13
They are used to deliver chemotherapeutic agent to liver tumour. Drugs
like proteins and peptides can also be targeted through this system.
Diagnostic microspheres:
Can be used for imaging liver metastases and also can be used to
distinguish bowel loops from other abdominal structures by forming nano size
particles supramagnetic iron oxides.
Floating microspheres
In floating types the bulk density is less than the gastric fluid and so
remains buoyant in stomach without affecting gastric emptying rate. The drug is
released slowly at the desired rate, if the system is floating on gasteric contentand
increases gastric residence and increases fluctuation in plasma
concentration. Moreover it also reduces chances of striking and dose dumping.
One another way it produces prolonged therapeutic effect and therefore
reduces dosing frequencies. Drug (ketoprofen) given through this form.
Radioactive microspheres
Radio emobilisation therapy microspheres sized 10-30 nm are of larger
than capillaries and gets tapped in first capillary bed when they come across. They
are injected to the arteries that lead to tumour of interest. So all these conditions
radioactive microspheres deliver high radiation dose to the targeted areas without
damaging the normal surrounding tissues.
APPLICATION OF MICROSPHERES
Medical application
 Release of proteins, hormones and peptides over extended period of time.
 Gene therapy with DNA plasmids and also delivery of insulin.
 Vaccine delivery for treatment of diseases like hepatitis, influenza,
pertussis, ricin toxoid, diphtheria, birth control.
 Passive targeting of leaky tumour vessels, active targeting of tumour cells,
antigens, by intraarterial/ intravenous application.
 Tumour targeting with doxorubicin and also treatments of leishmaniasis.
14
 Magnetic microspheres can be used for stem cell extraction and bone
marrow purging.
 Used in isolation of antibodies, cell separation, and toxin extraction by
affinity chromatography.
 Used for various diagnostic tests for infectious diseases like bacterial, viral,
and fungal.
Radioactive microsphere’s application
 Can be used for radioembolisation of liver and spleen tumours.
 Used for radiosynvectomy of arthiritis joint, local radiotherapy,
interactivity treatement.
 Imaging of liver, spleen, bone marrow, lung etc and even imaging of
thrombus in deep vein thrombosis can be done.
Other applications
 Fluorescent microspheres can be used for membrane based technologies
for flow cytomettry, cell biology, microbiology, Fluorescent Linked
Immuno-Sorbent Assay.
 Yttrium 90 can be used for primary treatment of hepatocellular carcinoma
and also used for pretransplant management of HCC with promising
results.
PROCEDURE
A solution of albumin (1g in 25 ml) was prepared and drug (1g) was added
to the albumin solution. The contents were slowly added to a beaker containing
100ml of preheated (60ᵒC) liquid paraffin containing tween 80 as emulsifying
agent and stirred for 1 hr. The temperature was reduced to 40ᵒC for hadening
process and was maintained for 25min. The resulting microspheres were
stabilized using glutaraldehyde solution(25%w/v) for a period of 15min. The
15
microspheres were collected by decantation and washed with n-hexane and dried
at room temperature.
EVALUATION
Particle Size Analysis: Determined the average size of the particles using an
optical microscopic method.
Dissolution Study:
The study was carried out using Type-2 Paddle type USP apparatus. The set
condition was 900ml of 6.8pH phosphate buffer, at 50 rpm, 37ᵒC for 45 minutes,
5ml of samples were withdrawn at time intervals of 5, 15, 30, 45 minutes, which
was replaced by fresh equal volume of dissolution medium, the sample was
diluted suitably, assayed at 275nm by using UV-Visible spectroscopy. The
calibration curve was used to determine the drug concentration per ml. The
amount of drug release was calculated using calibration curve method.
Amount of drug release =
Percentage drug release =
𝑐𝑜𝑛𝑐.×𝑣𝑜𝑙.𝑜𝑓.𝑑𝑖𝑠𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝑚𝑒𝑑𝑖𝑢𝑚×𝑑𝑖𝑙 𝑓𝑎𝑐𝑡𝑜𝑟
1000
𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑟𝑒𝑙𝑒𝑎𝑠𝑒
𝑠𝑡𝑟𝑒𝑛𝑔𝑡ℎ
x 100
Determination of Drug Content:
100mg of drug loaded microsperes were added to 100ml of 6.8pH phosphate
buffer.Stirr the dispersion using magnetic stirrer for 3hrs.Filterthe dispersion
using whatmann filter paper and dilute it according to need(take 1ml dilute to
100ml) and measure the absorbance at 276nm.
Percentage Drug Entrapment (%DE)
Accurately weighed 100mg of microsphere were dissolved in 100ml PBS
pH 6.8. The solution was kept overnight and was filtered through whatman filter
0.45µm. The drug concentration was determined by UV spectrometer at
16
maximum wavelength of 276nm. The following equation was used to calculate
% drug entrapment:
% Drug Entrapment =
practical drug content
theoretical drug content
× 100
REPORT
 The formulation and evaluation of bovine serum albumin microspheres of
diclofenac sodium was prepared.
 The percentage drug release of diclofenac sodium microspheres was found
to be
REFERENCES
1. Leon Lachmann, Liebermann.H.A.Kaning JL, Theory and practice of
a. industrial pharmacy,3rd edition,420-428
2. S.P.Vyas, R.K.Khar, “Targeted and Controlled drug delivery”, novel
carrier system, CBS publishers and distributors, New Delhi, page no: 122
17
EXP.NO: 4
DATE:
FORMULATION AND EVALUATION OF DICLOFENAC GEL
AIM
To formulate and evaluate the diclofenac sodium gel by using natural polymer.
OBJECTIVE
To improve the patient compliance using newly developed diclofenac sodium gel
MATERIALS REQUIRED
APPARATUS: Digital weighing balance, beaker, standard flasks
CHEMICALS: Diclofenac sodium, sodium alginate, EDTA, potassium hydrogen
ortho phosphate, methyl paraben, propyl paraben, PEG 400
THEORY
The invitro permeation of drugs can be studied by trans diffusion cells. The franz
diffusion cells are made of glass with a contact area of 4.7cm2 with solubilizing
agent, the franz diffusion consist of donar compartment(A) and receptor
compartment(B). The membrane is mounted between two cells compartments.
The two cell compartments are held together with a clamp. The receptor
compartment has a volume of 37ml and is filled with diffusion medium, it is kept
at 37ᵒC by circulating water through an external water jacket. After 30 mins of
equilibrium of membrane with the receptor solution specific quantity of drug or
formulation , applied in the donar compartment is the covered with paraffin to
prevent the evaporation of solvent. The receptor solution is continuously stirred
by means of spinning bar magnet at 400rpm. 1ml samples are withdrawn from
the receptor compartment at various time intervals. The cells are refilled with
receptor solution to keep the release of receptor solution during experiment.
18
PROCEDURE
Preparation of Gel
Potassium dihydrogen phosphate, diclofenac sodium, EDTA, Sodium Alginate
were dissolved in water under agitation with mechanical stirrer. Methyl paraben,
propyl paraben, PEG 400 were added to it under continuous stirring, polymer was
slowly springed on the surface of purified water for uniform distribution. The gel
were buffered at 7.4 ±0.2
EVALUATION
pH: The pH is determined by 2.5g of gel was dispersed in 25ml of purified water
and pH is measured by pH meter.
Rheological study: Rheological study using Brookfield viscometer.
Diffusion study: Diffusion studies were carried out using Franz diffusion cell.
Accurately weighed 0.3g of gel was spread uniformly on a dialysis membrane
which was in contact with receptor medium. The receptor medium stirred
continuously at 20 rpm to stimulate blinking action of eyelids. Samples were
withdrawn at periodic intervals. The drug content was analysed using UV
spectrophotometer at 271nm, against reference standards using distilled water as
blank.
REPORT
The percentaqge amount of drug diffused of diclofenac gel was found to be
REFERENCES
1. S.P.Vyas, R.K.Khar, “Targeted and Controlled drug delivery”, novel
carrier system, CBS publishers and distributors, New Delhi, page no: 122
2. N.K. Jain “Pharmaceutical product development” CBS publishers and
distributors, New Delhi, page no: 182.
3. Encyclopedia of pharmaceutical technology, 3rd edition vol-3 page no: 567
19
EXP.NO: 5
DATE:
FORMULATION AND COMPARITIVE EVALUATION OF
SUSTAINED RELEASE DICLOFENAC SODIUM MATRIX TABLETS
AIM
To formulate and comparative evaluation of diclofenac sodium SR tablets.
OBJECTIVE
To develop the diclofenac sodium tablets and compare with commercial
diclofenac sodium SR tablet. To produce quality SR tablets.
MATERIALS REQUIRED
APPARATUS: Mortar and pestle, beaker, sieve no 10, tablet punching machine,
hot air oven.
CHEMICALS: Diclofenac sodium, Hydroxy propyl methyl cellulose, avicel,
polyvinyl pyrollidine, isopropyl alcohol, magnesium stearate, talc, Voveran SR
THEORY
Diclofenac sodium is one of the drugs of choice to treat arthritis because
of its potential anti- inflammatory and analgesic activity and this is the only
approved NSAID available for parenteral delivery. Because of shorter biological
half-life, diclofenac sodium should be given frequently to maintain its therapeutic
activity.
It also has high percentage of protein binding and it undergoes presystemic
metabolism. To overcome these problems, many authors developed sustained
release formulations with an intention to maintain effective diclofenac
concentration for prolonged period.
20
Tablets are solid dosage forms containing one or more drugs with or
without excipients, prepared by compression. It provides greatest dose precision
and least content variability. Inert materials employed in addition to active
ingredients are collectively called tablet additives.
They include
1. DILUENTS: are fillers designed to make up the required weight of the tablet.
Eg: lactose, inorganic dicalcium salts microcrystalline cellulose etc.
2. BINDING AGENTS: are added in dry or in liquid form to obtain cohesive
mass for direct compression. Eg: Cellulose derivatives, gelatin solution, glucose
syrup, tragacanth mucilage etc.
3. DISINTEGRATING AGENTS: are added to facilitate breakup of the tablet
when in contact with gastrointestinal fluids. Eg: dry starch, starch derivatives,
clays, cellulose, cellulose derivatives, alginates
4. ADSORBENTS: included when formulation contains liquids, volatile oils etc.
5. ANTIFRICTIONAL AGENTS: enhance flow properties. Eg : talc, corn
starch, silica derivatives etc.
The usual methods of formulation include wet granulation, dry granulation
and direct compression.
Tablets are evaluated for their general appearance, hardness, friability,
drug content, release, weight variation, dissolution and disintegration properties
The most widely used and most general method of tablet preparation is the wet
granulation method. The active ingredient, diluent and disintegrents are mixed or
blended well. For large-scale production twin shell blender, double cone blender,
planatory mixer, sigma blade mixer, ribbon mixer etc. are commonly used.
Solutions of the binding agent are added to the mixed powder with stirring. The
powder mass is wetted with the binding solution until the mass has the
consistency of damp snow. If the granulation is over wetted the granules will be
hard, if not wetted sufficiently, the resulting granules will be too soft, breaking
down during lubrication. The wet mass is forced through a 6 or 8 mesh (Mesh no.
21
is the number of wires passing through an inch) screen or several mills can be
used .Moist materials from wet milling steps is placed on large trays and placed
in drying chambers with a circulating air current and thermostable heat controller.
Commonly used dryers are tray dryer, fluidized bed dryer. After drying, the
granulation is reduced in particle size by passing smaller mesh screen.
The screen size depends on the diameter of the punch as follows:
Tablet upto 3/16 in diameter ----------------------- 20 mesh
Tablet upto 7/32 into 5/16 in diameter ------------16 mesh
Tablet upto11/32 into13/32 in diameter -----------14 mesh
Tablet upto 7/16 in and more -----------------------16 mesh
After drying granulation, the lubricant or glidants is added as fine powder to
promote flow of granules. These granules then compressed to get tablet
PROCEDURE
Weigh the required quantity of diclofenac sodium and mixed it with HPMC and
avicel. Prepared the granules using 20% polyvinyl pyrrolidine in isopropyl
alcohol. Passed the dried granules through sieve no 10 and dried at 40ᵒC for 45
minutes. Lubricate the granules with the suitable lubricant and glidant and
compress in a single punching machine. Evaluation of the compressed tablet were
performed.
