Formulation and Evaluation of Hard Gelatine Capsules of Atorvastatin Prepared by Kneading for Enhancement of Oral Bioavailability

Abstract

Atorvastatin calcium, a widely prescribed HMG-CoA reductase inhibitor used in the management of hypercholesterolemia and dyslipidaemia, belongs to BCS Class II, characterized by low aqueous solubility and consequently poor and variable oral bioavailability (approximately 12–14%). This limitation arises primarily from poor dissolution in the gastrointestinal fluid and extensive first-pass hepatic metabolism. The present work was undertaken to enhance the solubility, dissolution rate, and hence the oral bioavailability of Atorvastatin by preparing an inclusion complex with a hydrophilic carrier (β-cyclodextrin) using the kneading method, followed by formulation into hard gelatine capsules. Complexes were prepared at different drug-to-carrier molar ratios. and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD) to confirm complexation. Micromeritic properties of the optimized complex were evaluated before capsule filling. The prepared capsules were evaluated for weight variation, disintegration time, drug content uniformity, and in-vitro dissolution studies.   Results indicated a significant improvement in aqueous solubility and dissolution rate of the kneaded complex compared to pure drug, with the 1 :4 (drug: carrier) ratio showing the most  favourable results, releasing over 95% of the drug within 45 minutes compared to less than 40% for pure Atorvastatin.  The study concludes that the kneading technique is a simple, cost-effective, and scalable approach for enhancing the dissolution and potential oral bioavailability of poorly water-soluble drugs like Atorvastatin.