Determination of pH-Solubility Profile and Development of Prediction Models for pH-Dependent Solubility of Atorvastatin Calcium

Abstract

Background: Aqueous solubility is a key parameter in understanding drug transport in the body and also in the development of analytical methods. Determination of a complete pH-solubility profile is essential during the pre-formulation stage, and it is also required to define the class of drug according to the biopharmaceutical classification system. Objectives: This study aimed to generate solubility data to obtain a complete pH-solubility profile for Atorvastatin calcium using the spectrophotometric method and to develop models for the prediction of aqueous solubility of Atorvastatin calcium at a given combination of the pH and temperature. Methods: The developed pH independent spectrophotometric method was applied to determine the pH solubility profile of the drug at three different temperatures. Models for the prediction of solubility were generated by using a full factorial design and validated by determining solubility experimentally at some combinations of pH and temperature within the design spaces. Results: Solubility of Atorvastatin calcium was found to increase gradually with pH within a range of pH 1.2-4.0 and pH 9.0-12.0 while increasing drastically with pH within a range of pH 4.0-9.0 at all three temperatures. Experimental values of solubility of Atorvastatin calcium were found to be in good agreement with predicted values from models. Conclusion: Predictive models generated from the experimental values are good indicative of the solubility of Atorvastatin calcium with respect to temperature and pH of the medium and can be used for accurate prediction of aqueous solubility within the design space of the models.