Biochemical Technology Topic: Determination of Dissolution of Acetaminophen Tablets

First, the purpose of the test

1. Master the method for measuring the dissolution of tablets

2. Proper use of dissolution tester

Second, the experimental guidance

After taking a solid preparation such as a tablet, it must be disintegrated and dissolved in the gastrointestinal tract before it can be absorbed through the biofilm. For many drugs, the amount of absorption is usually proportional to the amount of drug that is dissolved from the dosage form. For poorly soluble drugs, dissolution is the main process, so the time limit for disintegration is often not an indicator for judging the extent of absorption of poorly soluble pharmaceutical preparations. For drugs with a solubility of less than 0.1 to 1.0 (g/L), absorption in the body is often affected by the rate of dissolution. The dissolution rate is related to the crystal form and particle size of the drug, and also related to the production process, auxiliary materials and storage conditions of the preparation. In order to effectively control the quality of the solid preparation, in addition to using the in vivo measurement method such as blood concentration method or urine concentration method to estimate the absorption rate, the in vitro dissolution method is a relatively simple quality control method.

The degree of dissolution refers to the rate and extent to which a drug is dissolved from a solid preparation such as a tablet or a capsule in a prescribed solvent. However, in practical applications, the dissolution rate refers only to the extent of drug dissolution within a certain period of time, generally expressed as a percentage of the labeled amount. For example, the dissolution limit of acetaminophen within 30 minutes of the pharmacopoeia is 80% of the labeled amount.

For oral solid preparations, especially those solid preparations which are poorly absorbed in the body, and solid preparations of the treatment doses close to the toxic dose, the dissolution test should be performed as a quality standard.

Third, the experimental content

(1) Basket method

1. The basket is divided into two parts, the basket and the basket shaft, made of stainless steel. The inner diameter of the stainless steel wire mesh is 22.2mm±1.0mm, and the range of the basket rotation must not exceed ±1.0mm.

2. The operating container is a 1000 ml round bottom beaker with a jacket water bath; the temperature of the water bath should be such that the temperature of the solvent in the container is maintained at 37 ° C ± 0.5 ° C. The bottom of the basket is 25 mm ± 2 mm from the bottom of the beaker.

3. The motor is connected to the basket shaft, and the rotation speed can be arbitrarily adjusted at 50 to 200 rpm, and the steady speed error does not exceed ±4%.

4. The instrument should be equipped with 6 sets of operating devices, which can measure 6 samples at a time. The sampling point should be placed at the upper end of the basket from the middle of the liquid surface, 10 mm from the wall of the beaker.

(2) Determination of dissolution of acetaminophen tablets

1. 24 ml of dilute hydrochloric acid and degassed water were added to 1000 ml as a solvent, and 1000 ml of a solvent was weighed and injected into each of the operation vessels, and the temperature was maintained at 37 ± 0.5 ° C. Adjust the basket speed to 100 rpm and stabilize it.

2. Take 6 pieces of test sample, put them into 6 baskets, drop the basket into the container, and start timing immediately. After 30 minutes, take 5ml of the solution, filter it, accurately measure 1ml of the filtrate, add 0.04% sodium hydroxide solution to 50ml, shake well, according to spectrophotometry, measure the absorbance at 257nm wavelength, press C ₈ H ₉ NO ₂ absorption fraction (E1% 1 cm) was 715 to calculate the amount of dissolution per tablet. The limit is 80% of the marked amount and should be in compliance with the regulations.

(3) Judgment of results

The amount of dissolution of each of the 6 tablets, calculated according to the indicated content, should not be lower than the specified limit (Q); unless otherwise specified, the limit (Q) is 70% of the indicated content. If only one of the six sheets is below the specified limit, but not less than Q to 10%, and the average amount of dissolution is not lower than the prescribed limit, it can be judged to be in compliance with the regulations. If one of the 6 tablets is lower than Q-10%, another 6 retests should be taken; only 2 of the 12 samples of the initial and retesting are lower than Q-10%, and the average dissolved amount is not lower than the specified limit. Can also be judged to be in compliance with the regulations.

[Note]

1. Purified water should be added to the water tank of the dissolution apparatus to the water line. After starting the water, the water should be circulated.

2. The solution is filtered through a microporous membrane of not more than 0.8 μm, and self-sampling to filtration should be completed within 30 seconds.

Fourth, thinking questions

1. Why do tablets or capsules of some drugs need to measure dissolution?

2. In order to make the dissolution determination result accurate, what problems should be paid attention to during the experiment?