Diffusion cell method is a reliable and reproducible method for in vitro release test (IVRT) of semi-solid dosage forms. The United States Pharmacopoeia (USP) < 1724 > SEMISOLID DRUG PRODUCTS—PERFORMANCE TESTS contains the specific determination methods and requirements of diffusion cell method.

Cream is an ointment made of emulsion matrix. It has the characteristics of good drug release and penetration, improving local drug concentration and not hindering the normal function of skin. It is a commonly used dosage form in clinic.

This article will share the in vitro release test case of an cream preparation using diffusion cell method, hoping to bring you help and inspiration.

Experimental Instrument: RT800 Automatic Sampling Transdermal Diffusion System

Apparatus: Raytor improved Franz vertical diffusion cell

Temperature: 32 ± 0.5 ℃

Medium: technical confidentiality

Rotational Speed：600 RPM

Artificial Membrane: technical confidentiality

Sample Loading Amount: ~ 0.3 g

Medium Volume: 30 mL

Sampling / Replenishment Volume: 1 ml

Diffusion Cell Orifice Diameter: 15 mm

Orifice Area of Diffusion Cell: 1.77 cm

Testing Process

Medium Volume

Weigh the medium added to the diffusion cell, and calculate the volume of the medium according to the measured medium density:

According to USP < 1724 >, all diffusion cells during the test shall have the same  volume, and the real volume of each diffusion cell shall be measured. Although USP < 1724 > does not explicitly require the error range of medium volume, we suggest that the error of medium volume should not exceed 1%.

Sample Loading Amount

Weigh and record the amount of cream in the sample loading ring, and make sure that the amount of cream is within the normal range.

According to USP < 1724 >, the sample quantity tested by diffusion cell method is generally not less than 0.2g. Although the loading amount of the sample does not participate in the calculation of the cumulative drug release, the weighing data beyond the normal range can reveal possible abnormal sample loading, such as bubbles remaining between the cream and the filter membrane.

Type of Membrane

Appropriate inert and commercial artificial membranes should be selected for the in vitro release of semi-solid preparations. Commonly used membranes include polyethersulfone, cellulose acetate, nylon mixed ester and polytetrafluoroethylene membrane. Cellulose acetate is a hydrophilic membrane, which is not tolerant to organic solvents. Therefore, when the release medium contains organic solvents, the other three membranes are the better choice.

Automatic Sampling

According to USP < 1724 >, the sampling shall be completed within ± 2 min of the sampling time specified in the method. RT800 automatic sampling transdermal diffusion system can automatically complete the sampling of six diffusion cells at the same time, without the problem of sampling time difference.

Test Result

According to USP < 1724 >, calculate the cumulative amount released per 1 square centimeter of orifice area at each sampling time point:

The relative standard deviation (RSD) of the cumulative release of six test samples in 24 hours is 1.53%. The repeatability of this test is good.

The release of drugs in cream generally follows higuch formula, that is, the cumulative release of drugs is directly proportional to the square root of time.

The cumulative drug release of six test samples at each sampling time point is linearly regressed with the square root of the sampling time to obtain the regression equation and correlation coefficient, and the slope value is taken as the drug release rate constant.

Result Discussion

The results show that the diffusion cell method has high precision and good reproducibility. It can be used to distinguish the differences of different cream formulations, and provide valuable in vitro release measurement data for the formulation development of cream products.

Thanks to the high-precision automatic design of RT800 automatic sampling transdermal diffusion system, the error introduced by the experimental system or manual operation is effectively reduced, making the repeatability of the test results more ideal.