Co-crystallization of Amoxicillin Trihydrate and Potassium Clavulanate Provides a Promising Approach for Preparation of Sustained-Release Microspheres.

Abstract

This work aimed to prepare sustained-release microspheres for amoxicillin trihydrate and potassium clavulanate. Co-crystals of amoxicillin trihydrate and potassium clavulanate were prepared using three different techniques, including supercritical fluid technology. Full characterization was performed for the prepared co-crystals, including molecular dynamic simulation. Next, the co-crystals were microencapsulated with ethylcellulose using the emulsion solvent evaporation method in spherical microspheres. Physicochemical characterizations for the prepared co-crystal were performed using FTIR, DSC, and PXRD. Finally, scanning electron microscopy was used to assess the morphology of the prepared microspheres. Physicochemical studies showed the solid-state interaction between amoxicillin trihydrate and potassium clavulanate in the prepared co-crystals. The total energy suggested differences between the three methods of co-crystal preparations suggesting some structural changes have occurred with better stabilization at supercritical fluid technology. Encapsulation of the co-crystals was successfully performed using ethylcellulose polymer. The in vitro release studies revealed sustained-release profiles for the co-crystal microspheres. Potassium clavulanate was released at a lower rate from the crystal microspheres prepared using co-crystals than the release in microspheres of potassium clavulanate alone. The empirical Higuchi model best fitted the in vitro release profile for amoxicillin trihydrate-potassium clavulanate co-crystal microspheres.