FORMULA:
Sl.no
Ingredients
Quantity for 1
Quantity for 50
Tablet(mg)
tablets(g)
1
Diclofenac sodium
100
5
2
HPMC
40
2
3
MCC
60
3
22
4
Polyvinyl pyrollidine
10
500
5
Mag.stearate
2%
2%
6
Talc (purified)
2%
2%
EVALUATION
1. Hardness Test: Tablet hardness was measured using Monsanto hardness test
apparatus.
2. Weight Variation Test: 20 tablets are weighed individually. Calculated the
average weight and individual weight are compared with the average weight.
3. Friability Test: Friability is a measure of mechanical strength of the tablet. If
a tablet has more friability it may not remain intact during packaging, transport
or handling. Roche friabilator is used to determine the friability by following
procedure. Pre weighed tablets are placed in the friabilator. Friabilator consist of
a plastic chamber that revolves at 25 rpm, dropping those tablets at a distance of
6 inches with each revolution. The tablets are rotated in the friabilator for at least
4 minutes. At the end of test tablets are dusted and reweighed; the loss in the
weight of tablet is the measure of friability and is expressed in percentage as:
% Friability = 1‐ (loss in weight / Initial weight) X 100
4. Assay: 20 tablets are powdered and weighed. A quantity of powder equivalent
to about 0.15g of paracetamol are accurately weighed and added 50ml of 0.1M
sodium hydroxide, diluted with 100ml of water, and shaked for 15 mins and
added sufficient water to produce 250ml. They are mixed filtered and diluted
10ml of the filtrate to 100ml with water. To 10ml of resulting solution 10ml of
0.1M sodium hydroxide are added and diluted to 100ml with water and mixed.
The absorbance of the resulting solution at the maximum at about 257nm were
measured by using UV-Visible spectroscopy.
23
5. Disintegration Study
Experimental conditions were:
Medium: water
Speed: 30cycles/minute
Temperature: 37±0.5ᵒC
One tablet was added into each of the 6 tubes of the apparatus and the assembly
was suspended in a beaker containing water and time required to disintegrate each
tablet was noted. From this average disintegration time was determined.
6. Dissolution Study: The study was carried out using Type-2 Paddle type USP
apparatus. The set condition was 900ml of 0.1M hydrochloric acid, at 50 rpm,
37ᵒC for 45 minutes, 5ml of samples were withdrawn at time intervals of 5, 15,
30, 45 minutes, which was replaced by fresh equal volume of dissolution medium,
the sample was diluted suitably, assayed at 249nm by using UV-Visible
spectroscopy. The calibration curve was used to determine the drug concentration
per ml. The amount of drug release was calculated using calibration curve
method.
Amount of drug release =
Percentage drug release =
𝑐𝑜𝑛𝑐.×𝑣𝑜𝑙.𝑜𝑓.𝑑𝑖𝑠𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝑚𝑒𝑑𝑖𝑢𝑚×𝑑𝑖𝑙 𝑓𝑎𝑐𝑡𝑜𝑟
1000
𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑟𝑒𝑙𝑒𝑎𝑠𝑒
𝑠𝑡𝑟𝑒𝑛𝑔𝑡ℎ
x 100
REPORT
Matrix tablets of diclofenac sodium was formulated and invitro release rate
was studied and compared with marketed coated formulation of diclofenac
sodium.
REFERENCES
1. Lachman L Lieberman H.A, Kanig J.L, The Theory and Practice of Industrial
Pharmacy, 3rd edition
2. Michael E.Aulton. Pharmaceutics, The science of Dosage form design.
24
EXP.NO: 6
DATE:
EFFECT OF DIFFERENT BINDING AGENTS ON THE PROPERTIES
OF PARACETAMOL TABLETS
AIM
To study the influence of various binding agents on the properties of
paracetamol tablets.
OBJECTIVE
To develop the paracetamol tablets by using different binding agents for
selection of effective binder
MATEIALS REQUIRED
APPARATUS: Mortar and pestle, beaker, sieve no 10, tablet punching machine,
hot air oven.
CHEMICALS: Paracetamol, Hydroxy propyl methyl cellulose, avicel, polyvinyl
pyrollidine, isopropyl alcohol, magnesium stearate, talc, starch, acacia, gelatin
THEORY
Paracetamol has analgesic and antipyretic properties but it has no useful
anti-inflammatory properties. Paracetamol is readily absorbed from the
gastrointestinal tract. Paracetamol is categorized under BCS classification II
Tablets are solid dosage forms containing one or more drugs with or
without excipients, prepared by compression. It provides greatest dose precision
and least content variability. Inert materials employed in addition to active
ingredients are collectively called tablet additives.
They include
25
1. DILUENTS: are fillers designed to make up the required weight of the tablet.
Eg: lactose, inorganic dicalcium salts microcrystalline cellulose etc.
BINDING AGENTS: are added in dry or in liquid form to obtain cohesive mass
for direct compression. Eg: Cellulose derivatives, gelatin solution, glucose
syrup, tragacanth mucilage etc.
3. DISINTEGRATING AGENTS: are added to facilitate breakup of the tablet
when in contact with gastrointestinal fluids. Eg: dry starch, starch derivatives,
clays, cellulose, cellulose derivatives, alginates
4. ADSORBENTS: included when formulation contains liquids, volatile oils etc.
5. ANTIFRICTIONAL AGENTS: enhance flow properties. Eg : talc, corn starch,
silica derivatives etc.
The usual methods of formulation include wet granulation, dry granulation
and direct compression. The most widely used and most general method of tablet
preparation is the wet granulation method. The active ingredient, diluent and
disintegrents are mixed or blended well. Solutions of the binding agent are added
to the mixed powder with stirring. The powder mass is wetted with the binding
solution until the mass has the consistency of damp snow. If the granulation is
over wetted the granules will be hard, if not wetted sufficiently, the resulting
granules will be too soft, breaking down during lubrication. The wet mass is
forced through a 6 or 8 mesh (Mesh no. is the number of wires passing through
an inch) screen or several mills can be used .Moist materials from wet milling
steps is placed on large trays and placed in drying chambers with a circulating air
current and thermostable heat controller. Commonly used dryers are tray dryer,
fluidized bed dryer. After drying, the granulation is reduced in particle size by
passing smaller mesh screen.
After drying granulation, the lubricant or glidants is added as fine powder to
promote flow of granules. These granules then compressed to get tablet.
Binders or adhesives are materials that are added either dry or as liquid
form during wet granulation to form granules or to promote cohesive compact for
26
directly compressed tablets. Tablet binders are the substances which are used to
cause adhesion of powder particle in tablet granulation.
The different binders in common use include starch mucilage, acacia, and
tragacanth solution (10-20%), gelatin solution, cellulose derivative, polyvinyyl
pyrrollidone.
PROCEDURE
Five different binding agents were used and five different formulations were
made
F1 – 5% starch as binding agent
F2 – 5% HPMC in water as binding agent
F3 – 10% acacia as binding agent
F4 – 10% gelatin as binding agent
F5 – 10% polyvinyl pyrrollidone as binding agent
The different formulations were granulated by passing through no 10 mesh size
sieve. The granules were then dried at 55ᵒC. After drying, dry screening of
granules was done using no 14 size sieves. This was followed by addition of
remaining half of the starch, talc, and magnesium stearate. These were then
compressed to form tablets on flat rounded punches on a 10 station rotary tablet
machine.
EVALUATION OF TABLETS
1. Hardness Test: Tablet hardness was measured using Monsanto hardness test
apparatus.
2. Weight Variation Test: 20 tablets are weighed individually. Calculated the
average weight and individual weight are compared with the average weight.
3. Friability Test: Friability is a measure of mechanical strength of the tablet. If
a tablet has more friability it may not remain intact during packaging, transport
or handling. Roche friabilator is used to determine the friability by following
27
procedure. Pre weighed tablets are placed in the friabilator. Friabilator consist of
a plastic chamber that revolves at 25 rpm, dropping those tablets at a distance of
6 inches with each revolution. The tablets are rotated in the friabilator for at least
4 minutes. At the end of test tablets are dusted and reweighed; the loss in the
weight of tablet is the measure of friability and is expressed in percentage as:
% Friability = 1‐ (loss in weight / Initial weight) X 100
4. Assay: 20 tablets are powdered and weighed. A quantity of powder equivalent
to about 0.15g of paracetamol are accurately weighed and added 50ml of 0.1M
sodium hydroxide, diluted with 100ml of water, and shaked for 15 mins and
added sufficient water to produce 250ml. They are mixed filtered and diluted
10ml of the filtrate to 100ml with water. To 10ml of resulting solution 10ml of
0.1M sodium hydroxide are added and diluted to 100ml with water and mixed.
The absorbance of the resulting solution at the maximum at about 257nm were
measured by using UV-Visible spectroscopy.
5. Disintegration Study
Experimental conditions were:
Medium: water
Speed: 30cycles/minute
Temperature: 37±0.5ᵒC
One tablet was added into each of the 6 tubes of the apparatus and the assembly
was suspended in a beaker containing water and time required to disintegrate each
tablet was noted. From this average disintegration time was determined.
6. Dissolution Study: The study was carried out using Type-2 Paddle type USP
apparatus. The set condition was 900ml of 6.8pH phosphate buffer, at 50 rpm,
37ᵒC for 45 minutes, 5ml of samples were withdrawn at time intervals of 5, 15,
30, 45 minutes, which was replaced by fresh equal volume of dissolution medium,
28
the sample was diluted suitably, assayed at 249nm by using UV-Visible
spectroscopy. The calibration curve was used to determine the drug concentration
per ml. The amount of drug release was calculated using calibration curve
method.
Amount of drug release =
Percentage drug release =
𝑐𝑜𝑛𝑐.×𝑣𝑜𝑙.𝑜𝑓.𝑑𝑖𝑠𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝑚𝑒𝑑𝑖𝑢𝑚×𝑑𝑖𝑙 𝑓𝑎𝑐𝑡𝑜𝑟
1000
𝑎𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑟𝑒𝑙𝑒𝑎𝑠𝑒
𝑠𝑡𝑟𝑒𝑛𝑔𝑡ℎ
x 100
REPORT:
Paracetamol tablets using 5% starch, 5% HPMC, 10% Gelatin, 10% polyvinyl
pyrrollidone as binding agents were prepared and evaluated each of the
formulation.
REFERENCE:
1. Lachman L Lieberman H.A, Kanig J.L, The Theory and Practice of Industrial
Pharmacy, 3rd edition
2. Michael E.Aulton. Pharmaceutics, The science of Dosage form design.
29
EXP.NO:7
DATE:
PREPARATION AND EVALUATION OF DICLOFENAC SODIUM
GELS USING DIFFERENT GEL BASES
AIM
To prepare and evaluate diclofenac gels using different gel bases
(Carbopol, HPMC, sodium alginate) and comparison with markedly available
Diclofenac sodium B.P.
OBJECTIVE
To develop the different diclofenac gels using different gel bases and to
study the comparison with markedly available diclofenac gel.
MATERIALS REQUIRED
APPARATUS: Beaker, measuring cylinder, digital weighing balance, mortar and
pestle.
CHEMICALS: Diclofenac sodium, Carbopol, HPMC, sodium alginate, glycerin,
dimethyl formamide.
THEORY
Topical drug delivery systems are the formulations that are intended to
deliver drugs locally rather than systemically. Such delivery systems may be
formulated for ophthalmic, otic, vaginal, or oral (mouth and throat use).
A topical product is applied to the skin as a thin film with or without
rubbing action, such that no substantial mass remains on the skin following
application.
A topical product should have the following properties
 It should be therapeutically effective and perform its intended action
30
 The loss of potency of product with time should be within limits. The
product should also have microbiological stability throughout its shelf life.
