Crystal engineering to improve physicochemical properties of mefloquine hydrochloride

Abstract

Background: Pharmaceutical cocrystallization is a promising alternative for improving the solubility and dissolution rate or manipulating other physical properties of active pharmaceutical ingredients. The objective of this investigation was to study the effect of cocrystallization with different cocrystal formers on physicochemical properties of mefloquine hydrochloride. Method: Cocrystals were prepared by solution crystallization method – mefloquine hydrochloride (414.8 mg, 1 mmol) and different cocrystal formers (1/2 mmol) were dissolved in 20 mL of ethanol with warming. Solution was cooled in ice bath for 6 hours. The crystals were isolated by filtration through a membrane (0.45 μm) and dried in the air. The pure drug and the prepared cocrystals were characterized in terms of saturation solubility, drug content, infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, in vitro dissolution studies, and stability studies. Results: The cocrystals showed enhanced solubility and dissolution rate. The cocrystals were found to be stable over the period of 6 months confirmed from stability studies. Conclusion: Cocrystals resist the conversion of anhydrous form of drug into its hydrate which is responsible for the drugs less solubility and dissolution rate.

Keywords:

• Cocrystals
• dissolution
• slurry crystallization
• solubility
• stability

Acknowledgments

Authors are thankful to Shivaji University, Kolhapur, Maharashtra, India, for providing P-XRD analysis and SEM analysis, and Govt. College of Pharmacy, Aurangabad, Saswad College of Pharmacy for their help in the DSC and FTIR analysis, respectively. Authors are thankful to the Principal Prof. Dr. S.B. Bhise, Govt. College of Pharmacy, Karad, Maharashtra, India for providing laboratory facilities.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.