This document summarizes the dissolution studies of paracetamol commercial tablets conducted to determine the percentage of drug release over time. The study involved preparing standard solutions to generate a calibration curve, performing the dissolution test using the paddle apparatus, and calculating the percentage of drug released at various time points up to 60 minutes. The results showed that the percentage of paracetamol released was [VALUE] at 60 minutes.
This document summarizes the dissolution studies of paracetamol commercial tablets conducted to determine the percentage of drug release over time. The study involved preparing standard solutions to generate a calibration curve, performing the dissolution test using the paddle apparatus, and calculating the percentage of drug released at various time points up to 60 minutes. The results showed that the percentage of paracetamol released was [VALUE] at 60 minutes.
This document summarizes the dissolution studies of paracetamol commercial tablets conducted to determine the percentage of drug release over time. The study involved preparing standard solutions to generate a calibration curve, performing the dissolution test using the paddle apparatus, and calculating the percentage of drug released at various time points up to 60 minutes. The results showed that the percentage of paracetamol released was [VALUE] at 60 minutes.
This document summarizes the dissolution studies of paracetamol commercial tablets conducted to determine the percentage of drug release over time. The study involved preparing standard solutions to generate a calibration curve, performing the dissolution test using the paddle apparatus, and calculating the percentage of drug released at various time points up to 60 minutes. The results showed that the percentage of paracetamol released was [VALUE] at 60 minutes.
Instrumentation: USP Dissolution Apparatus 2 - Paddle, UV-Visible spectrophotometer with
matched quartz cells (1 cm)
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 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 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 dissolution apparatuses exist. In United States Pharmacopeia (USP), there are four dissolution apparatuses standardized and specified they are:
1. USP Dissolution Apparatus 1 - Basket (37°C)
2. USP Dissolution Apparatus 2 - Paddle (37°C) 3. USP Dissolution Apparatus 3 - Reciprocating Cylinder (37°C) 4. USP Dissolution Apparatus 4 - Flow-Through Cell (37°C) 5. USP Dissolution Apparatus 2 is the most widely used apparatus among these four. PROCEDURE:
Preparation of solutions for Calibration curve:
Stock solution 1: Stock solution of drug (1mg/ml) is prepared by dissolving 100 mg of drug in 100 ml solution of methanol and phosphate buffer pH 6.8 (in 1:3 ratio) in 100 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 Whatmann filter paper No.41. Date: ……………… Experiment No: 3 Page no: 2
Dilutions: Take the respective samples (0.2ml, 0.4ml, 0.6ml, 0.8ml, 1ml, 1.2ml, 1.4ml, 1.6ml, 1.8ml, 2ml, 2.2ml, 2.4ml) in each test tube, add phosphate buffer ph 6.8 to make total volume of 10 ml to produce (2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24µg/ml) respectively.
Determination of absorption maxima:
A UV absorption maximum was determined by scanning 10µg/ml solution of paracetamol in
phosphate buffer 6.8, in between 200-400 nm by using UV-visible spectrophotometer. Further a representative spectrum was drawn of paracetamol in phosphate buffer pH 6.8.
Preparation of Calibration curve:
The standard solutions for the drug having concentration 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 24µg/ml was prepared with phosphate buffer ph 6.8 from the stock solution. 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 which has shown in fig. 2.
Phosphate buffer preparation:
Phosphate buffer: Place 50ml of 0.2 M Potassium di-hydrogen phosphate in a 200ml volumetric flask, add the specified volume of 0.2 M sodium hydroxide (given in the table) 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 in sufficient distilled water containing in the 1000ml volumetric flask and to make up to the volume 1000ml.
Preparation of ‘x’ M sodium hydroxide: Solution of any molarity ‘x’ Molar may be prepared by dissolving 40*x gms of sodium hydroxide in sufficient distilled water containing in the 1000ml volumetric flask and make up to the volume 1000ml.
Dissolution study procedure:
1. Switch the heater of the dissolution device on and manage the temperature to reach 37ᵒC. 2. Wash the vessel (of dissolution apparatus) using water and soap then put 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 (5, 10, 15, 20, 25, 30, 45 and 60 min) Withdraw 1 ml using the volumetric 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.
Calculations for calibration curve of pure paracetamol drug
UV Spectrum of Paracetamol:
Fig. 2: Calibration curve of Paracetamol in mix solution of phosphate buffer 6.8 and Methanol (3:1) further diluted with phosphate buffer 6.8 at λ max 243 nm Date: ……………… Experiment No: 3 Page no: 4
Table for specified volume of NaOH required preparing buffer solutions:
