Cocrystals of acyclovir with promising physicochemical properties

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Crystallography

Background:

• Acyclovir (ACV) is a vital antiviral medication.
• Improving the physicochemical properties of ACV, such as solubility and dissolution, is crucial for enhanced therapeutic efficacy.
• Cocrystallization is a promising strategy for drug property modification.

Purpose of the Study:

• To investigate the cocrystal forming ability of acyclovir (ACV) with fumaric acid, malonic acid, and DL-tartaric acid.
• To characterize the physicochemical properties and evaluate the stability and dissolution of the novel ACV cocrystals.
• To assess the potential of ACV cocrystals for improved drug delivery.

Main Methods:

• Cocrystallization via grinding with solvent addition and solvent evaporation.
• Characterization using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA).
• Single crystal X-ray diffraction for structural determination of the ACV-fumaric acid cocrystal.
• Evaluation of relative humidity stability and aqueous solubility/dissolution profiles.

Main Results:

• Three novel ACV cocrystals with fumaric acid, malonic acid, and DL-tartaric acid were successfully isolated.
• The crystal structure revealed the formation of a supramolecular synthon in the ACV-fumaric acid cocrystal.
• Cocrystals exhibited significantly enhanced aqueous solubility (up to sixfold for malonic acid cocrystal) and improved dissolution rates compared to parent ACV.
• Malonic acid cocrystals showed approximately double the release rate of hydrated ACV.

Conclusions:

• Cocrystal formation is an effective strategy to enhance the aqueous solubility and dissolution of acyclovir (ACV).
• The characterized ACV cocrystals, particularly with malonic acid, demonstrate potential for improved oral bioavailability and drug delivery.
• Further investigation into these novel cocrystal forms is warranted for clinical development.