 The product should exhibit physicochemical stability with respect to color,
odour, pH, viscosity, etc. over its shelf life.
 The product should have aesthetic appeal, spread easily and adhere to skin.
 The product should be easy to manufacture and scale up with current
technology.
 The product should be consumer friendly and in a marketable package.
They include emulsions and micro emulsions, ointments, gels, aerosols,
powders, solutions etc.
Gels are semisolid systems consisting of a suspension made up of small
inorganic particles or large organic molecules interpenetrated by liquid. Small
organic molecules form a three dimensional network throughout the gel structure.
Large organic molecules that are either natural or synthetic polymers on the other
hand exist as randomly coiled chains that entangle with each other to form a gel
structure.
Some of the commonly used polymers are:
1. Natural gums: alginates, pectin, chitosan
2. Cellulose derivatives: NaCMC, HPMC, HPC
3. Colloidal solids: silica, clays, microcrystalline cellulose
4. Thermo reversible polymers: poloxamer
5. Hydrogels: PVA,PVP
Based on the type of gelling agent, it is of two types:
1. Hydrophobic gels: the bases of hydrophobic gels (oleo gels) usually
consists of liquid paraffin with polyethylene or fatty oils gelled with
colloidal silica or aluminum or zinc soaps
2. Hydrophilic gels: the bases of hydrophilic gels (hydrogels) usually
consists of water, glycerol, or polypropylene glycol gelled with suitable
31
gelling agents such as tragacanth, starch, cellulose derivatives and magnesium
aluminium silicates.
The viscosity of gels decreases upon application of shear (such as
squeezing from a tube) or with an increase in temperature. Gels may exhibit
Newtonian, plastic, or pseudoplastic behavior depending on the nature of the
gelling agent.
Some commonly used excipients in gel based formulation are:
 Preservatives: alcohols, ascorbic acid
 Anti-oxidants: ascorbic acid, sodiumbisulphite
 Emollients and moisturizers: glycerin, sorbitol
 Buffering agents: triethanolamine, lactic acid
 Penetration enhancers: propylene glycol, salicylic acid, alcohols
 Solubilizing agents: benzalkonium chloride, benzethonium chloride
PROCEDURE
Diclofenac sodium using HPMC as polymer:
2g of HPMC was taken and soaked in water for 24 hrs.1ml of glycerin was
added and triturated well. 0.5% solution of drug in minimum quantity of DMF
was added to the mortar with slow trituration to get homogenous gel to 20g.
Diclofenac sodium using Carbopol as polymer
FORMULA:
Carbopol 934(carbomer)- 2g
Triethanolamine: 1.65ml
Parabens-0.2g
Water upto 100ml
2g of Carbopol 934 polymer was taken in a mortar and water was
added.this was soaked for half an hour. The drug was dissolved in ethanol and
added to mortar. The pH of the above mixture was adjusted to 7.4 with
32
triethanolamine and triturated well to get a homogenous dispersion of drug with
gel.
Diclofenac sodium using sodium alginate as polymer
FORMULA:
Sodium alginate:10g
Glycerin: 10g
Methyl hydroxyl benzoate: 0.2g
Calcium gluconate: 0.5g
Water upto 100ml
Minimum quantity of DMF was added to the mortar with slow trituration to get
homogenous gel to 20g
EVALUATION
pH
The pH is determined by 2.5g of gel was dispersed in 25ml of purified water and
pH is measured by pH meter.
Invitro drug release
Invitro release studies were carried out using franz diffusion cell. Accurately
weighed 0.3g of gel was spread uniformly on a dialysis membrane which was in
contact with receptor medium. The receptor medium stirred continuously at 20
rpm to stimulate blinking action of eyelids. Samples were withdrawn at
appropriate intervals and the samples were analyzed using UV spectrophotometer
at 271nm. The drug content was estimated using calibration curve of diclofenac
sodium.
33
REPORT
The gels of diclofenac sodium using 5% HPMC, 1% Carbopol, sodium
alginate were prepared and evaluated. Drug release from diclofenac gel BP and
prepared gels were compared using Franz diffusion apparatus.
The drug release from
Diclofenac gel B.P:
Diclofenac sodium gel using sodium alginate:
Diclofenac sodium gel using HPMC:
Diclofenac sodium gel using Carbopol:
REFERENCES
1. D.M.Brahmankar, Sunil.B.Jaiswal. Biopharmaceutics and Pharmacokinetics
A Treatise, Page no: 66-67
2. Cooper And Gunn’s dispensing For Pharmaceutical Students, 42nd Edition
3. Indian journal of pharmaceutical science; January-February 2008
4. Indian journal of pharmaceutical education and research January-March 2008
34
EXP.NO:8
DATE:
FORMULATION AND EVALUATION OF TRANSDERMAL PATCHES
OF DICLOFENAC POTASSIUM
AIM
To formulate and evaluate transdermal patches of diclofenac potassium
(model drug)
OBJECTIVE
To develop the transdermal patches of diclofenac potassium.
MATERIALS REQUIRED
APPARATUS: Beaker, standard flask, petridish, digital weighing balance
CHEMICALS: Diclofenac potassium, propylene glycol, span 80, polymer
solution, ethyl cellulose, methyl cellulose, polyvinyl pyrrolidine, chloroform
THEORY
Transdermal drug delivery systems are designed to provide continuous
delivery of drug directly into the systemic circulation. It provides several benefits
including avoidance of first pass effect and also to get a constant drug delivery
over a long period.
Transdermal
drug
delivery
systems
are
topically
administered
medicaments in the form of patches (or semisolids) that deliver drugs for systemic
effects at a predetermined and controlled rate. Some of the advantages of these
systems over other controlled-release formulations are1. Avoidance of the first pass effect
2. Stable and controlled blood level
3. Comparable characteristics with intravenous infusion
4. Ease of termination of drug action, if necessary
35
5. Long duration of action(ranging from a few hours to one week)
6. No interference with gastric and intestinal fluids.
The route is unsuitable when
1. Drug dose is large
2. Drug has large molecular size (makes absorption difficult; should ideally
be below 800-1000 Daltons.)
3. Drug is skin sensitizing and irritating
4. Drug is metabolized in skin
5. Drug undergoes protein binding in skin
Drugs which degrade into gastro intestinal tract, inactivated by hepatic first
pass effect, drugs which are administered for a long period of time and causing
adverse effects to non-targeted tissues can be formulated as TDDS. Drugs like
propranolol hydrochloride are ideal candidate for TDDS. In this formulation
diclofenac potassium is used as model drug.
PROCEDURE
Weighed the calculated quantities of ethyl cellulose, methyl cellulose and
polyvinyl pyrrolidine. Dissolve the three polymers in the required quantity of
chloroform. Added span 80 and propylene glycol to the solution of polymer.
Stirred well added the drug to the solution and mixed well. This solution was
poured into a glass petridish containing mercury. Allowed it to dry at room
temperature for about 48 hours. When the film was formed, removed it and
checked for any imperfections and air bubbles. Noted down the total weight and
the diameter of the film.
EVALUATION OF TRANSSDERMAL PATCHES
Evaluation of transdermal patches includes various parameters like peel
adhesion, tacking property, shear strength, invitro drug release, invitro release
pattern and cutaneous toxicological studies. Evaluation of transdermal system
includes
36
Determination of folding endurance
Folding endurance of the patch is determined by folding one patch
repeatedly at one point or at same place till it breaks and noting down the number
of times it resist the folding.
Determination of drug content
Put the square patch in 10ml of 6.8pH phosphate buffer, added and stirred
in a magnetic stirrer for 12 hrs at constant rpm. Centrifuged the solution at 2000
rpm. Collect the supernatant and diluted it properly and measure the absorbance
at 273nm using 6.8 pH phosphate buffer as blank. Calculated the drug loading
efficiency of square shaped film.
Invitro diffusion study
Invitro release studies were carried out using Franz diffusion cell.
Transdermal patch was soaked in buffer and placed above the membrane. The
receptor medium (6.8 pH phosphate buffer) stirred continuously at 20 rpm.
Samples were withdrawn at periodic intervals of 15, 30,45,60,90,120 minutes.
The drug content was analyzed using UV spectrophotometer at 275nm.
REPORT
Transdermal patches of diclofenac potassium was prepared and evaluation
tests were done. The result are as follows
Average weight=
Average thickness=
Folding endurance=
Cumulative percent of drug release in 24 hrs. =
REFERENCES
1. Indian Journal Of Pharmaceutical Sciences, July-August 2009
2. S.P. Vyas, Roop K Khar, Controlled Drug Delivery-Concepts And
Advances
37
EXP.NO:9
DATE:
FORMULATION AND EVALUATION OF POLYMER OCULAR FILM
CONTAINING DICLOFENAC POTASSIUM USING ETHYL
CELLULOSE
AIM
To formulate and evaluate a polymeric ocular film of diclofenac potassium
using ethyl cellulose
OBJECTIVE
To develop the polymeric ocular film of diclofenac potassium
MATERIALS REQUIRED:
APPARATUS: Beaker, standard flask, petridish, digital weighing balance
CHEMICALS: Diclofenac potassium, ethyl cellulose, isopropyl alcohol
THEORY
The novel ocular drug delivery systems have been formulated with two
main objectives, bioavailability and controlled release. Absorption of ophthalmic
drugs across the corneal membrane is a diffusion process and depends upon
physicochemical properties of penetrating molecule and drainage and output of
tears. A number of ocular drug delivery systems have been developed for
providing zero order release. The best known system is ocular insert or ocusert.
PROCEDURE
Weighed 100mg of drug and added it in a clean beaker. Weighed and
transferred 1gm of ethyl cellulose and added it to previous beaker containing
drug. Mixed both the drug and polymer in 25ml of isopropyl alcohol using a
magnetic stirrer. Allowed the mixing to occur for atleast 20 minutes to get a
38
homogenous mass. Passed the polymer mixture to a rectangular mould. Kept the
mold in hot air oven at 60ᵒ for half an hour. After complete evaporation of solvent
from film, it was taken out from mould and cut into 1x1cm squares. Invitro release
of the drug from the ocular film was determined by the procedure given below.
Invitro evaluation
Invitro release studies were carried out using Franz diffusion cell. The polymeric
ocular film was soaked in buffer and placed above the membrane. The receptor
medium (6.8 pH phosphate buffer) stirred continuously at 20 rpm. Samples were
withdrawn at periodic intervals of 15, 30,45,60,90,120 minutes. The drug content
was analyzed using UV spectrophotometer at 275nm
Determination of drug content
Put the square patch in 10ml of 6.8pH phosphate buffer, added and stirred
in a magnetic stirrer for 12 hrs at constant rpm. Centrifuged the solution at 2000
rpm. Collect the supernatant and diluted it properly and measure the absorbance
at 273nm using 6.8 pH phosphate buffer as blank. Calculated the drug loading
efficiency of square shaped film.
REPORT
Ocular film containing diclofenac potassium using ethyl cellulose polymer
was prepared and evaluated. The result are as follows
The drug content of 1cmx 1cm film was found to be
Cumulative percentage of drug released was found to be
within
The T50% of ocular film was found to be
REFERENCES
1. S.P. Vyas, Roop K Khar, Controlled Drug Delivery-Concepts And Advances
2. D.M.Brahmankar, Sunil.B.Jaiswal. Biopharmaceutics and Pharmacokinetics
A Treatise, First edition.
39
EXP.NO:10
DATE:
MICROENCAOSULATION OF DICLOFENAC SODIUM BY
TEMPERATURE CHANGE METHOD
AIM
To formulate and evaluate diclofenac microcapsules with ethyl cellulose by
temperature change method
OBJECTIVE
To develop the microcapsules of diclofenac sodium and to study the drug release
MATERIALS REQUIRED:
APPARATUS: Beaker, standard flask, digital weighing balance
CHEMICALS: Ethyl cellulose, cyclohexane, diclofenac potassium
THEORY
Microencapsulation is a mean of applying relatively thin coating to small
particles of solids or droplets of liquids or droplets of dispersions.
