Investigation of the compatibility between kaempferol and excipients by thermal, spectroscopic and chemometric methods

Abstract

Compatibility is an important step in pre-formulation studies during the development of solid dosage forms. In the present study, we used thermal analysis (differential scanning calorimetry and thermogravimetry), isothermal stress testing followed by high-performance liquid chromatography and Fourier transform infrared spectroscopy complemented by two multivariate techniques (hierarchical cluster analysis and principal component analysis) to detect potential incompatibilities between kaempferol and commonly used solid dosage form excipients in binary mixtures. The excipients that were studied were starch, microcrystalline cellulose, magnesium stearate, hydroxypropylmethylcellulose, lactose, sodium lauryl sulfate and polyvinylpyrrolidone. The thermal analyses results indicated interactions occurred between kaempferol and all excipients studied except microcrystalline cellulose. However, infrared spectroscopy complemented by multivariate analysis indicated compatibility between kaempferol and all excipients. Isothermal stress testing confirmed the absence of significant change in the content of kaempferol in the binary mixtures. Our study demonstrates the importance of combining different techniques and multivariate data analysis for pre-formulation drug-excipient analysis.