RECTAL PREPARATIONS
Industrial technology of
the suppositories.
Plan
1. Rectal preparations. Classification of the rectal
preparations.
2. Suppositories. General characteristic of
suppositories.
3. Methods of suppositories production in
industrial.
4. Equipments for suppositories production in
industrial.
5. Standardization of suppositories.
Rectal preparations are intended for
rectal use in order to obtain a
systemic or local effect, or they may
be intended for diagnostic
purposes.
Where applicable, containers for rectal
preparations comply with the requirements
for Materials used for the manufacture of
containers and Containers.
Several categories of rectal
preparations:






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suppositories,
rectal capsules,
rectal solutions, emulsions and suspensions,
powders and tablets for rectal solutions and
suspensions,
semi-solid rectal preparations,
rectal foams,
rectal tampons.
Suppositories – dosage form which
are solid at room temperature and
melting or dissolving at body
temperature are intended for
administration in the body cavity.
Suppositories are solid, single-dose
preparations.
The shape, volume and consistency of
suppositories are suitable for rectal
administration.
Rectal capsules
(shell suppositories)
are solid, single-dose preparations
generally similar to soft capsules as
defined in the monograph on Capsules
except that they may have lubricating
coatings.
They are of elongated shape, are smooth
and have a uniform external appearance.
Rectal solutions, emulsions and suspensions
are liquid preparations intended for rectal use
in order to obtain a systemic or local effect, or
they may be intended for diagnostic purposes.
Rectal solutions, emulsions and suspensions are supplied
in single-dose containers and they contain one or more
active substances dissolved or dispersed in water,
glycerol or macrogols or other suitable solvents.
Emulsions may show evidence of phase separation but are
readily redispersed on shaking.
Suspensions may show a sediment which is readily
dispersible on shaking to give a suspension which
remains sufficiently stable to enable the correct dose to
be delivered.
Powders and tablets intended for the
preparation of rectal solutions or
suspensions are single-dose preparations
which are dissolved or dispersed in water at
the time of administration.
They may contain excipients to facilitate
dissolution or dispersion or to prevent
aggregation of the particles.
After dissolution or suspension, they comply
with the requirements for rectal solutions or
rectal suspensions, as appropriate.
Semi-solid rectal preparations
are ointments, creams or gels.
They are often supplied as single-dose preparations in
containers provided with a suitable applicator.
Semi-solid rectal preparations comply with the
requirements of the monograph on Semi-solid
preparations for cutaneous application.
Semi-solid preparations for cutaneous application are
intended for local or transdermal delivery of active
substances, or for their emollient or protective action.
They are of homogeneous appearance.
Rectal tampons
are solid, single-dose preparations intended
to be inserted into the lower part of the
rectum for a limited time.
Suppositories contain one or more active
substances dispersed or dissolved in a suitable
basis which may be soluble or dispersible in
water or may melt at body temperature.
Excipients such as
 diluents,
 adsorbents,
 surface-active agents,
 lubricants,
 antimicrobial preservatives
 colouring matter
authorised by the competent
authority, may be added if
necessary.
Classification
a.
Rectal suppositories for adults weigh 2 gm
and are torpedo shape. Children's suppositories
weigh about 1 gm.
b.
Vaginal suppositories or Pessaries weigh
about 3-5gm and are moulded in globular or
oviform shape or compressed on a tablet press
into conical shapes.
c.
Urethral suppositories called bogies are
pencil shape. Those intended for males weigh 4
gm each and are 100-150 mm long while those
for females are 2 gm each and 60-75 mm in
length.
Advantages of suppositories:
1. Suppositories are precise dosage forms
containing accurate quantities of
medicament(s).
2. Suppositories have been used for systemic
distribution when the oral administration was
not suitable, as in unconscious patients and
infants. Suppositories simplify or eliminate the
problem of infant medication.
3. Suppositories allow administration of some
medicaments, which are not tolerated orally,
e.g. medicaments which are sensitive to the
gastric pH and gastric enzymes.
Advantages of suppositories:
4. Suppositories permit administration of
medicament that interrupt the functionality of the
gastrointestinal tract e.g. drugs irritating to the
stomach.
5. Suppositories are useful when the stomach is not
the ideal position to receive medication such as in
case of nausea and vomiting.
6. Suppositories are suitable when local effect is
wanted as in the treatment of rectal, vaginal and
urethral diseases.
7. Suppositories have shown faster onset of action
than found after oral administration as the drug is
directly absorbed from the mucosa into the
venous circulation.
Advantages of suppositories:
8. Drugs destroyed by portal
circulation may bypass the liver
circulation, where many drugs
subject to metabolic changes (first
pass effect).
Disadvantages of Suppositories:
1.
The problem of patient acceptability.
2.
Suppositories are not suitable for patients
suffering from diarrhea.
3.
In some cases the total amount of the drug
must be given will be either too irritating or
in greater amount than reasonably can be
placed into suppository.