The application of microencapsulation include:
1. Sustained release
2. Taste masking
3. Multilayered tablets
4. For newer formulation concepts of creams aerosols etc.
In this experiment the microcapsules are prepared by coacervation phase
separation which consists of following three steps under continuous agitation.
1. Formulation of liquid manufacturing vehicle phase, core material phase,
coating material phase. In the temperature change method the polymer
ethyl cellulose which is insoluble in cyclohexane at room temperature. But
it is soluble at elevated temperature. The polymer is dispersed and the
40
mixture is heated to boiling point. The core material (drug) is dispersed in
the polymer solution. Allow the mixture to cool with continuous stirring
which will subsequently allow the phase separation process to occur.
2. This step consists of depositing the liquid polymer coating upon the core
material by control physical mixing.
3. This step involves rigidizing the coating by thermal or crosslinking or
desolvation technique.
PROCEDURE
Disperse ethyl cellulose in cyclohexane to yield polymer solution of 2% by
weight (2gm in 100ml of cyclohexane). Heat the mixture to its boiling point to
form homogenous polymer solution. Disperse the drug in polymer solution by
stirring at a coating to core material ratio of (2:1) (polymer: drug). Allow the
mixture to cool with continuous stirring to induce coacervation phase separation.
Collect the micro capsules after solidification.
EVALUATION
Invitro dissolution study
100mg of prepared microcapsules was weighed and placed in dissolution
apparatus. 900ml of pH 6.8 phosphate buffer was used as dissolution medium.
The dissolution study was performed at 50 rpm for 3 hr. 5ml of samples were
withdrawn at time interval of 15,30,45,60minutes, 1, 2, 3, 4, 5, 6hours. After each
withdrawal an equivalent amount of fresh dissolution medium was replaced.
Temperature was maintained at 37ᵒC. the absorbance of withdrawn sample after
filtration was measured at 275nm using UV spectrophotometer. The results were
plotted in a graph.
41
REPORT
Microcapsule of diclofenac sodium was formulated from ethyl cellulose by
temperature change method and the invitro dissolution testing was done. The
results are as follows
Cumulative percent drug released was found to be
REFERENCES
1. Leon Lachmann, Liebermann.H.A.Kaning JL, Theory and practice of
industrial pharmacy,3rd edition,420-428
2. S.P.Vyas, R.K.Khar, “Targeted and Controlled drug delivery”, novel
carrier system, CBS publishers and distributors, New Delhi, page no: 122
42
EXP.NO:11
DATE:
FORMULATION AND EVALUATION OF DICLOFENAC POTASSIUM
SOLID DISPERSION BY MELT METHOD
AIM
To formulate solid dispersion of diclofenac potassium with urea as carrier in
different ratio by melt method and to evaluate and compare the solubility and the
release characteristic
OBJECTIVE
To develop the solid dispersion of diclofenac potassium with urea as carrier and
to study the solubility and release characteristics.
MATERIALS REQUIRED
APPARATUS: Beaker, standard flask, digital weighing balance, petridish, china
dish
CHEMICALS: Diclofenac potassium, urea
THEORY
Solid dispersion technology is the science of dispersing more active ingredient is
an inert matrix in the solid state in order to achieve increase dissolution rate,
sustained release of drug altered solid state properties enhance the release of drug
from ointments, suppository base etc and solubility and stability. Most of the
drugs are positively absorbed and their rate of absorption depends upon the
gradient in each case. By increasing the dissolution rate in GIT ,the rate of
dissolution is increased as long as dissolution rate is still the rate limiting step.
Various carriers have been used in the formulation of solid dispersion which can
facilitate in improving the dissolution rate of poorly soluble drug to improve
better bioavailability
43
E.g.:- Dextrose, citric acid, urea, polyvinyl pyrrolidine glycol, poloxamers-188,
tween, spans, cyclodextrin etc.
Common preparation techniques of solid dispersion is
1. Solvent evaporation technique
2. Melting method
3. Kneading
4. Melting solvent method
5. Spray drying
6. Lipophilisation technique
7. Melt agglomeration process
Method of preparation of solid dispersion of diclofenac potassium using urea
as carrier by melt method
In melt method the physical mixture of drug and water soluble carrier was heated
to melt and the molten mixture was then cooled and then solidified and mass
crushed pulverized and sieved. The melting point of a binary system depends on
its composition and proper manipulation of drug carrier ratio. Decomposition
should be avoided due to fusion time and rate of cooling. Solid dispersion of drug
like Carbamazepine, Indomethacin, Piroxicam, Oxyzepam, Norfloxacin,
Paracetamol etc. sho0ws improved dissolution rate and availability of drugs.
PROCEDURE
Diclofenac potassium and urea were weighed separately in different ratio
1:1, 1:2, 1:3, urea was then taken in a china dish and heated to form a molten
mass to which the drug was added and melted. The molten mass was then cooled
suddenly, pulverized and sieved through sieve number 85. The product was
compared .a quantity equivalent to 200mg of drug was used for invitro dissolution
study.
44
EVALUATION
DETERMINATION OF DRUG LOADING OF SOLID DISPERSION
Transfer 200mg prepared solid dispersion of drug using urea(theoretically
equivalent to mg of diclofenac potassium) in to 100 ml of phosphate buffer of pH
6.8.Stir the dispersion using a magnetic stirrer for 3 hours Filter the dispersion,
dilute it to 10 times and measure the absorbance at 275nm.
Drug content =
𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 ×𝑑𝑖𝑙𝑢𝑡𝑖𝑜𝑛 𝑓𝑎𝑐𝑡𝑜𝑟×𝑣𝑜𝑙 𝑜𝑓 𝑑𝑖𝑠𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 𝑚𝑒𝑑𝑖𝑢𝑚
1000
SOLUBILITY TEST
Take 10ml of distilled water, keep and adding a quantity of solid
dispersion, each from 1:1 ratio, 1:2 ratio, 1:3 ratio until saturation level occurs
( until visible residue of solid dispersion occur)
INVITRO DISSOLUTION STUDY
100mg solid dispersion were weighed and placed in dissolution apparatus.
900ml of 6.8Ph phosphate buffer was used as dissolution medium. The
dissolution study was performed at 50 rpm for 6 hrs. 5 ml of samples were
withdrawn at time interval of 5, 10, 15, 30, 45, 60, 90 minutes and after each
withdrawal an equivalent amount of fresh dissolution medium was replaced.
Temperature was maintained at 370c .The absorbance of withdrawn sample after
filtration was measured at 276nm using UVspectrometer. The result were plotted
in graph.
REPORT
Solid dispersion of diclofenac potassium were formulated using urea as carrier in
different drug: carrier ratios 1:1, 1:2, 1:3; solubility and invitro dissolution of each
formulation were compared. It has been observed that there is aa proportional
increase in the solubility and rate of dissolution with the increase in the ratio of
carrier.
45
REFERENCES
1. Indian journal of pharmaceutical science; January-February 2008
2. Indian journal of pharmaceutical education and research January-March
2008
46
EXP.NO:12
DATE:
FORMULATION AND EVALUATION OF MAGNESIUM HYDROXIDE
ANTACID SUSPENSION
AIM
To formulate and evaluate magnesium hydroxide antacid suspension
OBJECTIVE
To develop the antacid suspension of magnesium hydroxide and to study their
acid neutralizing capacity
MATERIALS REQUIRED
APPARATUS: Beaker, standard flask, digital weighing balance, measuring
cylinder, mortar and pestle
CHEMICALS: Magnesium hydroxide, tragacanth, Sodium carboxyl methyl
cellulose
THEORY
A Pharmaceutical suspension is a coarse dispersion in which internal phase
(therapeutically active ingredient) is dispersed uniformly throughout the external
phase. The internal phase consisting of insoluble solid particles having a range of
size(0.5 to 5 microns) which is maintained uniformly throughout the suspending
vehicle with aid of single or combination of suspending agent.
The external phase (suspending medium) is generally aqueous in some instance,
may be an organic or oily liquid for non-oral use.
Some pharmaceutical suspensions:
 Antacid oral suspensions
 Antibacterial oral suspension
47
 Dry powders for oral suspension (antibiotic)
 Analgesic oral suspension
 Anti-helminthic oral suspension
 Anticonvulsant oral suspension
 Antifungal oral suspension
Since all suspension systems separate on standing, the formulator’s primary
concern is to decrease the rate of setting and permit easy re-suspend ability of any
settled particulate matter.
Suspension may be formulated as aggregated (open network aggregate) systems
or dispersed systems
When suspension particles are aggregated on an open network, a surfactant
is added to decrease the interfacial tension between particles. In dispersed
systems, apart from adding an agent to decrease interfacial tension, a viscosity
imparting agent is added to keep the particles in the suspend state. Sweeteners
and flavors are added to impart pleasant taste as the state of suspension product
has a great influence on consumer acceptance of the product. Parabens are added
as preservatives, and at a concentrations used here, they impart a numbing after
taste to the tongue, especially in the presence of peppermint flavor. The rate of
drug dissolution and bioavailability of antacid depends on physical features like
dispersability, particle size and polymorphism.
Antacids greatly differ in acid neutralizing capacity (ANC), which is
defined as the number of milli equivalents (meq) of a 1N solution of HCl that can
be brought to a pH of 3.5 in 15 min. With most duodenal ulcer patients,
approximately 50 meq/hr of available antacid is required for neutralization of
gastric contents. Therefore the dosage required depends on the ANC of specific
antacid.
48
PROCEDURE
Preparation of vehicle and suspension
Formula
FORMULA
OFFICIAL FORMULA
WORKING FORMULA
Mg(OH)2
10%w/v
5g
Tragacanth
0.1%w/v
0.05g
Water
q.s
Upto 50ml
0.05g tragacanth was weighed accurately, and transferred to a mortar. Small
quantity of water was added and it was triturated to give a smooth paste. To this
5g of Mg(OH) 2 was added and triturated after adding a required quantity of water.
The suspension so prepared was transferred to the measuring cylinder and the
volume was made up to 50ml. with water after adding all the washings from the
mortar. Suspension adjuvants which are commonly employed in the formulation
are preservative, color, flavor, etc. apart from viscosity imparters. It is always
important to consider possible incompatibilities between the adjuvant before
formulation. The common suspending agents used in the suspension formulations
are modified cellulose polymers, proteins, like gelatin and totally synthetic
polymers.
The modified cellulose polymers used are NaCMC, MC, HPMC, etc. These
polymeric agents function primarily as protective colloids and the viscosity of the
medium. Clays like hydrated aluminium or magnesium silicates can also be used.
Suspensions are evaluated for the following parameters
1. Sedimentation volume
2. Rheological properties
3. Electrokinetic properties
4. Particle size
49
The antacid suspension formulation consist of an antacid compound like
aluminium hydroxide or magnesium (hydroxide) sulphate or calcium carbonate
along with potassium or sodium citrate which prevent thickening of aluminium
hydroxide.
Determination of ANC
The formulation was shaken until the contents were uniform. An accurately
weighed quantity of uniform mixture equivalent to the minimum labeled dosage
(5ml) was transferred to a 250ml beaker and water was added to make up the
volume to about 70ml and it was mixed by using magnetic stirrer at speed of 300
rpm. 30ml of 1N HCl was pipetted into test preparation vehicle and stir with
magnetic stirrer. It was stirred for 15min and after this addition of acid , titration
of this solution was began immediately and in a period not to exceed an addition
of 5min. the excess HCl was titrated with 0.5N NaOH to attain a stable (for 1015s) pH of 3.5. The number of mEq of acid consumed were calculated using the
formula given
Measurement of Viscosity Using Brookfield Viscometer
The viscosity (centipoise) of the sample was determined at 250C using
Brookfield Synchro-electric viscometer; model LVF (Brookfield Laboratories,
Massachusetts) at 100 RPM (spindle #4). All determinations were made in at
least triplicate and the results obtained are expressed as the mean values.
