Synthetic membrane selection for in vitro release testing (IVRT): A case study of topical mometasone furoate semi-solid dosage forms

Abstract

In vitro release testing (IVRT) is extensively used to develop the formulation of topical semi-solid products, to evaluate the quality and consistency of the product after scale-up and post-approval changes, and more recently to aid the evaluation of topical generic products’ equivalency. The selection of synthetic membrane is one of the most critical parameters of the method development part of IVRT. It is well known that the membrane features namely its polymer matrices, porosity, pore size, thickness can have a substantial effect on the IVRT data. However, there is no detailed information available in the literature regarding the membrane selection for different types of topical dosage forms. Therefore, we aimed to investigate whether difference topical semi-solid dosage forms of the same drug molecule would cause to variation in the membrane selection. Within this framework, rheological behaviour of commercially available three different types of topical semi-solid dosage forms (ointment, cream, and lotion) of mometasone furoate (0.1%) were primarily characterized. Then, the membrane inertness test was conducted using a series of synthetic hydrophilic membranes (regenerated cellulose, cellulose acetate, cellulose nitrate, mixed cellulose ester membranes) and hydrophobic membranes (polyether sulfone, polypropylene, polytetrafluoroethylene membranes) after identifying of an appropriate receptor medium that ensures sink condition for mometasone furoate. Lastly, IVRT studies from the topical semi-solid products were performed utilizing Franz-type diffusion cells. The membrane inertness and in vitro release data demonstrated that the cellulose acetate membrane showed superior diffusion properties in general while the other synthetic membranes exhibited varying outcomes for different semi-solid dosage forms of mometasone furoate. Overall, the results indicated that the release rate and the cumulative drug released amount of drug after 6 h through the different synthetic membranes might vary depending on the semi-solid dosage form. In order to select the synthetic membrane for IVRT, it should also be considered potential interactions between the polymer matrices and the chemical structure of drug molecule as well as formulation components prior to conducting membrane inertness test and IVRT studies.