Controlled Crystallization of Acetazolamide from Aqueous Polymeric Solutions for Enhancing Dissolution Rate: Application of Statistical Moment Theory and Molecular Docking

Abstract

Presence of additives in crystallization process in a controlled manner can lead to different crystal morphologies which could have a favourable impact on drug dissolution rate. Four different hydrophilic polymers (methylcellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, and carboxymethyl cellulose) were used for the controlled crystallization of acetazolamide (ACZ) by solvent evaporation technique. Crystal imperfections of ACZ occurred in the lattice of growing crystal when crystallized from aqueous polymeric solution and evaluated using both the traditional Full Width at Half Maximum (FWHM) (b) and statistical mean value of the XRD peak width (b¢). Crystal imperfection has brought about significant improvement in the dissolution of newly produced acetazolamide crystals. ACZ crystal produced in presence of Hydroxypropyl methylcellulose (AHPMC) showed crystal imperfection to the maximum extent and also the greatest dissolution of the drug was noticed from AHPMC compared to other crystals. Statistical mean value of the peak width of XRD data as the error-free technique has been utilized successfully for estimating crystallite properties of acetazolamide crystallized from ethanol as solvent and aqueous polymeric solution as anti-solvent. Crystallite properties using traditional Full Width Half Maxima method and the error-free Statistical Moment Analysis were compared. This controlled crystallization technique could be utilized in the design and development of formulation for improved solubility and bioavailability of the drug.