THE EFFECT OF pH ON SOLUBILITY OF DRUGS
M.SWETHA*,CH. KALYANI, GANESH KUMAR.G,SANTHOSH KUMAR.M
Srikrupa institute of pharmaceutical sciences,
vil: velkatta, Mdl: kondapak, dist: medak, andhra pradesh - 502277
MATERIALS:
KEYWORDS:
Nimesulide,
solubility, various pH Media, phosphate
buffer.
INTRODUCTION
A
Biopharmaceutical
Classification
System (BCS) has been recently
proposed for drug product bioequivalence
requirements.
Solubility
and
permeability, the key parameters in BCS ,
play important roles in the development
of formulations and regulatory standards.
Particularly for water insoluble drugs that
have
generally
high
membrane
permeability ( BCS Class II) , dissolution
and dose are the most critical factors
affecting the rate and the extent of oral
absorption. It is well known that
dissolution
is
affected
by
the
environmental
changes
in
the
gastrointestinal tract such as pH,
surfactant, ionic strength, buffer capacity,
or viscosity.
STRUCTURE OF NIMESULIDE:
Preparation of 0.01N Hydrochloric acid:
Nimesulide is obtained as gift sample
from B & T PHARMACEUTICALS,
Hyderabad, Hydrochloric acid, Sodium
Hydroxide,
Potassium
dihydrogen
phosphate are procured of S D FINE
CHEMICALS LIMITED, Mumbai.
METHOD:
Preparation
of
standard
graph:
Accurately100 mg of Nimesulide was
dissolved in small amount of 0.2N
Sodium hydroxide in a 100 mL
volumetric flask and volume adjusted up
to 100 mL with sodium hydroxide. From
this solution 10 mL was taken and diluted
upto 100 mL in a100 mL volumetric flask
with 0.2N sodium hydroxide . Beers
range was found and the five
concentrations of 2, 4, 6, 8, 10 and 12
μg/mL were prepared and the absorbance
was checked at a 277nm. Finally graph
plotted by taking concentration on X-axis
and absorbance on Y-axis and calibration
curve was plotted.
0.909 mL of conc Hydrochloric acid was
dissolved in 1000 mL of water . It contain
0.01N Hydrochloric acid.
Preparation of 0.1N Sodium Hydroxide:
4 g of Sodium hydroxide was dissolved in water
and volume make upto 1000 mL with water . It
contain 0.1 N sodium hydroxide.
Preparation of 0.01N Sodium Hydroxide:
0.4 g of Sodium hydroxide was dissolved in
water and volume make upto 1000ml with
water . It contain 0.01 N sodium hydroxide.
PROCEDURE:
10 ml of 0.01 N HCl, 0.1N HCl, 5.8 Phosphate
buffer, 6.8 Phosphate buffer, Distilled water, 7.4
Phosphate buffer, 0.01N NaOH, 0.1N NaOH
mediums is taken in different vials. Then add
100mg drug to the medium.
RESULTS & DISCUSSION:
Graph depicting the amount of nimesulide solubilized in 10 mL
of the selected media
378.34
400
Standard curve of nimesulide in 0.2N NaOH at L-max 391.4 nm
350
Amount Solubilized (mg)
In this study report the results of the
effect of pH on the solubility of
Nimesulide (BCS poorly soluble drug) in
physiological pH. Some drugs having
poor bioavailability are with poor
aqueous solubility and or slow dissolution
rate in the biological fluids. The solubility
of drug is different in pH of various areas
of Gastro Intestinal Track. Nimesulide is
a selective cox-2 inhibitor having poor
aqueous solubility so its solubility has to
be enhanced. The solubility profile of
Nimesulide was investigated over a broad
pH ranges. The solubility of the
Nimesulide was measured in the pH
range from 0.01N HCl , 0.1N HCl , 5.8
phosphate buffer, 6.8 pH phosphate
buffer, distilled water, 7.4 pH phosphate
buffers, 0.01N NaOH , 0.1N NaOH . The
solubility of the Nimesulide is increased
with increasing pH . The results obtained
in this experiment conclude that the
Nimesulide solubility was at high pH and
suggest formulator to develop dosage
form which releases the drug in intestine
for any modified activity. And also for
the development of solution type of
formulations suitable for oral, topical or
parenteral delivery.