4.
Incomplete absorption may be obtained
because suppository usually promotes
evacuation of the bowel.
On the speed of absorption of drugs with
suppositories such physiological factors
affect:
1.
State of the rectum.
2.
Circulation of blood suction surface.
3.
Muscle tone and mucus layer on the surface
of the walls of the rectum.
4.
- Nature of the basis is the most influential
factor on the absorption of active
ingredients from suppositories.
Requirements to suppository bases:
1.
They must retain sufficient hardness at room
temperature.
2.
Temperature of melting or dissolution must be
close to the temperature of the human body.
3.
Should not irritate the mucous membrane of the
rectum and cause other undesirable activities
that should be physiologically neutral.
4.
Should not prevent the release and the
therapeutic act of medicinal substances.
5.
Should not interact with drugs, which
administered in the suppository mass.
Technological requirements to
suppository bases:
1. Chemical and physical stability of the base during
manufacture and storage of suppositories;
2. Ability to easily form and maintain the necessary
hardness when you enter;
3. Ability emulsify required number of solutions;
4. Have some plasticity, viscosity, total time of
deformation, that certain structural and mechanical
properties.
Methods of suppositories
production in industrial
1. Fusion Moulding
2. Compression Moulding
Hand molding
is used only in the pharmacy!
Method Fusion Moulding
It involves first melting the suppository base, and
then dispersing or dissolving the drug in the
melted base.
The mixture is poured into a suppository mold.
When the mixture has congealed, the
suppositories are removed from the mold.
The fusion method can be used with all types of
suppositories and must be used with most of
them.
Technological stages of industrial production of
suppositories by fusion moulding
1) Production of bases;
2) Preparation of drugs and obtaining
concentrate;
3) Introduction drugs in the base;
4) Formation (and packing) suppositories;
5) Packing of suppositories.
Stage of production bases:
1. Weighing components of the base.
2. In stainless steel reactor with a steam jacket and
stirrer components of base are alloyed at 6070°C and stirring for 40 minutes.
3. The base is filtered through a druc-filter, using
brass mesh or belting, and analyzed by point of
the melting, solidification and times of total
deformation.
4. Then it is transferred to the hardware
department.
Preparation of drugs and obtaining
concentrate
1. Making of the solution or suspension of
medicines:
- Water-soluble components are dissolved in
water, heated to 45 °C,
- Fat soluble components are dissolved in part of
the molted fat base.
- Substances insoluble in water and base, are
used as suspension:
Pre-crushed medicines are mixed in a reactor
with an equal number of base (or one and
half), heated to temperature of 40-50 °C.
Preparation of drugs and obtaining
concentrate
2. The obtained concentrate is cooled and
grinded by colloid miller or for thermolabile
substances - by three rolls ointment rubber.
Furthermore, for obtaining high quality
suspensions rotary-pulsation apparatus,
rotary-screw pumps and other equipment
can be used.
3. These concentrates are filtered through
calico, and then mixed with the rest of the
base.
Introduction medicines in the bases
Ready to concentrate is poured by the
pump (through a hose caprone sieve)
into reactor (with an anchor stirrer or
turbine) for mixing with the rest of
base.
Stage of formation and packing
suppositories:
Lines such as «Sarong 200 S» with
direct dosing of formed mass in the
cells are formed of
polyvinylchloride films is used for
fesion suppositories with followed
styling of products in bundles.
Sarong/SAAS 6 - AP/VP
Switzerland (Hünenberg)
Sarong/SAAS 6 - AP/VP
Switzerland (Hünenberg)
Sarong/SAAS 6 - AP/VP
Switzerland (Hünenberg)
for PVC/PE and PVC/PVCDC/PE and other thermoforming
materials,
output max. 12.000 supp./h,
two stage (cooling time 16 min. = 2 x 8 min.)
4 format sets for suppositories: 1,07 ml, 1,25 ml, 2,2 ml
and 2,5 ml
jacketed melting vessel 80 ltr. with anchor stirrer,
peristaltic pump D-200,
cooling unit 7500W/h,
knurling, coding, perforation and cutting stations,
Cooling unit with closed water circuit for external
installation.
Stage of formation suppositories:
1. From the two vertical set rolls aluminium foil tapes or
polyvinylchloride films are served.
2. Then both tapes are formed in bowl-like halves, which are
connected in to the complete form and heat-sealed at the
temperature.
At the top of each form hole remains open for filling by a
needle for filling, which pours on molten suppository mass.
Thus, a formed from foil packaging is simultaneously used by
fusion moulds.
3. On the next position packaging is hermetically sealed.
From the two
vertical set rolls
aluminium foil
tapes or
polyvinylchloride
films are served.
Disadvantage of the fusion
method:
1. It's possible a bundle of suppository
mass into separate layers during the
measuring and harden especially in
cases of the insoluble ingredients with
a large density or fluid that are not
mixed with water present.
2. This method is not suitable for
thermolabile substances.
