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Paracetamol Tablet Dissolution Study

The document outlines a practical study on the in-vitro dissolution profile of paracetamol marketed tablets, detailing the objective, methodology, and results. It includes preparation of solutions, calibration curves, and dissolution apparatus procedures, ultimately reporting a percentage drug release of 20.3%. The study emphasizes the importance of dissolution testing in establishing drug safety and efficacy.

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R K Sen
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58 views7 pages

Paracetamol Tablet Dissolution Study

The document outlines a practical study on the in-vitro dissolution profile of paracetamol marketed tablets, detailing the objective, methodology, and results. It includes preparation of solutions, calibration curves, and dissolution apparatus procedures, ultimately reporting a percentage drug release of 20.3%. The study emphasizes the importance of dissolution testing in establishing drug safety and efficacy.

Uploaded by

R K Sen
Copyright
© All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd

PRACTICAL M.

Pharm BPT

Sl. no Titles Page no


01 Dissolution studies of paracetamol marketed tablet 02 - 07
02

1
Sl. No 01.: DISSOLUTION STUDIES OF PARACETAMOL MARKETED
TABLET

Objective: To perform the In-Vitro dissolution profile of paracetamol marketed tablet


and calculate the percentage drug release.

References:
01. Leon Lachman, Leibermann, “The Theory and Practice of Industrial Pharmacy” 3rd
edition, pharmaceutical dosage form, Verghese publishing house (2009), page no. 293 -
345.

Requirements:
• Chemicals: PCM (Dolo 650 or Paracip 650) Tablet, Phosphate Buffer (pH 6.8),
Distilled water.
• Glassware: Volumetric Flask (1000ml, 100ml & 10ml), Beakers with different volume,
Micro pipette, Bulb Pipette
• Apparatus: Dissolution Apparatus 2 - Paddle, UV -Visible spectrophotometer with
matched quartz cells (1cm).

Principle:
Dissolution is pharmaceutically defined as the rate of mass transfer from a solid surface
into the dissolution medium or solvent under standardized conditions of liquid/solid
interface, temperature and solvent composition. It is a dynamic property that changes with
time and explains the process by which a homogenous mixture of a solid or a liquid can be
obtained in a solvent. 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).
The main objective of developing and evaluating an IVIVC is to establish the dissolution
test as a surrogate for human bioequivalence studies, as stated by the Food and Drug
Administration. Analytical data from drug dissolution testing are sufficient in many cases
to establish safety and efficacy of a drug product without in vivo tests, the dissolution
testing which is conducted in dissolution apparatus must be able to provide accurate and
reproductive results. Several dissolute on apparatuses exist. “Dissolution testing is an
essential analytical procedure that's required as part of the final release investigation for
solid oral dosage forms.”

2
Procedure:
Preparation of solutions for Calibration curve:

Stock solution 1: Stock solution of drug (1mg/ml) is prepared by dissolving 20 mg of drug


in 20 ml solution of methanol and phosphate buffer pH 6.8 (in 1:3 ratio) in 20 ml volumetric
flask (to get 1000 µg/ml drug solutions) with vigorous shaking and further sonicated for
about 10 minutes.
Stock solution 2: 10 ml of this (Stock solution 1) is diluted to 100ml with phosphate buffer
pH 6.8 to get a stock solution containing 100 µg/ml of drug. The stock solution was filtered
through Whatman filter paper No. 41.

Dilutions: Take the respective samples (0.1ml, 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1ml, 1.2ml,
1.4ml ….2.2ml, 2.4ml) in each test tube, add phosphate buffer pH 6.8 to make total volume
of 10 ml to produce (1, 2, 4, 6, 8, 10, 12……. 24µg/ml) respectively.

The absorbance of solutions of pure paracetamol drug were measured at 243 λ max and a
calibration curve was plotted between absorbance v/s concentration to get the linearity
and regression equation. (Fig.01)

Phosphate buffer preparation:

Phosphate buffer: Place 50ml of 0.2 M Potassium di -hydrogen phosphate (KH2PO4) in


a 200ml volumetric flask, add the specified volume of 0.2 M sodium hydroxide (NaOH)
and then add distilled water to make up the volume 200ml.

