An Integration of Absorption Chamber with USP II Dissolution Appara

Dr Konstantin Tsinman, R&D, pion-inc, Billerica, USA

INTRODUCTION - Traditional (USP) dissolution tests have been used in the pharmaceutical industry to perform quality control of manufacturing process for drug products, and also to compare performance of different drug product formulations during the late stage of the drug development process. It has been a subject of multiple debates if differences in the dissolution profile would be biorelevant, i.e. would lead to the significant changes in the in vivo absorption properties of active pharmaceutical ingredients (API). The goal of this study was to develop a method enabling simultaneous monitoring of dissolution of the drug product in the compendial apparatus at the same time providing the means to assess kinetic of API penetration into the absorption chamber separated from the dissolution vessel by a lipophilic membrane.

MATERIALS AND METHODS - Naproxen (NPX, Figure 1) was selected as a model compound for this “proof of concept” study. Over the counter Brand Name NPX sodium 220 mg dose liquid gel capsules (Alive® Liquid Gels, Bayer) and the Generic NPX sodium caplets (the same dose, generic supermarket brand) were used in the study as model drug products (Figure 2). Concentration monitoring in both dissolution and absorption chambers was enabled through fiber optic UV probes connected to the Rainbow Dynamic Dissolution Monitor instrument (Pion Inc).

RESULTS AND DISCUSSION -The experiment began in 800 mL at pH 1.6 simulating gastric conditions and then after 30 min media in the dissolution vessel was converted to FaSSIF by adding 200 mL of specially formulated concentrate. Figures 4 and 5 show dissolution and appearance profiles of NPX studied with Flux apparatus.

Brand Name and Generic NPX products have very different release profiles (Figure 6) one being consistent with extended release (Brand Name) and the other with immediate release profiles.