PREPARATION OF ACYCLOVIR-NICOTINAMIDE COCRYSTAL BY SOLVENT EVAPORATION TECHNIQUE WITH VARIATION OF SOLVENT

Abstract

ABSTRACTObjective: This research aims to prepare cocrystal of acyclovir (ACV)-nicotinamide (NCT) by solvent evaporation with a variation of solvent (ethanol,glacial acetic acid, and HCl 0.1 N) to improve the bioavailability of ACV as an antiviral drug.Methods: Cocrystal were developed by solvent evaporation with 1:1 molar fraction, using variation of solvent such as ethanol, glacial acetic acid, andHCl 0.1 N. Further, the prepared ACV-NCT cocrystal were characterized for differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD),Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), and in vitro dissolution.Results: DSC thermogram showed that ACV-NCT cocrystal in ethanol and glacial acetic acid exhibited new endothermic peak at 221.16°C and216.40°C, whereas no peaks were found for HCl 0.1 N. PXRD diffractogram showed that ACV-NCT cocrystal in ethanol exhibited new diffraction peaksat 2θ 5.9°; 9.2°; dan 13.3°, whereas no peaks were found for glacial acetic acid and HCl 0.1 N. FT-IR characterization of ACV-NCT cocrystal in ethanolshowed disappearance of transmission peaks at 3373/cm indicating the loss of NH bands of NCT. Furthermore, C=O of ACV and NCT were observed at1693/cm, and 1666/cm indicated a formation of hydrogen bonding between ACV and NCT. SEM micrographs showed that cocrystals have a differentshape compared to ACV and NCT. DE15 showed that there was a significant increase of ACV-NCT cocrystal dissolution rate in ethanol compared to thephysical mixture and ACV.Conclusion: The study concludes that ACV-NCT cocrystal in ethanol were successfully formed and the dissolution rate of ACV can increase significantly(α=0.05).Keywords: Cocrystallization, Solvent, Acyclovir, Nicotinamide, Solvent evaporation.