Nimesulide is a unique non- steroidal
anti-inflammatory
drug
that
acts
specifically on cyclo-oxygenase-2 and
does not affect cyclo-oxygenase-1.
Hence, it exerts its anti-inflammatory
action characteristics of non- steroidal
anti-inflammatory drug but shows a
marked increase in gastric tolerability and
minimal incidences of renal dysfunction.
Due to its additional action of inhibiting
respiratory burst of phagocytosing
neutrophils it is also well tolerated by
asthmatic patients. Hence, it is one of the
most commonly prescribed non- steroidal
anti-inflammatory drugs for the treatment
of various inflammatory conditions such
as tonsillitis, pharyngitis, stomatitis,
rheumatoid arthritis, osteoarthritis, low
back pain. A variety of Nimesulide
preparations are available in the market
in the form of tablets and syrup for oral
administration and gels for topical
application.
Like many non- steroidal antiinflammatory drug, Nimesulide is
insoluble in water. The very poor
aqueous solubility and wettability of the
drug give rise to difficulties in the
pharmaceutical formulation of oral or
parenteral solutions and may lead to a
variable bioavailability. The present work
investigates the solubility enhancement
and hence bioavailability of the drug.
Solubility of drug can be increased by
variety of contemporary methods.
Nimesulide,
chemically
4’-nitro-2’phenoxy methane sulfonanilide , is a
weakly acidic (pKa 6.5) nonsteroidal
anti-inflammatory drug (NSAIDs). It
differs from other nonsteroidal antiinflammatory drugs in that its chemical
structure contains a sulfanilide moiety as
the acidic group rather than a carboxylic
group .
0.5
0.45
y = 0.0434x
R2 = 0.9995
0.4
0.35
0.3
Abs
ABSTRACT:
Series1
0.25
Linear (Series1)
0.2
300
250
200
150
80.55
100
0.042 0.126
0.216
0.405
0.251
0.806
50
0
0.15
0.1 N
HCl
0.1
0.01N
HCl
PB pH
5.8
PB pH
6.8
DW
PB pH
7.4
0.01 N
NaOH
0.1 N
NaOH
Media
0.05
0
0
2
4
6
8
10
12
Conc (mcg/mL)
Preparation of Phosphate buffer:
50 ml of 0.2M Potassium dihydrogen
phosphate in a 200ml volumetric flask,
add the specified volume of 0.2M Sodium
hydroxide. Then add water to volume.
pH
5.8
6.8
7.4
0.2M NaOH
3.6
22.4
39.1
CONCLUSION:
The solubility of the Nimesulide is increased
with increasing pH . The results obtained in
this experiment conclude that the Nimesulide
solubility was at high pH and suggest
Formulator to develop dosage form which
releases the drug in intestine for any
modified activity. And also for the
development of
solution
type
of
formulations suitable for oral ,topical or
parenteral delivery.
REFERENCES:
Preparation of 0.2 M potassium dihydrogen
phosphate:
Dissolve
27.218g
of
potassium
dihydrogen phosphate in water and dilute
with water to 1000 mL .
Preparation of 0.1N Hydrochloric acid:
9.09 mL of conc Hydrochloric acid was
dissolved in 1000 mL of water . It contain
0.1N Hydrochloric acid.
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and Family Welfare. The Pharmacopoeia of
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1996.
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pharmacy, 3rd ed.Varghese publishing house.
1987, 67.
3.Higuchi T. Mechanism of sustained-action
medication: theoretical analysis of rate of
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