Tablet Dissolution Test - Determination of Dissolution Rate and Dissolution Rate of Azithromycin Dispersible Tablets

The determination of the dissolution rate and dissolution rate of azithromycin dispersible tablets is mainly to ensure the effectiveness and safety of the drug. The in vivo release and absorption characteristics of the tablets are evaluated through in vitro experiments to ensure the stability of the preparation quality and compliance with pharmacopoeia and regulatory requirements.

Experimental Principle

After ingestion, solid dosage forms such as tablets undergo two processes in the gastrointestinal tract: disintegration and dissolution. These processes are then absorbed across biological membranes. For many drugs, the amount absorbed is generally proportional to the amount dissolved from the dosage form. However, for poorly soluble drugs, dissolution is the primary process, so the disintegration time is often not a reliable indicator of the absorption rate of poorly soluble drug formulations. For drugs with solubility less than 0.1-1.0 g/L, in vivo absorption is often influenced by their dissolution rate. This dissolution rate is not only related to the drug's crystal form and particle size, but also to the formulation's manufacturing process, excipients, and storage conditions. To effectively control the quality of solid dosage forms, in vitro dissolution testing offers a relatively simple quality control method, in addition to in vivo methods such as blood or urine drug concentrations to estimate absorption rates.

Dissolution refers to the rate and extent of drug dissolution from solid dosage forms such as tablets and capsules in a specified solvent. However, in practical applications, dissolution refers only to the extent of drug dissolution within a specified timeframe, generally expressed as a percentage of the labeled amount. For example, the pharmacopoeia stipulates that the dissolution limit of azithromycin within 30 minutes is 75% of the labeled amount. Dissolution rate, on the other hand, refers to the amount of dissolution measured at various time points. The calculated dissolution rate at each time point and per unit time exhibits a certain pattern, and the corresponding parameter can be determined based on different treatment methods.

The solid preparation dissolution data processing methods are as follows: ① single exponential model: ② Weibull distribution model.

For oral solid preparations, especially those poorly soluble solid preparations that are poorly absorbed in the body, as well as solid preparations of drugs with therapeutic doses close to toxic doses, dissolution tests should be performed and used as quality standards.

Instruments and Reagents

Instrument

Dissolution tester, Model 7200 visible spectrophotometer, 0.45µm microporous filter.

Reagents

Azithromycin dispersible tablets, phosphate buffer, 14mol/L concentrated sulfuric acid.

Experimental Procedure

1. Preparation of Buffer

Adjust the pH of 0.1 mol/L sodium hydrogen phosphate solution to 6.0 ± 0.05 with hydrochloric acid.

2. Preparation of Stock Solution

Take 10 dispersible tablets and accurately weigh them to calculate the average tablet weight (W). Grind the weighed tablets finely. Accurately take an amount equivalent to W and place it in a 250 mL volumetric flask. Add phosphate buffer to the mark, mix, and dissolve in a 37 °C water bath with shaking for 15 minutes. Filter through a 0.45 µm microporous filter to obtain the solution (c = 1000 µg/mL).

3. Plotting the Standard Curve

Dilute 1.00mL, 2.00mL, 4.00mL, 6.00mL, 8.00mL, and 10.00mL of the above stock solution to 100mL, yielding solutions with concentrations of 10µg/mL, 20µg/mL, 40µg/mL, 60µg/mL, 80µg/mL, and 100µg/mL. Pipette 5.00mL of each of these solutions into a 100mL beaker, add 5.00mL of 4 mol/L concentrated sulfuric acid, shake well, and let stand at room temperature for 30 minutes. Cool to room temperature and measure the absorbance at 482nm. Plot a standard curve with absorbance as the y-axis and concentration as the x-axis (linear regression can be performed using a calculator).

4. Determination of Dissolution Rate

(1) Add distilled water to the water bath to the mark.

(2) Adjust the temperature to 37.5℃ and start the water pump.

(3) Take 1000mL of phosphate buffer, heat it to (37±0.5) °C, and pour it into the storage tank.

(4) After adjusting the temperature, adjust the speed to 100r/min at (37±0.5) °C and stop the rotation.

(5) Take 6 tablets and place them in 6 rotating baskets respectively. Start the timer when the phosphate buffer contacts the tablets.

(6) Then take samples at 1min, 3min, 5min, 7min, 9min, 12min, 15min, 20min, and 30min (the sampling position is fixed in the middle of the rotating basket, not less than 1cm away from the wall of the cup). Take 5mL of sample each time and immediately add 5mL of phosphate buffer [(37±0.5)℃] to the storage tank.

(7) Add 0.45 After filtration through a µm microporous filter, take 2.00 mL of the filtrate into a stoppered measuring cylinder, pipette 3.00 mL of phosphate buffer to dilute, add 5.00 mL of 14 mol/L sulfuric acid, shake well, and let stand at room temperature for 30 min, then cool to room temperature.

(8) Pipette 5.00 mL of phosphate buffer and make a blank control according to method (7). Measure their absorbance at 482 nm.

Experimental Results

1. Plotting the Standard Curve

Data are shown in Table 1.

Table 1 Standard Curve Determination Data

2. Dissolution Determination

The results are shown in Table 2.

Table 2 Dissolution Determination Results of Azithromycin Dispersible Tablets

3. Dissolution Rate Determination

a. Experimental Data

The results are shown in Table 3.

Table 3 Dissolution Rate Determination Data for Azithromycin Dispersible Tablets

b. Plot

Plot the residual volume to be dissolved versus t.

c. Determine the dissolution rate constant from the slope of the line.

K = -2.303 x slope

Frequently Asked Questions (FAQs)