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

牙周袋中颗粒剂型的生物相关溶出方法

• 批准号: 9352618
• 负责人: Lisa Cencia Rohan
• 金额: $ 4.97万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352618
• 关键词: Biorelevant; Dissolution; Methods; Particulate; Dosage

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.

溶出度测试是任何药品开发计划的关键组成部分。它在体外提供 用于质量控制评估以及预测体内药物释放的释放数据。体外释放 FDA建议进行试验，以证明受试制剂和参比制剂之间的生物等效性 在大多数仿制药的批准产品。到目前为止，还没有公认的标准或药典 经验证的方法，用于测试药物从缓释牙周产品中释放， 牙周袋的生理方面。这项提案的目标是设计一种生物学上的 用于表征长效制剂药物释放曲线的相关溶出度测试方法 牙周药物产品。此外，在本项目范围内， 将开发模拟牙周袋环境中的生理条件（pH， 渗透压/离子强度、粘度和酶、盐和蛋白质的存在）。为了测试和 验证开发的低容量溶出系统，市售的米诺环素释放PLGA微球 产品，Arestin®，其被放置在牙周袋中以治疗牙周疾病，将被用作 参考产品。将在本研究中开发并评价对照品米诺环素微粒产品。 设计的溶解系统。为了进一步确定本方法的重现性、稳健性和局限性， 开发的系统，涵盖各种生产条件和辅料的产品面板 将配制修饰物并评估体外药物释放。这样，发达国家的能力 区分可能影响产品生物等效性的微小产品差异的方法， 演示。最终，该项目将导致体外溶出度的开发和验证 可以区分不同牙周剂型药物释放曲线的系统， 获取基础数据，以了解制剂放行特性。 该项目将提供有意义的体外测试方法，准确反映和预测 可用于促进牙周仿制药适当评估的生物制剂 产品.作为最终的系统验证，将应用数据驱动的预测建模， 通过表征体外溶出结果如何取决于特定方法特征和配方来获得价值 特性.