Novel Co-processing Methodology To Enable Direct Compression of a Poorly Compressible, Highly Water-Soluble Active Pharmaceutical Ingredient for Controlled Release

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.