Viscosity of suspending agent h1 = h2 X (N1t1 / N2t2)
Determination of Sedimentation Volume
Each suspension (50 ml) was stored in a 50 ml measuring cylinder for 4 days at
350C. Observations were made every 24 hr for 4 days. The sedimentation
volume, F (%), was then calculated using the following equation.
F = 100 Vu/Vo
50
REPORT
Antacid suspension of magnesium hydroxide was prepared and its acid
neutralizing capacity was found to be
Sedimentation volume
REFERENCES
1. Physical pharmacy, A, Martin, J. Swarbrick, A.C. Ammarata, 3rd edition
2. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems, 8th
edition
3. Essentials of Medical Pharmacology, KD Tripathy, 5th edition
51
EXP.NO:13
DATE:
FORMULATION AND EVALUATION OF GELATIN MICROSPHERES
OF DICLOFENAC SODIUM
AIM
To formulate and evaluate microspheres of diclofenac sodium using bovine
serum albumin.
OBJECTIVE
To develop the modified release dosage form and to study their release
characteristics
MATERIALS REQUIRED
APPARATUS: beaker, magnetic stirrer, standard flask, dissolution apparatus
CHEMICALS: 6.8 pH phosphate buffer, bovine serum albumin, diclofenac
sodium, glutaraldehyde, liquid paraffin
THEORY
Diclofenac sodium is one of the drugs of choice to treat arthritis because
of its potential anti- inflammatory and analgesic activity and this is the only
approved NSAID available for parenteral delivery. Because of shorter biological
half-life, diclofenac sodium should be given frequently to maintain its therapeutic
activity.
It also has high percentage of protein binding and it undergoes presystemic
metabolism. To overcome these problems, many authors developed sustained
release formulations with an intention to maintain effective diclofenac
concentration for prolonged period. Microspheres are sometimes reffered to as
microparticles. Microspheres can be manufactured from various natural and
52
synthetic materials. Polymer used in this experiment is albumin. Albumin is a
natural polymers obtained from sources like proteins.
Methods
1. Single emulsion technique
2. Double emulsion technique
3. Polymerization
4. Phase separation/ Coacervation Spray drying
5. Solvent extraction
6. Emulsion solvent evaporation
7. Wet emulsion technique
8. Hot melt microencapsulation
These are the methods used for the preparation for microspheres.
TYPES OF MICROSPHERES
Bioadhesive microspheres
Adhesion can be defined as sticking of drug to the membrane by using the
sticking property of the water soluble polymers. Adhesion of drug delivery
device to the mucosal membrane such as buccal, ocular, rectal, nasal etc can be
termed as bio adhesion. These kinds of microspheres exhibit a prolonged
residence time at the site of application and causes intimate contact with the
absorption site and produces better therapeutic action.
Magnetic microspheres
This kind of delivery system is very much important which localises the
drug to the disease site. In this larger amount of freely circulating drug can be
replaced by smaller amount of magnetically targeted drug. Magnetic carriers
receive magnetic responses to a magnetic field from incorporated materials that
are used for magnetic microspheres are chitosan, dextran etc.
The different type are
53
Therapeutic magnetic microspheres:
They are used to deliver chemotherapeutic agent to liver tumour. Drugs
like proteins and peptides can also be targeted through this system.
Diagnostic microspheres:
Can be used for imaging liver metastases and also can be used to
distinguish bowel loops from other abdominal structures by forming nano size
particles supramagnetic iron oxides.
Floating microspheres
In floating types the bulk density is less than the gastric fluid and so
remains buoyant in stomach without affecting gastric emptying rate. The drug is
released slowly at the desired rate, if the system is floating on gasteric contentand
increases gastric residence and increases fluctuation in plasma
concentration. Moreover it also reduces chances of striking and dose dumping.
One another way it produces prolonged therapeutic effect and therefore
reduces dosing frequencies. Drug (ketoprofen) given through this form.
Radioactive microspheres
Radio emobilisation therapy microspheres sized 10-30 nm are of larger
than capillaries and gets tapped in first capillary bed when they come across. They
are injected to the arteries that lead to tumour of interest. So all these conditions
radioactive microspheres deliver high radiation dose to the targeted areas without
damaging the normal surrounding tissues.
APPLICATION OF MICROSPHERES
Medical application
 Release of proteins, hormones and peptides over extended period of time.
 Gene therapy with DNA plasmids and also delivery of insulin.
 Vaccine delivery for treatment of diseases like hepatitis, influenza,
pertussis, ricin toxoid, diphtheria, birth control.
54
 Passive targeting of leaky tumour vessels, active targeting of tumour cells,
antigens, by intraarterial/ intravenous application.
 Tumour targeting with doxorubicin and also treatments of leishmaniasis.
 Magnetic microspheres can be used for stem cell extraction and bone
marrow purging.
 Used in isolation of antibodies, cell separation, and toxin extraction by
affinity chromatography.
 Used for various diagnostic tests for infectious diseases like bacterial, viral,
and fungal.
Radioactive microsphere’s application
 Can be used for radioembolisation of liver and spleen tumours.
 Used for radiosynvectomy of arthiritis joint, local radiotherapy,
interactivity treatement.
 Imaging of liver, spleen, bone marrow, lung etc and even imaging of
thrombus in deep vein thrombosis can be done.
Other applications
 Fluorescent microspheres can be used for membrane based technologies
for flow cytomettry, cell biology, microbiology, Fluorescent Linked
Immuno-Sorbent Assay.
 Yttrium 90 can be used for primary treatment of hepatocellular carcinoma
and also used for pretransplant management of HCC with promising
results.
PROCEDURE
Microspheres were prepared by emulsion-coacervation technique, which
contains an aqueous and oily phase.1gm of gelatin was weighed and dissolved in
10ml of distilled water.100mg of drug was dispersed to the above solution. This
55
mixture was heated to 50℃ (care to be taken to prevent overheating).15ml of
liquid paraffin was heated to 50℃ and stirred at 500rpm. To this added 1ml of
tween 20 and stirred to obtain a uniform mixture.
The prepared drug-polymer phase was added drop wise to the oily phase,
which was continuously stirred at 500rpm. The stirring was continued for 5min
for uniform distribution of drug polymer solution. The temperature of the above
solution was lowered to 10ºC and the stirring was continued for 2 hours. After
the first hour, 1.5ml glutaraldehyde was added and stirring was continued for
another 1 hour. The mixture is tightly closed and kept at a temperature for 4ºC
for 24 hours, after which the mixture washed with ice-cold isopropyl alcohol
several times and dried finally.
EVALUATION
Dissolution Study
100mg of prepared loaded microspheres were weighed and placed in dissolution
apparatus. 900ml of 6.8Ph phosphate buffer was used as dissolution medium. The
dissolution study was performed at 50 rpm for 6 hrs. 5 ml of samples were
withdrawn at time interval of 2 hr, 4hr,6hr and after each withdrawal an
equivalent amount of fresh dissolution medium was replaced. Temperature was
maintained at 370c .The absorbance of withdrawn sample after filtration was
measured at 276nm using UVspectrometer. The result were plotted in graph.
Determination of Drug Content
100mg of drug loaded microsperes were added to 100ml of 6.8pH phosphate
buffer.Stirr the dispersion using magnetic stirrer for 3hrs.Filterthe dispersion
using whatmann filter paper and dilute it according to need(take 1ml dilute to
100ml) and measure the absorbance at 276nm.
Percentage Drug Entrapment (%De)
Accurately weighed 100mg of microsphere were dissolved in 100ml PBS
pH 6.8. The solution was kept overnight and was filtered through whatman filter
56
0.45µm. The drug concentration was determined by UV spectrometer at
maximum wavelength of 276nm. The following equation was used to calculate
% drug entrapment:
% Drug Entrapment =
practical drug content
theoretical drug content
× 100
REPORT
 The formulation and evaluation of gelatin microspheres of diclofenac
sodium was prepared.
 The percentage drug release of diclofenac sodium microspheres was found
to be
REFERENCES
1. Eastern pharmacist, July 2000
2. Leon Lachman, Liebermann.H.A.Kaning JL, Theory and practice of
industrial pharmacy,3rd edition,420-428
57
EXP.NO:14
DATE:
FORMULATION AND EVALUATION OF CALCIUM ALGINATE
BEADS OF PARACETAMOL
AIM
To formulate and evaluate the calcium alginate beads of diclofenac
sodium.
OBJECTIVE
To develop the extended release dosage form of diclofenac sodium.
MATERIALS REQUIRED
APPARATUS: beaker, magnetic stirrer, standard flask, dissolution apparatus
CHEMICALS: 6.8 pH phosphate buffer, sodium alginate, paracetamol, 2%
solution of calcium chloride, glutaraldehyde.
THEORY
The United States Pharmacopoeia (USP) defines the modified-release
(MR) dosage form as “the one for which the drug release characteristics of time
course and/or location are chosen to accomplish therapeutic or convenience
objectives not offered by conventional dosage forms such as solutions, ointments,
or promptly dissolving dosage forms”. One class of MR dosage form is an
extended-release (ER) dosage form and is defined as the one that allows at least
a 2-fold reduction in dosing frequency or significant increase in patient
compliance or therapeutic performance when compared with that presented
58
As a conventional dosage form (a solution or a prompt drug-releasing dosage
form). The terms “controlled release (CR)”, “prolonged release”,“sustained or
slow release (SR)” and “long-acting (LA)” have been used synonymously with
“extended release”. Nearly all of the currently marketed monolithic oral ER
dosage forms fall into one of the following two technologies:
1. Hydrophilic, hydrophobic or inert matrix systems: These consist of a rate
controlling polymer matrix through which the drug is dissolved or dispersed.
2. Reservoir (coated) systems where drug containing core is enclosed within a
polymer coating. Depending on the polymer used, two types of reservoir systems
are considered.
(a) Simple diffusion/erosion systems where a drug-containing core is enclosed
within hydrophilic and/or water-insoluble polymer coatings. Drug release is
achieved by diffusion of the drug through the coating or after the erosion of the
polymer coating.
(b) Osmotic systems where the drug core is contained within a semi-permeable
polymer membrane with a mechanical/laser drilled hole for drug delivery. Drug
release is achieved by osmotic pressure generated within the tablet core.
CLINICAL ADVANTAGES:
 Reduction in frequency of drug administration
 Improved patient compliance
 Reduction in drug level fluctuation in blood
 Reduction in total drug usage when compared with conventional therapy
 Reduction in drug accumulation with chronic therapy
 Reduction in drug toxicity (local/systemic)
 Stabilization of medical condition (because of more uniform drug levels)
 Improvement in bioavailability of some drugs because of spatial control
 Economical to the health care provider and the patient
59
LIMITATIONS:
 Delay in onset of drug action
 Possibility of dose dumping in the case of a poor formulation strategy
 Increased potential for first pass metabolism
 Greater dependence on GI residence time of dosage form
 Possibility of less accurate dose adjustment in some cases
 Cost per unit dose is higher when compared with conventional doses
 Not all drugs are suitable for formulating into ER dosage form
Small beads are prepared from different polymers and other
pharmaceutical additives like microcrystalline cellulose and they are used carriers
for development oral sustained release capsules. These beads are filled into the
capsules and they are termed as spansules. The release rate of drugs from these
beads can be altered fast or slow release by coating with various amounts of
polymers. The time of release of drugs from the beads can be modified by
adjusting the thickness of polymer coat. Finally the beads coated with different
thickness and also mixed in different ratios can be put into capsules subsequently
used as modified release capsules.
PROCEDURE
Accurately weighed 500mg of sodium alginate and 25ml of distilled water
was added. These mixture was stirred by using a mechanical stirrer. To this
solution 500mg of paracetamol was added and it is mixed well. By using a syringe
these solution was slowly added into a beaker containing 2% solution of calcium
chloride which is kept under continuous agitation at a low speed using a magnetic
stirrer and stirred for 15 mins. The beads are rigidised by adding 1ml of 25%
solution of glutaraldehyde. Allow the stirring for another 1hr. the solution was
filtered and beads were collected.
