EXPERIMENT : 3

DISSOLUTION STUDY OF MARKATED PARACETAMOL IP

 AIM : To perform the Dissolution Study of marketed Paracetamol IP.

 THEORY : Dissolution is a process in which a solid substance solubilises in a

given solvent i.e., mass transfer from solid surface to the liquid phase.

In the body , a pharmaceutical active ingredient must be “ in solution” before it can be

absorbed by the blood and ultimately carried to the receptor site to render a therapeutic effect
(in vivo) .

Dissolution is the process by which the active ingredient enters into solvent to yield a
solution.
Rate of dissolution is the amount of drug substance that goes in solution per unit time
under standardized conditions of liquid/solid interface , temperature and solvent
composition.

A main purpose of solid dosage form is to make available to the human body a certain and
defined amount of the active substance through the gastrointestinal system. Studies on the
bioavailability of drugs from a given dosage form revealed that , in many situations , solid
dosage forms with the same therapeutic effect. This fact is ascribed to differences in
physical characteristics of the active compound in formulation factor or in technological
processes used by different manufacturers , resulting in different bioavailability profiles.
Pharmaceutical availability or in vitro availability is one of aspects of drug bioavailability. Of
the tests that can be performed on drug solid is the dissolution test is considered to be
sensitive , reliable and rational for predicting in vivo drug bioavailability behavior.

Figure 1 : Dissolution.

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  DISSOLUTION TEST : A dissolution test is an in vitro analytical test used for
assessing expected drug release characteristics of pharmaceutical products in humans,
in particular , of solid oral dosage forms , such as tablets and capsules.

Dissolution tests ate to determined drug release patterns , Physiological availability ,

and Bioavailability of formulated products.

Dissolution study is useful for the therapeutical effectiveness of the drug at different
locations of the human body.

In the pharmaceutical industry, drug dissolution testing is routinely used to provide critical in
vitro drug release information for both quality control purposes, to assess batch-to-batch
consistency of solid oral dosage forms such as tablets, and drug development to predict in
vivo drug release profiles.
In vitro drug dissolution data generated from dissolution testing experiments can be
related to in vivo pharmacokinetic data by means of in vitro-in vivo correlations
(IVIVC). A well- established predictive IVIVC model can be very helpful for drug
formulation design and post- approval manufacturing changes.
The dissolution testing which is conducted in dissolution apparatus must be able to provide
accurate and reproducible results.

Several dissolution apparatus exist.

ROTATING
USP APPARATUS TYPE USE SPEED

Apparatus I Rotating Basket Tablets , Capsules. 50 – 120 rpm

Tablets , Capsules ,
Apparatus II Paddle Modified release 25 – 50 rpm
solid dosage form
Reciprocating Extended release
Apparatus III Cylinder products 6 – 35 rpm

Apparatus IV Flow Through Cell Poorly soluble N/A

drugs

Apparatus V Paddle Over Disc Transdermal Patch 25 – 50 rpm

Apparatus VI Rotating Cylinder Transdermal Patch N/A

Apparatus VII Reciprocating Disc Transdermal Patch 30 rpm

Table : 1

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 Figure 2 : USP Apparatus.

Figure 3 : USP Apparatus 2.

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  MATERIALS REQUIRED :
Chemicals : Paracetamol pure drug , Phosphate buffer pH 6.8 , Distilled water.
Instrumentation : Dissolution Apparatus 2 – Paddle ,
UV-Visible spectrophotometer (SHIMADZU) with matched quartz cells (1 cm).

Glassware : Volumetric flasks-1000ml , 10ml , beakers, pipettes , Thermometer , Filter

Paper , e.t.c.

 4

Figure 4 : LABINDIA 8000 (Dissolution Apparatus)

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 METHODOLOGY:

1) Phosphate Buffer Preparation: 28.80 gm of disodium hydrogen phosphate and

11.45 gm potassium di-hydrogen phosphate are taken in different beaker and
dissolved in few ml of water. If two solutions are not properly dissolved apply gentle
heat. Then two solution are transfer into a 1000 ml volumetric flask and the volume
made up to 1000ml by using water.
2) Accurately transfer 900ml of dissolution media (phosphate buffer 6.8) to each 6
dissolution vessel
3) Place the heater into the dissolution vessel until it get the temperature 37°C.

4) Place one tablet into each of six dissolution vessel and operates at 50 rpm.

5) At the end of 5,10,15,20,25,30,35,40,45,50,55,60 mintues withdraw 10 ml allquot

from each vessel and fresh 10 ml to maintain sink condition.

6) Filter each allquot immediately through 0.45 micron membrane filter .collect the
filtrate for analysis.

7) Set the wavelength range at 200-400 nm and measure the absorbance at 243nm of
each sample.

8) Plot the graph .

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 RESULT :

Absorbance Of
% drug release
Sl No Time Absorbance Std
1 0 O 0 0
2 5 0.112 0.919 12.817
3 10 0.221 0.919 24.048
4 15 0.248 0.919 26.986
5 20 0.321 0.919 34.929
6 25 0.382 0.919 41.567
7 30 0.420 0.919 43.743
8 35 0.442 0.919 48.096
9 40 0.521 0.919 56.692
10 45 0.581 0.919 63.221
11 50 0.611 0.919 66.485
12 55 0.752 0.919 81.828
13 60 0.772 0.919 84.004
Table : 2

Cumulative % Cumulative % Drug Log Cumulative Square Root

Drug Release Remain % Drug Remain Of Time
0 0 0 0
12.187 87.813 1.944 2.236
24.116 75.884 1.880 3.162
27.120 72.880 1.863 3.873
35.080 64.920 1.812 4.472
41.762 58.238 1.765 5.000
43.975 56.025 1.748 5.477
48.340 51.660 1.713 5.916
56.961 43.039 1.634 6.325
63.537 36.463 1.562 6.708
66.838 33.162 1.521 7.071
82.199 17.801 1.250 7.416
84.461 15.539 1.191 7.746
Continuation of Table 2

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Figure 4 : Zero Order Graph.

Figure 5 : Higuchi Plot.

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  DISCUSSION : After the experiment, observed that it shows standard curve in
lamda max 243 nm and regression coefficient is 0.9972 and follows Zero Order
Kinetics.

 CONCLUSIONS : After the performing the experiment , it conclude that the

standard curve of paracetamol shows at lamda max 243 nm and Regression
Coefficient is 0.9972 respectively and follows Zero Order Kinetics.

 ACKNOWLEDGEMENT : I would like to express my gratitude to Dr. Raja

Majumdar, Mr. Soumyodip Ghosh, Mrs. Trisha Chatterjee & Mr. UtpalMisra for their
guidance and support.

 REFERENCES :

1. India. Pharmacopoeia of India (the Indian Pharmacopoeia). 3rd ed. Delhi: Controller
of Publications; 1985.

2. L Lachman, HA Lieberman, and JL Kanig: The Theory and Practice of Industrial

Pharmacy, Varghese publishing house 3rd Edition, 1986; 296-300

3. Lachman Leon Herbert A. Lieberman and Joseph L. Kanig. 1976. The Theory and
Practice of Industrial Pharmacy. 2d ed. Philadelphia: Lea&Febiger.pg(99-120)

4. Allen L. V and Ansel H. C. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug
pp(230- 300)

Signature Of the Student Signature of the Faculty

Date:

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