Predominantly Amorphous Atorvastatin Calcium–Nicotinamide Solid: Solid-State Characterisation and Dissolution Enhancement

Abstract

Atorvastatin calcium is a poorly water-soluble drug whose oral performance is limited by low aqueous solubility and slow dissolution. This study prepared an atorvastatin calcium–nicotinamide multicomponent solid by solvent evaporation and classified its solid-state form using integrated physicochemical characterisation. Atorvastatin calcium and nicotinamide were processed at a 1:1 molar ratio using an ethanol–acetone solvent system. The parent compounds, physical mixture, and solvent-evaporated solid were evaluated using powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and scanning electron microscopy. Aqueous solubility and dissolution performance were also assessed. The processed atorvastatin calcium–nicotinamide solid showed a broad diffuse halo with marked attenuation of the characteristic crystalline peaks of both parent compounds, supporting reduced long-range crystallographic order rather than formation of a well-defined crystalline cocrystal. Spectral changes in the O–H/N–H and carbonyl/amide regions supported intermolecular interaction, while thermal and morphological analyses further indicated solid-state transformation. The transformed solid increased aqueous solubility from 1.41 ± 0.02 to 5.61 ± 0.04 mg/mL and produced faster dissolution than crystalline atorvastatin calcium in both 0.1 N HCl and phosphate buffer media. Overall, the data support formation of a predominantly amorphous or co-amorphous atorvastatin calcium–nicotinamide multicomponent solid with possible residual crystallinity. The improved apparent solubility and dissolution are plausibly associated with reduced crystallinity and atorvastatin calcium–nicotinamide intermolecular interaction.