A Biorelevant Dissolution Methods for Particulate Dosage Forms in the Periodontal Pocket

溶出度测试是任何药品开发计划中的关键组成部分。它在体外提供了 用于质量控制评估和体内药物释放预测的释放数据。体外释药 FDA建议进行测试，以验证测试和参考之间的生物等效性 产品中批准的仿制药最多。到目前为止，还没有公认的标准或指南 经验证的测试缓释牙周产品药物释放的方法 牙周袋的生理方面。这项提议的目标是设计一种生物学上的 长效释药谱表征的相关溶出度试验方法 牙周药物产品。此外，在本项目的范围内，一种牙周沟液模拟剂 将开发出模拟牙周袋环境中的生理条件(pH， 渗透压/离子强度、粘度以及酶、盐和蛋白质的存在)。为了测试和 市售米诺环素PLGA微球小体积释药系统的验证 放在牙周袋中用于治疗牙周病的产品Arestin®将被用作 参考产品。将在年内开发和评估米诺环素微粒产品的比较器。 设计了溶出系统。进一步确定可重复性、健壮性和局限性 开发的系统，一组跨越各种生产条件和辅料的产品 将制定和评估体外药物释放的改进方案。如此一来，发展起来的能力 区分可能影响产品生物等效性的微小产品差异的方法如下 演示了。最终，该项目将导致体外溶出物的开发和验证 可以区分不同牙周剂型的药物释放曲线的系统 获取基础数据以了解药物产品的释放特性。 该项目将提供有意义的体外测试方法，准确地反映和预测 生物性能，可用于促进非专利牙周药物的适当评估 产品。作为最终的系统验证，将应用数据驱动的预测建模，它提供了一个独特的 通过表征体外溶出结果如何依赖于特定的方法特征和配方来确定其价值 属性。

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.