Preparation of 0.2 M Potassium di -hydrogen phosphate solution: Dissolve 27.218g of


potassium di -hydrogen phosphate (KH2PO4) in sufficient distilled water containing in the
1000 ml volumetric flask and to make up to the volume 1000 ml.

Preparation of 0.2 M sodium hydroxide: 8 gm of sodium hydroxide, NaOH in sufficient


distilled water containing in the 1000 ml volumetric flask and make up to the volume 1000
ml.

3
Dissolution Apparatus Procedure:
Before starting the apparatus, it should be set properly.
1. Switch the heater of the dissolution device on and manage the temperature to reach
37°C.
2. Wash the vessel (of dissolution apparatus) using water and then pour 900 ml of
medium (phosphate buffer pH 6.8) in each.
3. Elevate the paddle 25±2 mm from the bottom of the vessel.
4. Operate the paddle on a rotation speed equals to 50 RPM.
5. Add one 500 mg tablet in one vessel which you previously cleaned and at once start
timing.
6. At specified time intervals (10, 20, 30, 40, 50 and 60 min) withdraw 1 ml using the
bulb pipette from each filtrated sample (filtrate) and put it in 10 ml volumetric flask
(clean and neat), then complete the volume up to 10 ml by the medium (phosphate
buffer at pH=6.8).
7. Replace the same volume into dissolution vessel by another volumetric pipette.
8. Read the absorbance of the diluted sample solutions at λ=243 nm using the buffer as
a blank.
9. Plot a graph between Time intervals on x -axis vs % of drug release on y -axis.
10. Find out the slope, concentration, amount of drug release, percentage of drug release
and report it.

Observation:

Image 01.1- From Sl No 01 to 07- Paracetamol in mixed solution of phosphate


buffer 6.8 and Methanol (3:1). From Sl. No 08 to 12- Raw Absorption reading for
paracetamol Dissolution Sample

4
Report:
Absorbance of Paracetamol (pure) at 243nm is reported in the given below table.

Sl. No Conc(𝝁g/ml) Absorption


(x) (y)
1 Blank 0.000
2 2 0.09
3 4 0.295
4 6 0.42
5 8 0.583
6 10 0.719
7 12 0.858
Σ 42 6.802

Table 01.1: Calibration Curve of Paracetamol in mixed solution of phosphate buffer 6.8
and Methanol (3:1) further diluted with phosphate buffer pH 6.8 at λ max 243 nm.

Calibration Curve of PCM (phosphate Buffer: Methanol)


1

0.9

0.8

0.7 y = 0.1471x + 0.165


0.6 R² = 0.996
Absorbance

0.5
Abs
0.4
Linear (Abs)
0.3

0.2

0.1

0
0 1 2 3 4 5 6 7 8
-0.1
Concentration

Graph 01.1- The absorbance of solutions of pure paracetamol drug between absorbance
v/s concentration

5
Calculations

Since, We know that y = mx +c, where, y= absorbance


x= concentrations
So, from the graph, we get y = 0.1471x + 0.165 …. equation (I)

R² = 0.996

Sl. Time Absorption Con. of Con. of Con. Amt. % Of


No. (min) (y) sample sample of of Cumulative
(μg/ml) (mg/ml) 900ml drug Drug
release Release
(A CR) (%CR)
1 10 0.437 0.272 0.002 27.2 24.48 3.76
2 20 0.476 2.114 0.0021 211.4 190.26 29.27
3 30 0.449 1.930 0.0019 193.0 173.7 26.72
4 40 0.383 1.482 0.0014 148.2 133.38 20.50
5 50 0.448 1.925 0.0019 192.5 173.25 26.65
6 60 0.387 1.510 0.0015 151.0 135.9 20.90
Table 01.2: In-vitro Dissolution profile and percentage cumulative Drug Release of
paracetamol Marketed Tablets at PH 6.8

Formulae used in Table 01.2:

a. Con. of sample (μg/ml) by equation (I)


y = 0.1471x + 0.165
or, 0.437= 0.147x + 0.165
0.437−0.165
or, x = 0.1471
or, x = 0.272 𝜇𝑔/𝑚𝑙
b. Con. of sample (mg/ml) = Since 1mg is equal to 1000 𝜇g
𝑥
So, 1000 mg/ml
0.272 𝜇𝑔/𝑚𝑙
= mg/ml
1000

= 0.0002 mg/ml

c. Amount of Drug Release (ACR)


concentration of 900 ml
= x volume of dissolution medium(900ml)
1000
27.2
= 1000 x 900
= 24.48

6
Amount of Drug Release × Dilution Factor(100)
d. % Drug Release (%CR) = Drug Dose(650 mg)
24.48 x 100
= 650
= 3.76

(3.76+29.27+26.72+20.50+26.65+20.90)%
e. Average % of Drug Release = 𝟔

= 20.3%

Result:

The In -Vitro Dissolution profile of Paracetamol marketed tablets were performed, the
percentage of drug release was found to be 20.3%.