60
EVALUATION
Determination of drug content:
100 mg of beads was transferred into 100ml of phosphate buffer 6.8 pH.
The dispersion was stirred using a magnetic stirrer for 2 hrs. The solution was
filtered and diluted with suitable solution. Then the absorbance was measured at
275nm. The drug content of the prepared beads were determined.
Percentage Drug Entrapment (%DE)
Accurately weighed 100mg of microsphere were dissolved in 100ml PBS
pH 6.8. The solution was kept overnight and was filtered through whatman filter
0.45µm. The drug concentration was determined by UV spectrometer at
maximum wavelength of 276nm. The following equation was used to calculate
% drug entrapment:
% Drug Entrapment =
practical drug content
theoretical drug content
× 100
Determination of Swelling Index
500mg of beads was taken in a China dish and then 10 ml ofdistilled water was
added and the mixture was shaken and allowed to stand for 1hour. After 1 hour
the remaining water in China dish was discarded and the weight increase of the
natural suspending agent was rated.
Swelling Index % (SI) = (W2 – W1/W1) x 100
W1= Weight of tablet at time ‘0’
W2= Weight of tablet at time‘t’
Dissolution Test
100mg of prepared drug loaded beads was weighed and placed in
dissolution apparatus. 900ml of pH 6.8 phosphate buffer was used as dissolution
61
medium. The dissolution study was performed at 50 rpm for 3 hr. 5ml of samples
were withdrawn at time interval of 15,30,45,60,and 1 hr and 2hr. After each
withdrawl an equivalent amount of fresh dissolution medium was replaced.
Temperature was maintained at 37ᵒC. the absorbance of withdrawn sample after
filtration was measured at 275nm using UV spectrophotometer. The results were
plotted in a graph.
REPORT
The formulation and evaluation of calcium alginate beads of diclofenac sodium
was performed.
The percentage drug release of diclofenac sodium beads was found to be
REFERENCES
1. Leon Lachmann, Liebermann.H.A.Kaning JL, Theory and practice of
industrial pharmacy,3rd edition,420-428
2. S.P.Vyas, R.K.Khar, “Targeted and Controlled drug delivery”, novel
carrier system, CBS publishers and distributors, New Delhi, page no:
122
62
EXP.NO:15
DATE:
MICROBIAL ASSAY OF GENTAMICIN BY DISC DIFFUSION
METHOD
AIM AND OBJECTIVES
To carry out the microbial assay of gentamicin and determine the antibiotic
presence in given unknown solution by disc diffusion method (Kirby bauer
method)
MATERIALS REQUIRED
APPARATUS: Petriplates, filter paper disc.
CHEMICALS: Gentamicin, agar
THEORY
A standardized filter paper disc agar diffusion procedure known as Kirby bauer
method is frequently used to determine the drug susceptibility of microorganism.
Solutions of known concentrations of antibiotic preparation and the test
preparation are prepared in suitable buffer solution and applied to the disc placed
in the agar medium. Then the petriplates are incubated. After incubation the plates
are examined for the presence of growth inhibition, which is indicated by clear
zone surrounding each disc. The susceptibility on organism to a drug is
determined by the size of this zone which depend on
 Rate of diffusion of the antibiotic into medium and its interaction with the
test organism
 Number of organism incubated
63
 Growth rate of the organism
 Degree of susceptibility of the organism to the antibiotic.
PROCEDURE
Stock solution of gentamicin was diluted in order to obtain graded
concentration of 250, 500, 750, 1000, and 1250µg/ml. aseptically transfer 20µl
of each dilution to the sterile dish which are kept in a sterile petridish (saturated
disc were prepared). Keep it for few minutes. Muller hinton agar was prepared
and sterilized at 121ᵒC for 15 minutes and the media was maintained at room
temperature in order to cool and inoculated with 24hr broth culture of E.coli.
when it attains ear bearing temperature discs with graded concentration of
gentamicin was kept over the surface of solidified agar with sterile forceps and
the plates were incubated at 37oC for 24 hrs. The resultant zone of inhibition of
each standard disc as well as unknown discs were measured and calculate amount
of antibiotic present in the given unknown sample.
REPORT
Assay of gentamicin was done by disc diffusion method and the unknown
concentration of antibiotics from the given sample was found to be
REFERENCES
1. Pharmaceutical microbiology by N.K.Jain.
2. Textbook of microbiology by Ananda Narayanan.
EXP.NO:16
64
DATE:
EVALUATION OF DISINFECTANT BY AGAR PLATE- SENSITIVITY
METHOD
AIM
To evaluate the effectiveness of antiseptic against test organism.
OBJECTIVE
To evaluate the quality of the given disinfectant using agar palte
MATERIALS REQUIRED
Culture: 24-48 hrs. Tryptitase soil broth culture of E.coli
Media: nutrient agar medium / tryptitase soil agar
Disinfectant: isopropyl alcohol (70% IPA), hydrogen peroxide (3%), tincture of
iodine and phenol.
Equipment: sterile disc, forceps, cotton swab, Bunsen burner, glass marking
pencil and routine microbiological facilities.
THEORY
This procedure require the heavy inoculation of an agar plate with the test
organism. Sterile, colour coded filter paper disc are impregnated with a different
antiseptic and equally spaced on the inoculated agar plate. Following incubation
the agar plate is examined for zone of inhibition (area of no bacterial growth)
surrounding the disc. A zone of inhibition is indicative of microbial activity
against the organism. Absence of a zone of inhibition indicate the chemical was
ineffective against the test organism.
The size of the zone of inhibition is not indicative of the degree of
effectiveness of the chemical agent.
65
PROCEDURE
Preparation of medium
Nutrient agar was prepared and sterilized at 121OC for 15 minutes. Then
was poured into a sterile petri dishes and allowed to stand for solidification. A
lawn culture was made on solidified agar and the plate was partitioned into 5
portions and labelled with respective disinfectants.
Preparation of disc
The disinfectant were prepared and the sterile disc was dipped into
disinfectant inorder to obtain saturated discs.
The discs were prepared, placed over the surface of lawn culture at the
respective portion and incubated at the respective portion and incubated at 37oC
for 24-48hrs. After the incubation observed the plates for the zone of incubation.
Observed the plates for the zone of inhibition surrounded each of the impregnated
discs and control. Based on data obtained reported those disinfectants develops
zone of inhibition.
REPORT
Evaluation of disinfectants by agar plate sensitivity method was done and it was
found that the phenol is showing maximum disinfectant activity. Effectiveness of
disinfectants was found to be in the order of phenol > hydrogen peroxide> iodine>
isopropyl alcohol.
REFERENCES
1. Pharmaceutical microbiology by N.K.Jain.
2. Textbook of microbiology by Ananda Narayanan
66
EXP.NO: 17
DATE:
VALIDATION OF STERILIZATION
AIM
To prepare a validation protocol for steam sterilization (autoclave)
validation of steam sterilization.
THEORY
This protocol provides a standard procedure for the validation of steam
sterilization autoclave.
Items that are to be sterilized but which cannot withstand the high
temperature of the dry heat are sterilized by steam in autoclave at temperature of
121oC.
Responsibility
The validation group is responsible for overall adherence to this protocol.
Their specific duties include the following.
1. Maintaining of protocol completeness, accuracy, technical excellence and
applicability
2. Maintenance and calibration of validation equipment
3. Scheduling of the validation runs
4. Conducting the validation runs including recording of all data
5. Data review and validation run acceptance
6. Validation report preparation
7. Schedule any necessary validation
67
Validation test programme
The following studies should be completed as a part of the validation programme
1. Heat distribution studies with empty and loaded autoclave
2. Heat penetration studies in a loaded autoclave
Empty chamber heat distribution study
Three runs will be performed to qualify the measurement of the temperature
throughout the chamber by atleast 10 or 12 point thermocouples during a
minimum of 30 cycles.
The heat distribution test should be performed to ascertain whether the
temperature at different location in the chamber is nearly uniform throughout the
cycles.
Loaded chambers heat distribution
 Three runs of three representative configuration shall be performed
 Loading pattern: an exact load configuration must be established. This
includes the number of wrapping materials, containers and others along
with their sizes such that the load can be standardized
 Load the autoclave with normal sterilization load. Load 12 probes of the
temperature indicators at various places around the load with one being in
the steam drain. Note the location of each probe and mark in the diagram
showing the load and location probes with validation report.
 Probe should be outside the articles and not inside. Release steam in the
chamber and note startup time and temperature of digital thermometer.
Heat penetration study
Three runs of each representative configuration shall be performed for heat
penetration test
68
The same loading pattern as in heat distribution test is to be used. The validation
must be performed under normal operating condition. E.g. wrapped and washed
items should be treated using normal process and usual conditions. Place atleast
ten thermocouples inside the product or equipment that is loaded into the
chamber. One thermocouple must be placed in the cold spot which was
determined from previous heat distribution studies of the same standard load time
with the article being sterilized is located in this area and thermocouple must be
inside it.
Each item must have atleast one thermocouple placed in its most inaccessible
location. One thermocouple must be placed in the cold spot. Keep one probe near
the steam drain.
Release the steam into the chamber and note start up time and temperature of
digital thermometer. Continue recording time.
Digital thermometer temperature and temperature of each probe every time
Evaluation of results
The heat penetration information will be used to establish run reproducibility. If
the analysis of the accumulated data demonstrate a consistent, uniformly and
lethal process(reproducible over three runs) the load configuration and other
parameters are satisfactory.
The data obtained in the course of study will be used to define sterilization process
parameters for each load configuration and will include the following information
a minimum.
1. A minimum of equivalent to 5, 15 minutes including the probe in the
coolest location
2. A definite loading configuration including identification of all wrapping
materials
69
Final validation report
A report will be issued describing the validation qualification programme,
including the result of each phase of study conducted, and the validated process
parameters and load configuration. The report will be prepared by the validation
group.
70
EXP.NO:18
DATE:
PROTOCOL FOR AMOXYCILLIN ORAL SUSPENSION
AIM
To prepare protocol for amoxicillin oral suspension.
LABELLED FORMULA
Each ml of reconstituted suspension contains
Amoxicillin trihydrate equivalent to amoxicillin-125mg
Batch size: 3000
Usual packing: 20gm in 70 ml capacity glass bottle with mark of 40ml.
FORMULATION
Sl.No
Ingredients
Quantity for 3000 Bottles(kg)
1
Amoxicillin trihydrate
3.8
2
Carboxymethylcellulose
1.1
3
Aerosil
0.450
4
Color (tartazine)
0.012
5
Sodium benzoate
0.270
6
Sugar (pharma grade)
7
Pineapple flavor
54
0.600
71
MANUFACTURING SPECIFICATION AND PROCESS
1. Mix all the ingredients under controlled condition of temperature and
moisture for 30 minutes.
2. Use the entire ingredients after sifting through stainless steel sieve.
3. Fill 20gm in each bottle and close immediately
72
EXP.NO:19
DATE:
PROTOCOL FOR GENTAMICIN INJECTION
AIM
To prepare protocol for gentamicin injection
FORMULA
Ingredients
Quantity/ampoule(g)
Quantity for 10 litre
Gentamicin sulphate
0.06
150
Methyl paraben sodium
0.6
4
Propyl paraben sodium
0.06
0.4
Sodium metabisulphate
3
20
Disodium edetate
0.3
2
Dilute sulphuric acid
QS
10
(11ml) in water for inj.
Reason to add above ingredients in this preparation
1. Methyl paraben and propyl paraben are used as antimicrobial
preservatives.
2. Sodium metabisulphate is used as antioxidant in this preparation
3. Disodium edetate is used as a chelating agent, binds the heavy metal if
present in the preparation.
73
4. Dilute sulphuric acid is used to maintain the pH of the preparation.
5. Water for injection is used as carrier(vehicle)
METHOD
STEP 1: Preparation of Water for Injection
Water for injection is prepared by triple distillation in a still specially
designed to produce the high quality water required. Vapour compression stills
are mainly used.
