Herein we introduce an innovative process for the preparation of a directly compressible active pharmaceutical ingredient (API) and excipient agglomerates for an extended-release formulation of a highly water soluble drug, demonstrated with metformin HCl. Metformin is poorly compressible and currently employs wet granulation for tablet manufacturing, resulting in long cycle times. We have co-processed metformin HCl with hydroxypropyl methylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) in a solvent medium to generate agglomerates that were tableted via direct compression, thereby reducing the drug product manufacturing cycle time and cost while maintaining the extended-release dissolution profile. The intimate mixing of HPMC and NaCMC with metformin HCl through co-processing reduces the risk of segregation during downstream handling and tableting. Additionally, this process reduced the excipient load required to achieve the target dissolution profile and bioequivalence, leading to reduced tablet mass and size with a 1000 mg drug load.

中文翻译：

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新型协同处理方法，可直接压缩可压缩性差，高度水溶性的活性药物成分进行控释

本文中，我们介绍了一种创新方法，用于制备可直接压缩的活性药物成分（API）和赋形剂附聚物，用于高水溶性药物的缓释制剂，并用盐酸二甲双胍证明。二甲双胍的可压缩性差，目前将湿法制粒用于片剂生产，从而导致较长的循环时间。我们在溶剂介质中将盐酸二甲双胍与羟丙基甲基纤维素（HPMC）和羧甲基纤维素钠（NaCMC）进行了共处理，以生成通过直接压片压片的附聚物，从而减少了药品生产周期和成本，同时保持了延长释放的溶出度轮廓。通过共处理将HPMC和NaCMC与盐酸二甲双胍紧密混合，可降低下游处理和压片过程中分离的风险。此外，该过程减少了达到目标溶出曲线和生物等效性所需的赋形剂载量，从而在1000毫克载药量下降低了片剂的质量和大小。