Stabilization of Rosuvastatin Calcium Formulation by Prevention of Intermolecular Esterification: An Experimental Design

Abstract

Background: Rosuvastatin calcium is the most effective molecule for the treatment and management of Hypercholesterolemia. This drug easily degrades by exposure to moisture and light and forms unstable formulation by formation of oxidation products, this degradation accelerates in acidic environment of the formulation. The acid form of Rosuvastatin calcium which is the active moiety has a tendency of conversion into lactone form Inactive moiety through “intermolecular esterification” in acidic environment. Synthetic alkalising agents such as tribasic magnesium phosphate is usually added in the tablet formulation to overcome this degradation, but alkalizing agents are harmful to gastric mucosa.Methods: Natural stabilizers such as Xanthan Gum, Chitosan and Guar Gum are used for stabilization. Selection of optimum stabilizer and drug/stabilizer ratio is obtained by quality by design approach by implementing 32 factorial design. Xanthan gum and Chitosan were selected as Critical quality attributes and material attributes with fixed Rosuvastatin Calcium concentration.Results: Tablets consisting of Xanthan Gum and Chitosan in 1:1.4 ratios exhibited maximum stabilization after stability study with 99% assay and dissolution was enhanced by more than 20% i.e. 98% within 30 min as compared to marketed tablets. Statistical test by Analysis of Variance revealed that the model is significant with p value <0.0001 and F-value of 50.58 that the model terms are significant for one factor i.e. the concentration of chitosan as natural stabilizer.Conclusion: The stabilisation of Rosuvastatin calcium was achieved by natural stabilizer i.e. chitosan with QBD approach and the stable tablet formulation was successfully prepared.

Keywords: Rosuvastatin calcium; Quality by Design; Design of Experiment; Natural stabilizers; Chitosan; Xanthan Gum.