STEP 2: Storage and Distillation
Stored in a closed container (stainless steel) at about 80oC. distributed
through stainless steel pipelines.
STEP 3: Cleaning Equipment and Containers
Scrubbed by hand immediately after previous use with detergent
(particular) to screw thread, joints etc.) Live steam can be used to loosen the
debris. Rinsed several times with water for injection. Rinsed just before use with
water for injection. They should be removed in front of HEPA- laminar flow unit.
STEP 4: Sterilization of Equipment
Should be done after cleaning but prior to use. Done by moist heat(gaseous
sterilization is also used).
STEP 5: Compounding of Product
Done under aseptic conditions. Water for injection is de-aerated by passing
nitrogen gas through it for 15min. to this methyl paraben sodium, propyl paraben
sodium, sodium metabisulphite by moist heat (gaseous sterilization is also used),
disodium edetate are added and dissolved to get clear solution. Proper mixing is
done using propeller. To this 11ml of dilute sulphuric acid is added and pH is
checked. Filtered through hyflosupercel media pad followed by G-3 sintered glass
74
funnel and pass nitrogen gas for another 30 min. dissolve gentamicin sulphate to
get a clear solution. Check the pH and adjust to pH 4.
STEP 6: Filtration of the Solution
Filtered through G-3 sintered glass funnel and finally through 0.22µ
membrane filter.
STEP 7: Filling of the Liquids
Gravimetric filling is done. Slight excess (0.01%) is added as overage.
STEP 8: Sealing of Ampoules
Done in aseptic area. The ampoules were sealed by using flame by tip seal
method.
STEP 9: Sterilization of The Product
The product is sterilized by autoclaving (100oC for 30 min)
STEP 10: Quality Control
Leaker test
A vaccum of about 27 inches Hg is applied within the ampoules and
immersed in methylene blue (0.5-1%) dye. The dye is entered via the opening or
not is seen after proper washing of ampoule from outside.
Clarity test
The individual particle were tested and discarded if any particles are found
in them. Individual containers are visualized against light and dark background.
Content is made swirling to ease the identification of the particulate matter
Pyrogen test
LAL test: the content is incubated with limulus polyphemus at 37oC for 60
min. if pyrogens are present, the sample forms gel.
75
STEP 11: Packaging
1. Label and identify label
2. Should protect it from damage during transport, handling and storage.
76
EXP.NO:20
DATE:
PROTOCOL FOR MULTIVITAMIN TABLETS
AIM
To prepare protocol for multivitamin tablets
Brand name: Neurobion forte
Size of tablet: 250 mg.
FORMULA
Ingredients
Quantity for 1 tablet
Quantity for 10000
(mg)
tablets(g)
Thiamine mono nitrate
10
100
Riboflavin
10
100
Pyridoxine HCl
3
30
Cyanocobalamine
15
150
Niacinamide
45
450
Calcium pantothanate
50
500
Lactose
75
750
Starch
21.3
213
Talc
20
200
Stearic acid
0.7
7
Weight of granulation
250
2500
77
Reasons for inclusion of ingredients
Vitamin
: as prophylactic
Lactose IP
: diluents
Starch IP
: disintegrant
Talc
: glidant
Stearic acid
: lubricant
METHOD
Stage 1: Sieving
Sieve all material using mesh no:80/100
Stage 2: Weighing
Stage 3: Dry blending
All weighed materials are blended in planetary mixer (7-10 HP, 100200Kg materials)
Stage 4: Dry granulation(slugging)
Dry granulation is mixed ingredients is done using Chilosator (Fitz-Patric
Company) with pressure 10-15 tones/leniar inch. Capacity 500kg/hr.
Stage 5: Screening
Screen for 14-16 mesh size
Stage 6: Slugging
Continue slugging process till granules follows normal particle distribution
curves.
Stage 7: Compression
Compress the granules into tablets using a ¼ inch concave punch or colton
rotary tablet press. Number of stations available, minimum-12, maximum-90.
78
IN PROCESS CONTROL PARAMETERS
Physicochemical properties of ingredients, the order of addition of
compounds to the blender, mixing speed, mixing time, use of auxiliary dispersion
equipment within the mixer, mixing action, blender load, slugging, and
compression force.
Packaging: strip/blister packing/ glass container.
Storage: stored in tightly closed, light resistant container.
Quality control tests
 Uniformity of a container contents(glass container)
 Content of active ingredients IP
 Uniformity of weight IP
 Uniformity of contents IP
 Disintegration test IP
 Dissolution test IP
Non official tests
 Hardness and friability
 Stability studies according to ICH guidelines
79
EXP.NO:21
DATE:
PROTOCOL FOR BETAMETHASONE AND NEOMYCIN SKIN
OINTMENT
AIM
To prepare skin ointment of betamethasone and Neomycin.
LABELLED FORMULA
Betamethasone valerate 0.12% w/w, neomycin sulphate 0.5%w/w
FORMULATION
Sl.no
Ingredients
Quantity (for 1kg)(g)
1
Betamethasone valerate
18.50
2
Neomycin sulphate
80.00
3
Cetosteryl alcohol
1.0
4
Cetomacrogol 1000
750.00
5
White soft paraffin
11.25
6
Liquid paraffin
1.50
MANUFACTURING SPECIFICATIONS
1. Use 3.5 g aluminium collapsible tubes
2. Pass nitrogen gas through melted waxes to improve stability
3. Antioxidants like propyl gallate or sodium metasulphate may be
incorporated in the formulation to protect the deterioration of neomycin
sulphate.
80
4. Heat cetosteryl alcohol, cetomacrogol 1000 and white soft paraffin to
100oC and filter through cloth
5. Allow the melted waxes to cool to room temperature.
6. Triturate betamethasone valerate and neomycin sulphate with half of liquid
paraffin to form smooth paste.
7. Add the above two mixtures with stirring at a temperature not exceeding
40oC.
8. Pass the ointment through triple roller mill to minimize particle size.
9. Fill the ointment in aluminium collapsible tube.
10. Send a sample to QC for evaluation.
81
EXP.NO:22
DATE
PROTOCOL FOR MAGALDRATE AND SIMETHICONE SUSPENSION
AIM
To prepare protocol for Magaldrate and Simethicone suspension
CATEGORY
Antacids
LABELLED FORMULA
Each 5ml contains : Magaldrate- 400mg
Simethicone – 60mg
FORMULATION
Sl.no
Ingredients
Quantity for 750 Litre(kg)
1
Magaldrate
75
2
Activated Simethicone
9.00
3
CMC Sodium
8.00
4
Sodium benzoate
3.80
5
Methyl paraben sodium
1.10
6
Propyl paraben sodium
10.00
7
Tween 80
3.30
8
Sorbitol
50.00
9
Glycerin
25.00
10
Citric acid
400g
82
11
Flavor
2.00ml
12
Demineralized water
QS
MANUFACTURING SPECIFICATIONS
1. Use 180ml white glass bottle with 28mm pp. cap
2. pH range 8.0-9.0
3. Stirring should be continued during filling
MANUFACTURING PROCESS
1. To 200 litre DM water in a tank, suspend 8kg CMC sodium slowly with
constant stirring.
2. Dissolve sodium benzoate, methyl paraben and propyl paraben sodium in
10 litre DM water and added to the above solution.
3. Keep overnight, pass the jelly through colloid mill and transfer to the
mixing tank fitted with stirrer.
4. Add sorbitol to the above mixture.
5. Mix glycerin with tween 80 and activated simethicone. Mix for 30 minutes
and add to the above mixture.
6. Dissolve citric acid in 10 litre DM water and add to the bulk.
7. Slowly and magaldrate to the bulk under constant stirring.
8. Add the flavor and make up the volume to 750 litres with water.
9. Mix thoroughly for 4 hrs. Keep it overnight.
10. Make up the volume once again. Mix and pass the suspension through
colloid mill.
11. Fill into 180ml in white glass bottle.
83
EXP.NO:23
DATE:
PROTOCOL FOR SUSTAINED RELEASE MATRIX TABLET OF
DICLOFENAC POTASSIUM
AIM
To prepare the protocol for sustained release matrix tablet of diclofenac
potassium.
CATEGORY
NSAIDs
FORMULATION
Sl.no
Ingredients
Quantity for 1tablet(mg) Quantity
tablets(g)
1
Diclofenac
100
100
potassium
2
HPMC
40
40
3
Microcrystalline
60
60
10
10
2%
2%
2%
2%
cellulose
4
Polyvinyl
pyrrollidone
5
Magnesium
stearate
6
Talc(purified)
84
for
1000
PROCEDURE
Weigh the required quantity of diclofenac potassium and mix it with HPMC and
microcrystalline cellulose.
Prepare the granules using 20% polyvinyl pyrrollidone in isopropyl alcohol.
Pass the dried granules through sieve no.16 and dried at 40oC for 45minutes.
Lubricate the granules with the suitable lubricant and glidant and compress in a
single punch machine.
85
CALIBRATION CURVES
86
PREPARATION OF CALIBRATION CURVE FOR DICLOFENAC
SODIUM
Prepared a stock solution (1mg/ml) of pure drug Diclofenac sodium by
dissolving 100mg of drug in 100ml phosphate buffer6.8pH. prepared various
working standards namely 5µg/ml, 10µg/ml, 15µg/ml, 20µg/ml and 25µg/ml by
appropriate dilution from the stock solution. Measured the absorbance of these
solutions at λmax of 276nm and developed a calibration curve by plotting
concentration on x axis against the absorbance in y axis. Determined the slope
from the calibration curve.
87
PREPARATION OF CALIBRATION CURVE FOR PARACETAMOL
Prepared a stock solution (1mg/ml) of pure drug Diclofenac sodium by
dissolving 100mg of drug in 100ml phosphate buffer 6.8pH. Prepared various
working standards namely 2µg/ml, 4µg/ml, 6µg/ml, 8µg/ml and 10µg/ml by
appropriate dilution from the stock solution. Measured the absorbance of these
solutions at λmax of 257nm and developed a calibration curve by plotting
concentration on x axis against the absorbance in y axis. Determined the slope
from the calibration curve.
88
PREPARATION OF CALIBRATION CURVE FOR DICLOFENAC
POTASSIUM
Prepared a stock solution (1mg/ml) of pure drug Diclofenac sodium by
dissolving 100mg of drug in 100ml phosphate buffer6.8pH. Prepared various
working standards namely 1µg/ml, 2µg/ml, 3µg/ml, 4µg/ml and 5µg/ml by
appropriate dilution from the stock solution. Measured the absorbance of these
solutions at λmax of 275nm and developed a calibration curve by plotting
concentration on x axis against the absorbance in y axis. Determined the slope
from the calibration curve.
