Development and validation of an in vitro release test (IVRT) method for a locally acting mesalamine suppository.

Rectal suppositories are a common FDA-approved dosage form that are administered via the rectal route. Currently, there is limited information in the literature related to in vitrorelease test (IVRT) methods for rectal suppositories that may be utilized to support a demonstration of bioequivalence (BE).To facilitate a comparison of in vitrorelease rates between a reference listed drug (RLD) product and a prospective generic suppository product as a component of a BE approach, it is essential to develop a reproducible and discriminatory IVRT method. Mesalamine rectal suppository, 1 gm, was selected as the model drug product in the present research. Three different IVRT methods were investigated, using a vertical diffusion cell (VDC), or USP apparatus 2 and 4 with adapters. Laboratory-made suppositories with different strengths, all prepared using a melt-fusion method, were used in the IVRT method development and validation. The VDC method demonstrated better reproducibility compared to other IVRT methods studied and was further qualified and validated. The in vitro release rate of mesalamine rectal suppositories obtained using the VDC method showed good Higuchi model fitting with the r2 of each individual cell greater than 0.97. Moreover, the developed VDC method was reproducible and sensitive in evaluating the in vitrorelease rates of mesalamine rectal suppositories. These data suggest that an IVRT method utilizing a VDC may be used to develop and validate a sensitive and discriminatory method that could ultimately be used to compare release rates between a prospective generic mesalamine suppository and the corresponding RLD as part of a characterization-based BE approach.