Common questions

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Using phosphate buffer at pH 6.8 is critical in mimicking the neutral pH environment of the human small intestine where most drug absorption occurs. It ensures that the dissolution test results can be related to in vivo conditions, facilitating the establishment of a statistically valid IVIVC. This choice of solvent thus ensures that in vitro results have real-life applicability, ensuring the relevance of dissolution testing for bioequivalence assessments .

The preparation involves dissolving 27.218g of potassium dihydrogen phosphate (KH2PO4) in distilled water in a 1000 ml volumetric flask and then adjusting the volume to 1000 ml. Similarly, 8g of sodium hydroxide is dissolved in water in another 1000 ml flask to make 0.2 M NaOH. These components are mixed appropriately to achieve the desired pH of 6.8, critical for standardized dissolution testing .

The calibration curve's reliability is supported by its linear regression equation y = 0.1471x + 0.165 with an R² value of 0.996. The R² value indicates a very strong correlation between absorbance and concentration, suggesting that the model explains most of the variability in the data. This high degree of correlation confirms the validity and accuracy of the calibration curve, making it a robust tool for predicting unknown concentrations in further analyses .

The calibration curve enables the determination of the concentration of paracetamol in solution through the relationship between absorbance and concentration. With absorbance measured at 243 nm for different concentrations, the linear regression equation derived from the curve allows calculation of unknown concentrations during the dissolution test, providing accurate and reproducible data necessary for assessing drug release .

Time intervals, such as those at 10, 20, 30, 40, 50, and 60 minutes, facilitate the plotting of a time vs. percentage drug release curve, allowing researchers to observe the kinetics of drug release. These intervals help in calculating the cumulative drug release percentage, observationally confirming the dissolution rate and identifying the release pattern, which is crucial for correlating with in vivo scenarios and verifying the IVIVC .

Using UV-Visible spectrophotometry at 243 nm takes advantage of paracetamol's specific absorbance properties, maximizing sensitivity and accuracy in quantifying drug concentration. This wavelength allows for precise measurement of absorbance, directly linked to the concentration through the calibration curve, thus ensuring reliable determination of drug release over time in the dissolution medium .

The dissolution rate of paracetamol is influenced by several factors including the liquid/solid interface, temperature, solvent composition, and the standardization of dissolution conditions. The rate is defined by the mass transfer from a solid surface into the dissolution medium under these conditions. These factors ensure that the dissolution process can be accurately correlated with in vivo pharmacokinetic data, fulfilling the criteria set by the FDA for establishing dissolution tests as surrogates for human bioequivalence studies .

In vitro-in vivo correlation (IVIVC) serves as a bridge linking pharmaceutical formulation with its clinical performance. It allows the dissolution test to act as a substitute for human bioequivalence studies, thereby reducing the need for extensive clinical trials. This is particularly useful for ensuring that modifications in the formulation do not affect therapeutic efficacy. As per FDA standards, a robust IVIVC can lead to cost-effective drug development while ensuring safety and efficacy through predictive dissolution testing .

Temperature control at 37°C aligns with human body temperature, ensuring that the dissolution environment parallels physiological conditions. This precision is crucial for maintaining consistent kinetic rates and accurate dissolution readings. Inconsistent temperatures could lead to variability in dissolution rates, affecting data integrity and compromising the IVIVC link, hence the need for precise temperature management in dissolution assays .

The paddle method in dissolution apparatus provides a standardized mechanical environment where a consistent 50 RPM speed and a controlled temperature of 37°C mimic physiological conditions. This ensures uniform agitation and heat distribution, facilitating consistent mass transfer from solid to liquid phase. The precise control of these parameters helps in achieving reproducible and reliable dissolution profiles, thereby supporting the assessment of drug release and solubility characteristics .

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