Abstract:

The objective of the present work was to prepare cocrystals of poorly soluble drug Atorvastatin Calcium (AVA) with the aim of increasing its solubility and dissolution properties. Screening of 8 cocrystal formers (CCFs) was performed by Hansen solubility parameter (HSPs) using 4 methods- neat grinding, solvent drop grinding, solvent evaporation and sonocrystallization in equimolar ratio. Solubility of AVA cocrystal (1.9 fold increase) in comparison to plain AVA drug has been demonstrated with solubility experiments. FTIR spectra of AVA cocrystal showed disappearance of O-H group indicating the formation of hydrogen bond synthon between the drug and CCFs. DSC thermogram showed drastic reduction in melting point from 164.6°C to 71.9 °C indicating the reduction in cohesive energy and increase in solubility. XRD pattern showed new crystalline peaks at 2θ values of 9.858°, 15.201°, 22.907°, 25.407°, 29.496°. SEM analysis showed changes in the morphological characteristics as compared to drug and CCFs, indicating different crystalline nature. Experimental design was applied to optimize AVA cocrystal IR tablet for concentration of aerosil (X1) and MMC 102 (X2) and were evaluated for drug release (Y1) and friability (Y2). It was found that as the concentration of aerosil and MMC 102 increased friability decreased and %drug release increased. A drug release of 98.54±1.163% and friability of 0.515±0.090 % was obtained for optimized batch. Ex vivo diffusion study was carried out by isolating rat stomach tissue, exhibiting higher drug release (95.71±0.98 %) than plain AVA and marketed tablet. Thus formulating AVA cocrystal and its subsequent formulation in optimized IR tablet gives a promising opportunity for manufacturing a drug with increased bioavailability.

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