title: Cocrystals of acyclovir with promising physicochemical properties.
abstract: Cocrystal forming ability of antiviral drug acyclovir (ACV) with different coformers was studied. Three cocrystals containing ACV with fumaric acid, malonic acid, and DL-tartaric acid were isolated. Methods of cocrystallization included grinding with dropwise solvent addition and solvent evaporation. The cocrystals were characterized by powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. The crystal structure of the cocrystal with fumaric acid as conformer was determined by single crystal X-ray diffraction. Formation of supramolecular synthon was observed in the cocrystal. Stability with respect to relative humidity for the three cocrystals was evaluated. The aqueous solubility of the ACV-cocrystal materials was significantly improved with a maximum of malonic acid cocrystal, which was about six times more soluble at 35°C compared with that of parent ACV. The dissolution profile indicates that at any particular dissolution time, the concentration of cocrystals in the solution was higher than that of the parent ACV, and malonic acid cocrystals had a maximum release of about twice than the hydrated ACV.
authors.affiliation: Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, N6A 5B9, Ontario, Canada.
authors.forename: Anindita
authors.initials: A
authors.lastname: Sarkar
authors.forename: Sohrab
authors.initials: S
authors.lastname: Rohani
mesh_terms: D000212:Acyclovir / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D003460:Crystallization; D018360:Crystallography, X-Ray; D003998:Dicarboxylic Acids / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D005650:Fumarates / Q000737:chemistry; D006860:Hydrogen Bonding; D007700:Kinetics; D008314:Malonates / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D010592:Pharmaceutic Aids / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D013644:Tartrates / Q000737:chemistry; D013818:Thermogravimetry
chemical_list: D000998:Antiviral Agents; D003998:Dicarboxylic Acids; D005650:Fumarates; D008314:Malonates; D010592:Pharmaceutic Aids; D013644:Tartrates; C032005:fumaric acid; C030290:malonic acid; C029768:tartaric acid; D000212:Acyclovir
keywords: co-crystal; crystal engineering; dissolution rate; single crystal; solubility; stability; synthon