The Development of a New Complexation Technique of Hydrocortisone Acetate with 2-Hydroxypropyl-β-Cyclodextrin: Preparation and Characterization

Abstract

In the present study, an inclusion complex composed of hydrocortisone acetate (HA) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) was prepared according phases solubility diagram of Higuchi & Connors and by a method described by Filipović-Grcić J et al..1 with minor modifications to improve the HA water solubility. This new method improved percentage of inclusion reaching the maximum percentage of inclusion (91.52±0.92%) using 5.75mM HA and 135mM HPβCD. This percentage of inclusion was higher than that found by Filipović-Grcić J et al..1 which was 25%. The complex HA/HPβCD was characterized by 1H-NMR through chemical shifts in 1H NMR spectra after the inclusion of HA into the HPβCD cavity, especially H-3, H-5 and H-6 protons was observed to the formation of molecular inclusion complex. Other technique used to characterize the inclusion complex was FT-IR, which showed in the FT-IR spectra of inclusion complex no features bands similar to pure HA molecule; the spectrum is very similar to the HPβCD. The molecular modeling studies results are in agreement with the experimental data that estimates a HA/HPβCD molar ratio of 1:1. The calculated apparent stability constant (KS) was 484 M-1. The results indicate that the HA/HPβCD inclusion complex is more water soluble than HA crystalline powder (pure), the AH solubility was increased on the order of 64 times;