Multivariate Analysis of a Highly Effective Drug Combination Tablet Containing the Antiepileptic Drug Gabapentin to Enhance Pharmaceutical Properties with a Multicomponent Crystal Strategy

A thorough grasp of the relationship between the crystal structure and properties is necessary for the design of crystals with specific properties using crystal engineering. Gabapentin (GBP), an analogue of the neurotransmitter gamma-aminobutyric acid, is used to treat partial seizures. GBP exhibits a fast dissolution rate. However, because of being plastically and elastically deforming, which increases the possibility of capping or laminating during compression, GBP exhibits poor compaction behavior. The aim of the study was to address the aforementioned issues, involving preparing and characterizing gabapentin monohydrate (GBP·H2O) and cocrystals (GBP-PABA) with p-aminobenzoic acid (PABA). Both the tablets of GBP·H2O and GBP-PABA can successfully slow down the dissolution rate of the original drug and reduce the intrinsic dissolution rate. Additionally, the multicomponent crystals of GBP have slip planes, demonstrating very excellent compaction properties, according to a thorough study on the mechanical properties of crystals. In terms of single-crystal structure and intermolecular interaction, the compressibility assessment of multicomponent crystals by analysis of relationships between mechanical properties and bulk powder compaction behavior further proved its plastic behavior and appropriateness for direct compression. Therefore, the development of multicomponent crystals will effectively solve the determination of the parent drug itself and become an efficient oral combined formulation.