Development of optimal in vitro release and permeation testing method for rectal suppositories

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Rectal Administration

Background:

• Currently, no compendial assays exist for testing drug release from rectal suppositories.
• Establishing reliable in vitro methods is essential for predicting in vivo performance and ensuring bioequivalence.
• Mesalamine suppositories are widely used, necessitating robust quality control measures.

Purpose of the Study:

• To evaluate and identify suitable in vitro release testing (IVRT) and in vitro permeation testing (IVPT) methods for rectal suppositories.
• To assess the in vitro bioequivalence of different mesalamine suppository formulations.
• To investigate the influence of mucin on drug release and permeation, and to explore drug-mucin interactions.

Main Methods:

• Characterization of mesalamine suppositories (weight variation, content uniformity, hardness, melting time, pH, viscoelasticity).
• Evaluation of four IVRT methods (Dialysis, Horizontal Ussing Chamber, Vertical Franz cell, USP apparatus 4) and two IVPT methods (Horizontal Ussing Chamber, Vertical Franz cell).
• Inclusion of molecular docking studies for drug-mucin interactions and use of porcine rectal mucosa for IVPT.

Main Results:

• The USP 4 method was identified as a suitable IVRT technique, and the Horizontal Ussing chamber as a suitable IVPT technique for rectal suppositories.
• In vitro release and permeation profiles of the Reference Listed Drug (RLD) and generic mesalamine suppositories were found to be similar.
• Statistical analysis (Wilcoxon Rank Sum/Mann-Whitney rank test) confirmed the sameness of RLD and generic suppository products based on IVRT data.

Conclusions:

• The USP 4 and Horizontal Ussing chamber methods are recommended for IVRT and IVPT of rectal suppositories, respectively.
• The developed methods successfully demonstrated the in vitro bioequivalence between generic and RLD mesalamine suppositories.
• This study provides a foundation for establishing compendial methods for rectal suppository quality assessment.