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
Highlights
Atorvastatin calcium, a BCS class-II drug, is has low aqueous solubility (< 1 mg/mL) [1]
The standard calibration curve of atorvastatin calcium was prepared in phosphate buffer, pH 6.8 as a dissolution medium, the curve showed almost uniform linearity (Figure not shown)
The absorbance values of the serial dilutions of atorvastatin calcium trihydrate (ATV) used for the standard curve were 0.73, 0.58, 0.43, 0.29, and 0.14 for ATV concentrations of 20, 16, 12, 8 and 4 μg/mL, respectively
Summary
Atorvastatin calcium, a BCS class-II drug, is has low aqueous solubility (< 1 mg/mL) [1]. The low aqueous solubility results in low dissolution and low bioavailability of atorvastatin calcium. Solid dispersion (SD) is a widely recognized approach for increasing solubility drugs that are poorly soluble in aqueous media [4]. Atorvastatin, known as atorvastatin calcium [10], is used for lowering human blood cholesterol levels. It has significant intestinal permeability [1]. Studies have shown that the bioavailability and solubility of crystalline atorvastatin can be enhanced by converting the drug into an amorphous state, and by reducing its particle size [11]
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