University of Jordan Faculty of Pharmacy Practical Pharmaceutical Technology I USP Dissolution Method for PARACETAMOL 500 mg Tablets Section No. 6 Group D
USP Dissolution Method for PARACETAMOL 500 mg Tablets Introduction: 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 wellestablished predictive IVIVC model can be very helpful for drug formulation design and postapproval 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: USP Dissolution Apparatus 1 - Basket (37 C) Dissolution Apparatus 2 - Paddle (37 C) USP Dissolution Apparatus 3 - Reciprocating Cylinder (37 C) USP Dissolution Apparatus 4 - Flow-Through Cell (37 C) USP Dissolution Apparatus 2 is the most widely used apparatus among these four. 1
Objectives: 1- Applying the USP dissolution method to Revanin 500 mg tablets. 2- Comparing the calculated %Dissolved for Revanin 500 mg tablets to USP references values (Tolerance, Q). Procedure: 1- Switch the heater of the dissolution device on and manage the temperature to reach 37ᵒC. 2- Wash two of the vessels using water and soap then put 900 ml of medium (phosphate buffer) 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 Revanin 500 mg tablet in each vessel which you previously cleaned and at once start timing. 6- After passing half an hour take 5 ml sample from each vessel by the mean of volumetric pipette, then filter the two samples using filter paper and wetted by the buffer medium (to get rid of any un-dissolved particles that might be found in the samples) by filter paper, always get rid of the first milliliter to avoid below estimation of the concentration, because filter paper will be saturated with the drug. 7- Withdraw 1 ml using the volumetric pipette from each filtrated sample (filtrate) and put it in 50 ml volumetric flask (clean and neat), then complete the volume up to 50 ml by the medium (phosphate buffer at ph=5.8. 8- Read the absorbance of the diluted sample solutions at λ=243 nm using the buffer as a blank. Results: Samples: Absorbance at λ=243 nm Sample (1) 0.668 Sample (2) 0.648 Standard Solutions Concentrations (mg%): Absorbance at λ=243 nm* 0.5 0.202 1 0.551 1.5 0.913 2 1.245 (*) Our real absorbance values are out of the linear range due to error during dilution, and these values are obtained from another experiment. 2
Absorbance Calculations: Sample: Concentration Total Amount Dissolved In 900 % Dissolved * (mg%): ml Sample (1) 1.16 524 mg 104.8 % Sample (2) 1.14 511 mg 102.2 % (*) Acetaminophen tablets contains not less than 90% and not more than 110% of the labeled amount of acetaminophen by USP recommendations 1.400 1.200 Calibration Curve of Acetaminophen in Phosphate buffer ph=5.8 at λ=243 y = 0.6982x - 0.145 R² = 0.9997 1.000 0.800 0.600 0.400 0.200 0.000 0 0.5 1 1.5 2 2.5 Paracetamol Concentration (mg% w/v) 3
Dilution Factor Observation: The tablets disintegrated within minutes after starting the experiment by using the Dissolution Apparatus and then converted into small granules which dissolved at the end of the experiment. Conclusion: After all the experiment is done and we've done the calculations to know the amount of paracetamol dissolved, we notice that it's above the tolerance ratio which in our case is 80%, therefore it passed the dissolution test. 4