Dissolution testing is a key component in any pharmaceutical product development program. It provides in vitro release data for use in quality control assessment as well as prediction of in vivo drug release. In vitro release testing is recommended by the FDA for the demonstration of bioequivalence between test and reference products in the approval of most generic drugs. To date, there is no recognized standard or compendial validated methods for testing drug release from extended release periodontal products which accounts for the physiological aspects of the periodontal pocket. The goal of this proposal is to design a biologically relevant dissolution testing method for characterization of drug release profile for long-acting periodontal drug products. Additionally, within the scope of this project, a gingival crevicular fluid simulant will be developed which mimics the physiological conditions in the periodontal pocket environment (pH, osmolality/ionic strength, viscosity, and the presence of enzymes, salts and proteins). In order to test and validate the developed low volume dissolution system, the marketed minocycline releasing PLGA microsphere product, Arestin, which is placed in the periodontal pocket to treat periodontal disease will be utilized as the reference product. A comparator minocycline microparticle product will be developed and evaluated in the designed dissolution system. Further to establish the reproducibility, robustness and limitations of the developed system, a panel of products which span various manufacturing conditions and excipient modifications will be formulated and assessed for in vitro drug release. This way, the capacity of the developed methods to differentiate small product differences which may impact product bioequivalence will be demonstrated. Ultimately this project will lead to development and validation of an in vitro dissolution system that can discriminate drug release profile of different periodontal dosage forms allowing for acquisition of fundamental data toward the understanding of drug product release characteristics. This project will provide meaningful in vitro test methods that accurately reflect and predict bioperformance which can be applied to facilitate appropriate assessment of generic periodontal drug products. As a final system validation, data-driven predictive modeling will be applied which offers a unique value by characterizing how in vitro dissolution results depend on specific method features and formulation properties.
Currently there is no available standard dissolution system which can be applied to ?prove? bioequivalence for long acting periodontal drug products. Dissolution testing is a key component in any pharmaceutical product development program. It provides data which describes how reproducibly drug is released from a product and can be used to predict drug release in the body. The goal of this proposal is to design a dissolution testing method which mimics the environment in periodontal pocket of the human body. This method can become a standard method used to test bioequivalence for generic products intended to treat periodontal disease.
