Dissolution methods are commonly used to identify differences in the physicochemical properties among drug products caused by manufacturing differences. These drug release studies are commonly employed to assess performance characteristics of complex dosage forms and serve as a standard method for manufacturing quality control. Besides quality control, dissolution studies are also used to support bioequivalence of generic products in the generic drug approval process. Currently, a reliable dissolution test method for long acting periodontal drug products is not available. The objectives of the present project are to develop and evaluate a bio-relevant dissolution method for long-acting periodontal drug products and demonstrate its ability to distinguish performance differences of these drug products. To achieve these goals, this project will first use computer model simulations to evaluate the drug concentration profile in the periodontal pocket as a function of the flow dynamics of gingival crevicular fluid and drug physicochemical properties (its permeability across gingiva). This evaluation will identify the limitations of a flow-through dissolution system for bio-relevant dissolution testing of the drug products and provide spatial error analyses such as the impacts of dissolution chamber dimensions and drug product locations in the chamber on drug dissolution before the construction of the dissolution apparatus. Dissolution apparatus prototypes will then be constructed using three-dimensional (3D) printing for testing. A simulated gingival crevicular fluid as dissolution medium will be developed. Studies will be performed to understand the effects of different conditions such as dissolution medium flow rate on drug dissolution. These studies will be carried out with the assistance of the knowledge obtained from the computer modelling, and the dissolution results will be compared with those from the modelling. Q1/Q2 equivalent test products of a long-acting periodontal reference listed drug (RLD) product (PerioChip) and test products that have Q1 and Q2 differences will be manufactured. The performance of the dissolution test method will be evaluated using these Q1/Q2 equivalent test formulations and test formulations of Q1 and Q2 differences. The attributes that affect drug dissolution behavior will also be identified. It is hypothesized that this new dissolution test method will provide scientifically-based information to help FDA in the examination of bioequivalence and the evaluation of generic long-acting periodontal drug products.
Long-acting periodontal drug products include biodegradable microspheres, gels, implants, and tablets. A robust and bio-relevant in vitro drug release assay for these dosage forms is currently not available. The objective of this project is to develop a bio-relevant dissolution method for long-acting periodontal dosage forms. The properties that affect the drug dissolution behavior of periodontal dosage forms will also be identified. Such information will assist FDA to develop recommendations for bioequivalence of generic long- acting periodontal drug products.