To prevent bundle of suppository
mass:
1. You must to increase the
viscosity of the base.
2. Avoid high temperature at the
fusion of the mass.
3. Carry out mixing of the mass
before fusion in the mould.
The method of compressing is nonthermal method of suppositories producing
by compressing of cooled mass and
crushed the mix of the base and drugs.
Compression Molding
It is a method of preparing suppositories from a
mixed mass of grated suppository base and
medicaments which is forced into a special
compression mold.
The method requires that the capacity of the molds
first be determined by compressing a small
amount of the base into the dies and weighing the
finished suppositories.
When active ingredients are added, it is necessary
to omit a portion of the suppository base, based
on the density factors of the active ingredients.
Compression Molding
1. Suppository mass is usually cooled in the
refrigerator to 3 - 5 °C,
2. Cooled suppository mass is crushed and
sifted.
3. Excipients (lactose, sucrose, aerosil and
starch) are added to the composition of
granules for correction technological
properties.
4. Compression of the suppositories.
The advantages of compressing method:
1. Is the ability to prevent the destruction of
thermostable drugs, lack of sedimentation of the
active ingredient and avoid possible
incompatibility with the molten suppository
base. This method is applicable when using
plastic bases.
2. In production of pressed suppositories do not
need to exert considerable efforts to eject
because the fat particles act as an effective base
oils in the wall layer as a result of severe plastic
leakage.
The advantages of compressing
method:
3. Pressing method is particularly suitable in
the production of suppositories with cardiac
glycosides, some thermostable hormones,
biogenic stimulators, because the
production process to yield high precision
dosing, thermal stability of drugs/
Standardization of suppositories
1. Description
2. Identification and quantitative determination of
active substances and antimicrobial preservatives
3. Average mass and uniformity of mass
4. Disintegration
5. Uniformity of content
6. Melting point or a full strain
7. Dissolution
8. Impurities
9. Microbiological purity
10. If necessary, additional control acid and peroxide
numbers
11. Particle size
Quality control of suppositories:
1- Appearance:
This includes odour, colour, surface condition and shape.
2- Weight Uniformity:
- Weigh 20 suppositories individually. w1, w2, w3….w20
- Weigh all the suppositories together = W.
- Calculate the average weight = W/20.
Limit: Not more than 2 suppositories differ from the average
weight by more than 5%, and no suppository differs from the
average weight by more than 10%.
Quality control of suppositories:
3- Melting range test:
- Determines the time taken by an entire suppository to melt when it is
immersed in a constant temperature bath at 37°C.
-The experiment done by using the USP Tablet Disintegration Apparatus.
Procedure:
1-The suppository is completely immersed in the constant temperature water
bath, and the time for the entire suppository to melt or disperse in the
surrounding water is measured.
- The suppository is considered disintegrated when:
A- It is completely dissolved or
B- Dispersed into its component part.
C- Become soft “change in shape” with formation of core which is not
resistant to pressure with glass rod.
Quality control of suppositories:
4- Liquefaction Time or Softening Time Test:
- In this test a U tube is partially immersed in a constant
temperature bath and is maintained at a temperature between
35 to 37°C.
There is a constriction in the tube in which the suppository is kept
and above the suppository, a glass rod is kept. The time taken for
The glass rod to go through the suppository and reach the
constriction is known as the liquefaction time or softening
time.
- Another apparatus is there for finding “softening time” which
mimics in vivo conditions. It uses a cellophane tube, and the
temperature is maintained by water circulation. Time taken for the
suppository to melt is noted
Quality control of suppositories:
5- Breaking Test (Hardness):
- The breaking test is designed as a method for measuring the
fragility or brittleness of suppository.
1-The suppository is placed in the instrument.
2- Add 600 g; leave it for one min. (use a stop watch).
3- If not broken, add 200 g every one min. until the
suppository is broken.
Calculations:
The hardness of the suppository is calculated by adding the weights
together.
But if the suppository is broken before the end of the last min. the
last weight is canceled.
Quality control of suppositories:
6- Dissolution test:
- By using different types of apparatus such as
wire mesh basket, or dialysis tubing is used
to test for in vitro release from suppositories.
Quality control of suppositories:
7- Stability testing:
-Cocoa butter suppositories on storage, “bloom”; i.e., they form a
white powdery deposit on the surface. This can be avoided by
storing the suppositories at uniform cool temperatures and by
wrapping them in foils.
- Fat based suppositories harden on storage, i.e., there is an
upward shift in melting range due to slow crystallization to
the more stable polymorphic forms of the base.
- The softening time test and differential scanning calorimetry can
be used as stability indicating test methods.
- If we store the suppositories at an elevated temperature, just
below its melting range, immediately after manufacture, the
aging process is speeded up.
Directions of suppositories improving :
1. Lyophilized suppositories
2. Porous suppositories
3. Multilayered suppositories
4. Suppositories with film-coated
5. Painted suppositories