Coprocessing involves integration of multiple substances to improve the physical, chemical, mechanical, and biopharmaceutical properties of a material. Coprocessing is a promising technique in the pharmaceutical industry which support both drug substance and drug product processes. When active pharmaceutical ingredients (APIs) are coprocessed with excipients, it can enable direct compression and continuous manufacturing. Hydroxypropyl cellulose (HPC-L), a commonly used excipient in pharmaceutical formulations, can enhance drug stability, solubility, and bioavailability. In this study, we have employed coprecipitation (CPT) to coprocess metformin hydrochloride (MET) with HPC-L, resulting in the formation of agglomerates with improved physical attributes without any risk of polymorphic changes. Acetone/acetonitrile and heptane were used as solvent and antisolvent, respectively. Screening study revealed that the use of a rotor stator helps to control the size of metformin hydrochloride and HPC-L agglomerates (M-CPT) without negatively impacting bulk density and powder flow properties. The CPT agglomerates showed residual solvent levels within the specified ICH limits. Powder rheology results demonstrated a sixfold increase in FFC of M-CPT compared to neat MET. The compressibility, tabletability, compactability, and “In-Die” Heckel analysis data further suggested that the M-CPT agglomerates are directly compressible with no observable changes in the dissolution profile of MET. Overall, this study demonstrates application of CPT approach to tune the physical and mechanical properties, and HPC-L can be used as an excipient of choice for CPT technique to improve the compressibility and flowability of APIs.

中文翻译：

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通过共沉淀 (CPT) 与羟丙基纤维素 (HPC-L) 共处理，增强难压缩性盐酸二甲双胍的材料属性

协同处理涉及多种物质的整合，以改善材料的物理、化学、机械和生物制药特性。协同处理是制药行业一项有前途的技术，它支持原料药和药品加工。当活性药物成分（API）与赋形剂共同加工时，可以实现直接压片和连续生产。羟丙基纤维素（HPC-L）是药物制剂中常用的赋形剂，可以增强药物的稳定性、溶解度和生物利用度。在本研究中，我们采用共沉淀 (CPT) 方法共处理盐酸二甲双胍 (MET) 与 HPC-L，从而形成具有改善的物理属性的附聚物，且没有任何多晶型变化的风险。丙酮/乙腈和庚烷分别用作溶剂和反溶剂。筛选研究表明，使用转子定子有助于控制盐酸二甲双胍和 HPC-L 附聚物 (M-CPT) 的尺寸，而不会对堆积密度和粉末流动特性产生负面影响。CPT 附聚物显示残留溶剂水平在指定的 ICH 限值内。粉末流变学结果表明，与纯 MET 相比，M-CPT 的 FFC 增加了六倍。可压缩性、可压片性、可压实性和“模内”Heckel 分析数据进一步表明，M-CPT 附聚物可直接压缩，MET 溶出曲线没有可观察到的变化。总体而言，本研究证明了应用 CPT 方法来调整物理和机械性能，并且 HPC-L 可以作为 CPT 技术的辅料选择，以提高 API 的可压缩性和流动性。