Effect of Grinding on the Solid-State Stability and Particle Dissolution of Acyclovir Polymorphs

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry

Background:

• Acyclovir is an important antiviral medication.
• Understanding the solid-state properties of acyclovir polymorphs is crucial for drug formulation.
• Polymorphism can significantly impact drug efficacy and bioavailability.

Purpose of the Study:

• To investigate the solid-state transformations of four acyclovir polymorphs under different grinding conditions.
• To evaluate the impact of grinding methods on particle size, shape, and water content.
• To identify stable polymorphs with improved dissolution rates.

Main Methods:

• Solid-state characterization of four acyclovir polymorphs.
• Grinding experiments at room temperature (Method A) and cryo-grinding with liquid nitrogen (Method B).
• Analysis using X-ray powder diffractometry, scanning electron microscopy, and thermal analysis.

Main Results:

• Anhydrous Form I and hydrate Form VI were stable under both grinding methods.
• Anhydrous Form II converted to hydrate Form V under cryo-grinding.
• Hydrate Form V transformed to anhydrous Form I and then hydrate Form VI under room temperature grinding.
• Forms I and VI showed significant particle size reduction and enhanced dissolution rates.
• Cryo-grinding of Form I resulted in the highest dissolution rate.

Conclusions:

• Acyclovir Forms I and VI exhibit desirable physicochemical stability and particle size reduction upon grinding.
• These stable forms demonstrate potential for improved dissolution and bioavailability.
• Cryo-grinding of acyclovir Form I offers the most promising approach for enhancing dissolution rates.