Investigation on Complexation Efficiency of Hp-β-Cd/ Nifedipine Complex: pH Effect

Abstract

Inclusion complex can enhance the drug solubility, stability, and masking smell. Cyclodextrin (CD) is a commonly used host molecule for inclusion, with three main types of CD, exist, α, β, and γ. They are classified based on their chemical structure. The derivative of β-CD, (Hydroxypropyl-βCyclodextrin; HP-β-CD), is widely used in pharmaceutical formulations. HP-β-CD works by a dynamic equilibrium process for inclusion. Nifedipine is a Class II drug (Biopharmaceutical Classification System) that has poor solubility in water, and high permeability through the cellular membrane. The Phase-solubility profile of nifedipine/HP-β-CD complex showed an AL type (according to Higuchi and Connors' method) indicating a complex ratio of 1:1. The objective of this study was to investigate the pH effect on the inclusion process of nifedipine/HP-β-CD. The results of this study showed that ionization pH conditions improved nifedipine solubility in water to a limited extent however it was not as efficient as the unionization pH conditions since unionization conditions produced higher Complexation Efficiency (CE) and the stability constant (K1:1) value. Therefore, maintaining the drug in a unionized form is perhaps a more efficient way of producing inclusion complex with HP-β-CD. In order to characterize the inclusion complex thus formed between the drug and HP-β-CD, a solvent evaporation method was used to prepare the complex which was compared to a physical mixture, pure drug, and pure HP-β-CD. Significant differences were found to exist between the inclusion complex and all the other groups based on the TGADSC, ATR, and PXRD analysis.