Modification of small dissolution chamber system for long-acting periodontal drug product evaluation

Abstract

Conventional dissolution testing methods may not be suitable for long-acting periodontal drug products due to the small volume, slow fluid flow rate, and environment in the periodontal pocket. The objective of this study was to evaluate a 3D-printed small volume flow-through dissolution chamber system (modified from a previous study) for biorelevant and dose-discriminating testing. Three periodontal drug products with different dosage forms were tested: Atridox, Arestin, and PerioChip. Modifications were made to suit the specific characteristics of these dosage forms. No significant differences were observed between the % drug release profiles in vitro and in vivo except for Atridox. The differences observed with Atridox could be related to the exposing surface area of the drug product. Similar differences were observed from this effect in COMSOL model simulations. Overall, the drugs show reasonable in vitro-in vivo correlations (R² ≥ 0.91) with linear regression slopes close to unity. For dose discrimination between 75% and full dosing, significant differences were observed in the drug release data at specific time points of the products (p ≤ 0.05). The present results suggest that a small volume dissolution chamber with slow flow rate could potentially provide biologically relevant and dose-discriminating evaluations for periodontal drug products.

Keywords: Dissolution; Drug Release; In vitro-in vivo correlation (IVIVC); Periodontal.