89
APPENDIX
90
EQUATIONS
Drug content
Drug content =
𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 ×𝑣𝑜𝑙.𝑜𝑓.𝑑𝑖𝑠𝑠.𝑚𝑒𝑑𝑖𝑢𝑚×𝑑𝑖𝑙𝑢𝑡𝑖𝑜𝑛 𝑓𝑎𝑐𝑡𝑜𝑟
1000
Drug Loading Efficiency (Dl)
Drug loading capacity (DL) was calculated according to the following equation
DL (%) =
𝑊𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑖𝑛 𝑚𝑖𝑐𝑟𝑜𝑠𝑝ℎ𝑒𝑟𝑒𝑠
𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑚𝑖𝑐𝑟𝑜𝑠𝑝ℎ𝑒𝑟𝑒𝑠
x 100
Percentage drug entrapment (%)
% Drug Entrapment =
practical drug content
theoretical drug content
× 100
Swelling index (%)
Swelling index =
𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑠𝑤𝑜𝑙𝑙𝑒𝑛 𝑚𝑖𝑐𝑟𝑜𝑠𝑝ℎ𝑒𝑟𝑒𝑠−𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑑𝑟𝑖𝑒𝑑 𝑚𝑖𝑐𝑟𝑜𝑠𝑝ℎ𝑒𝑟𝑒𝑠
𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑠𝑤𝑜𝑙𝑙𝑒𝑛 𝑚𝑖𝑐𝑟𝑜𝑠𝑝ℎ𝑒𝑟𝑒𝑠
Percentage drug release (%)
% Drug release =
𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 ×𝑣𝑜𝑙.𝑑𝑖𝑠𝑠.𝑚𝑒𝑑𝑖𝑢𝑚×𝑑𝑖𝑙𝑢𝑡𝑖𝑜𝑛 𝑓𝑎𝑐𝑡𝑜𝑟
𝑠𝑡𝑟𝑒𝑛𝑔𝑡ℎ×1000
x100
Percentage drug diffused (%)
% Drug diffused =
𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 ×𝑣𝑜𝑙.𝑑𝑖𝑠𝑠.𝑚𝑒𝑑𝑖𝑢𝑚×𝑑𝑖𝑙𝑢𝑡𝑖𝑜𝑛 𝑓𝑎𝑐𝑡𝑜𝑟
𝑠𝑡𝑟𝑒𝑛𝑔𝑡ℎ×1000
91
x100
x100
Bulk density
Bulk density =
weight of sample in gm
volume occupied by the sample
Tapped density
Tapped density =
weight of sample in gm
volume occupied by the sample after tapping
Consolidation index
Consolidation index (%) =
𝑇𝑎𝑝𝑝𝑒𝑑 𝑑𝑒𝑛𝑠𝑖𝑡𝑦−𝐵𝑢𝑙𝑘 𝑑𝑒𝑛𝑠𝑖𝑡𝑦
𝑇𝑎𝑝𝑝𝑒𝑑 𝑑𝑒𝑛𝑠𝑖𝑡𝑦
Angle of repose
θ = tan−1 h r
Where,
Ɵ = angle of repose
h = height of the pile
r = Average radius of the powder cone
Porosity (%)
Porosity (%) =
𝑏𝑢𝑙𝑘 𝑣𝑜𝑙𝑢𝑚𝑒−𝑡𝑎𝑝𝑝𝑒𝑑 𝑣𝑜𝑙𝑢𝑚𝑒
𝑏𝑢𝑙𝑘 𝑣𝑜𝑙𝑢𝑚𝑒
Hausner’s ratio
Hausner’s ratio =
𝑇𝑎𝑝𝑝𝑒𝑑 𝑑𝑒𝑛𝑠𝑖𝑡𝑦
𝐵𝑢𝑙𝑘 𝑑𝑒𝑛𝑠𝑖𝑡𝑦
92
x100
x100
Types of Tablet:-
IP
BP
USP
Uncoated
Uncoated
Compressed/molded
Film Coated
Coated
Plain Coated
Enteric Coated
Gastro
Resistant Delayed Release
(Enteric Coated)
Dispersible Tablet
Dispersible Tablet
Dispersible Tablet
Modified Release Tablet Modified Release Tablet Extended
Tablet
Release
Soluble Tablet
Soluble Tablet
Soluble Tablet
Effervescent Tablet
Effervescent Tablet
Effervescent Tablet
For use in mouth For use in mouth Chewable/Buccal,
(Chewable, Lozenges, (Chewable, Lozenges, Sublingual
Sublingual)
Sublingual)
Orodispersible
Orodispersible
Orodispersible
BP
USP
Standards for Tablets:IP
Content
of
Ingredient
Active Content
of
Ingredient
Active Content
of
Ingredient
Active
Uniformity of weight
Uniformity of weight
Weight Variation
Uniformity of Content
Uniformity of Content
Uniformity of Content
DT
DT
DT
Dissolution
Dissolution
Dissolution
93
1) Content of Active Ingredient: - 1) Assay of Active
2) 20 tabs: - Limits 90% to 110%
2) Uniformity of Weight/Wt Variation:20 tabs, calculate avg. wt NMT 2 deviate, none twice the limits
Weight Variation Limits:1) For Tablets
IP/BP
Limit
USP
80 mg or less
10%
130mg or less
More than 80mg 7.5%
or Less than
250mg
130mg to
324mg
250mg or more
More than
324mg
5%
IP
Limit
Less than 300mg
10%
300mg or More
7.5%
2) For capsules
Friability Test: This test is additional to check crushing strength of tablet by
this test one can check Capping &/or Lamination. USP limit is 0.5 to 1%.
Rotation: - 25 rpm or 100 rotations in 4 min.
Uniformity of Content or Content Uniformity:IP: - Active less than 10mg or 10%,
BP:- Active less than 2 mg or 2%,
USP:- Active less than 25mg or 25%.
94
-10 tabs limit NMT 1 tab deviate 85 – 115% & none outside 75 – 125% of the
Avg value/IP/BP/USP (Relative Standard Deviation less than or equal to 6%),
- If 2 or 3 individual values are outside the limits 85 – 115% of the Avg value,
& none outside 75 – 125% repeat for 20 tabs.
- Complies when 30 tabs NMT 3 of the individual values are outside the limit
85 – 115% of the Avg value, and none outside 75 – 125%.
Disintegration Time:Uncoated Tablet
NMT 15 min, in water with Disc 370C ± 20C
Coated Tablet
NMT 30 min, In water with Disc for Film Coated
Tab, and NMT 60 min Other than Film coated tablet
Enteric Coated
Intact for 1 hr in 0.1 N HCl & disintegrate within 2 hr
Tab
in Mixed 6.8 Phosphate buffer. According to USP 1 hr
in Simulated gastric fluid, then in Simulated Intestinal
Fluid.
Dispersible/Soluble Within 3 min in water at 250C ± 10C (IP) & 15 – 250C
(BP)
Orodispersible
Within 1 min
Effervescent Tab
5 min in 250 ml water at 20 – 300C (IP) & 5 min in
200 ml water at 15-250C (BP)
Buccal &
Not Applicable but dissolve within 15 – 30 min.
Sublingual
95
DT Apparatus:- Mesh Apperture:- 2mm (#10), Cycles:- 28 – 32 cycles/min, 50
– 60 mm distance from bottom & top, Temp of water 370C ± 20C. If 1 or 2 tabs
fail, repeat for 12 tabs.
Solubility:BP SOLUBILITIES
Very soluble
less than 1 part
Freely soluble
from 1 to 10 parts
Soluble
from 10 to 30 parts
Sparingly soluble
from 30 to 100 parts
Slightly soluble
from 100 to 1000 parts
Very slightly soluble
from 1000 to 10,000 parts
Practically insoluble
more than 10,000 parts
Approximate quantity of solvent by volume for one part of
soluble by weight. For example, 1g of a very soluble
substance dissolves in less than 1ml of solvent (1gm/ml).
Compressibility Index (Carr’s Index)
Flow
C.I (%)
property
Hausner
ratio
Excellent
≤10
1.00 – 1.11
Good
11 – 15
1.12 – 1.18
96
Fair
16 – 20
1.19 – 1.25
Passable
21 – 25
1.26 – 1.34
Poor
26 – 31
1.35 – 1.45
Very poor
32 – 37
1.46 – 1.59
Very, very
>38
>1.60
poor
Angle of Repose
Flow property
Angle of repose
(degrees)
Excellent
25 – 30
Good
31 – 35
Fair-aid not needed
36 – 40
Passable – may hang
41 – 45
up
Poor – must agitate,
46 – 55
vibrate
Very poor
56 – 65
Very, very poor
>66
Bioavailability:- The rate and extent to which the active ingredient or active
moiety is absorbed from a drug product and becomes available at the site of
97
action. For drug products that are not intended to be absorbed into the
bloodstream, bioavailability may be assessed by measurements intended to
reflect the rate and extent to which the active ingredient or active moiety
becomes available at the site of action.
ANDA - Abbreviated New Drug Application.
IND – Investigational New Drug Application.
NDA – New Drug Application.
According to the BCS, drug substances are classified as follows:
Class I - High Solubility, High Permeability
Class II - High Permeability, Low Solubility
Class III -High Solubility, Low Permeability
Class IV - , Low Solubility Low Permeability

A drug substance is considered HIGHLY SOLUBLE when the highest
dose strength is soluble in < 250 ml water over a pH range of 1 to 7.5.

A drug substance is considered HIGHLY PERMEABLE when the extent
of absorption in humans is determined to be > 90% of an administered
dose, based on mass-balance or in comparison to an intravenous reference
dose.

A drug product is considered to be RAPIDLY DISSOLVING when >
85% of the labeled amount of drug substance dissolves within 30 minutes
using USP apparatus I or II in a volume of < 900 ml buffer solutions.
DISSOLUTION DETERMINATION

USP apparatus I (basket) at 100 rpm or USP apparatus II (paddle) at 50
rpm.
98

Dissolution media (900 ml): 0.1 N HCl or simulated gastric fluid, pH 4.5
buffer, and pH 6.8 buffer or simulated intestinal fluid.

Compare dissolution profiles of test and reference products using a
similarity factor (f2).
AN ARRAY OF TABLET TYPES
Immediate Release Uncoated Tablets: Usually no taste/stability issues.
Coated Tablets: For taste/stability/identification (coated with watersoluble/dispersible polymer–mixture of hydroxypropyl
cellulose/hydroxypropylmethyl cellulose); coating readily ruptures in GI tract.
Enteric-Coated Tablets: For drugs inactivated or destroyed in the stomach or
for those causing irritation to the gastric mucosa; tablet passes through the
stomach but disintegrates in the intestines where absorption takes place.
Excipients used for enteric coating include cellulose acetate phthalate, mixtures
of fats and fatty acids, etc.
Multiple Compressed Tablets: Multiple-layered tablets manufactured by using
more than one compression cycle. Each layer contains a different drug and each
may be colored differently.
Controlled Release Tablets: Improved therapy, less toxicity, improved patient
compliance—using polymers such as methacrylates.
Sublingual Tablets: Small, flat ovals such as nitroglycerin. They are ideal
tablets for absorption of drugs which are destroyed by gastric juice or undergo
first pass metabolism.
99
Chewable Tablets: Disintegrate rapidly when chewed for patients with
swallowing difficulty (children, elderly) and when there is no access to water.
Most commonly used for multiple vitamins and antacids.
Effervescent Tablets: In addition to the active, this product form contains
sodium bicarbonate and citric acid. When water is added the ensuing chemical
reaction forms carbon dioxide, which acts as a disintegrant and produces
effervescence that hastens dissolution (antacids).
Official Standards as per I.P. / B.P. / U.S.P.
COMPARISON OF DIFFERENT PHARMACOPOEIAL QUALITY
CONTROL TESTS
PHARMACOPOEIAS
TYPE OF
TESTS TO BE
TABLET
PERFORMED
Content of active ingredients
For all tablets
Disintegration
Uniformity of content
Labeling
BRITISH
PHARMACOPOEIA
Uncoated tablet
Disintegration test
Uniformity of weight
Effervescent
Disintegration test
tablet
Uniformity of weight
Coated tablet
Disintegration test
Uniformity of weight
100
Gastro resistant
tablet
Modified release
tablet
Tablet for use in
mouth
Soluble tablet
Disintegration test
Uniformity of weight
Uniformity of weight
Disintegration test
Uniformity of weight
Disintegration test
Dispersible
Uniformity of dispersion
tablet
Uniformity of weight
Uniformity of container content
Content of active ingredient
Uncoated tablet Uniformity of weight
Uniformity of content
Disintegration test
INDIAN
PHARMACOPOEIA
Enteric coated
Disintegration test
tablet
Dispersible
Uniformity of dispersion
tablet
Disintegration
Soluble tablet
Disintegration test
101
Disintegration/ Dissolution /
Effervescent
Dispersion
tablet
test
Bulk density /Tapped density of
powder
Powder fineness
Physical tests
UNITED STATES
applicable to
PHARMACOPOEIA
tablet
Loss on drying
Disintegration test
Tablet friability
Dissolution test
formulation
Drug release testing
Uniformity of dosage form
Container permeation test
Labeling of inactive ingredients
102