Formulation, in vitro evaluation and characterization of atorvastatin solid dispersion

Abstract

Purpose: To formulate a polymer-incorporated solid dispersion preparation for enhancing the dissolution and bioavailability of atorvastatin calcium trihydrate (ATV), while maintaining oral compatibility.Method: Four different methods, i.e., physical mixing (PM), fusion (F), solvent evaporation (SE) and kneading (K), as well as three different excipients i.e. croscarmellose sodium (CCS), microcrystalline cellulose (MCC) and lactose (LAC) were used to formulate various drug-carrier combinations.Results: In SE method, the rank order of magnitude of drug release was CCS > LAC > MCC, while in fusion and kneading methods, the rank order of release was MCC > CCS > LAC and MCC > CCS > LAC, respectively. Drug release of atorvastatin was maximum (103 %) in FM2 formulation. However,this formulation was non-compatible based on spectroscopic analysis. In contrast, SC2 formulations at 1:2 ratio were compatible in terms of cumulative drug release (99 %), and based on spectroscopic data, thermal analysis and microscopic evaluation.Conclusion: These results confirm that CCS forms a superior interface with atorvastatin when SE formulation method is used. Thus, solid dispersion is a promising approach for enhancing the oral bioavailability of atorvastatin. Keywords: Atorvastatin, Solid dispersion, Bioavailability, Solvent evaporation