Development of Fast Release Aminated Tamarind Gum Carrier-based Solid Dispersion containing Tablets of Ketoconazole for Solubility and Dissolution Rate Enhancement

Abstract

This work enhances the solubility as well as dissolution of the biopharmaceutical classification system (BCS) II drug ketoconazole (KTZ) using fast-dissolving tablets that contain solid aminated tamarind gum (ATG). In the first stage amination of the tamarind gum was done to form ATG and which was confirmed by the presence of characteristic peaks using Fourier-transform infrared spectroscopy (FTIR). DSC-TGA analysis showed a weight loss with 3.91% at 100℃, 54.42% loss at 235 to 425℃ and 90% at 485℃. The proton nuclear magnetic resonance (1H-NMR) showed all resonance peaks observed in ATG. The XRD analysis of ATG confirmed the amorphous nature of the material. The second phase involved developing KTZ-loaded solid dispersion (SD) using the kneading process. KTZ SD showed drug content of 94.55 to 97.21%. SD of KTZ manufactured with TG showed 2.55 to 23.82-fold solubility enhancement in water while in case of SD with ATG showed 28.51 to 33.19-fold solubility enhancement. KTZ had a 32% dissolution rate in the pure drug sample, but the SD5 formulation showed a complete release of solid dispersion in 120 minutes. In FTIR, the disappearance of the peak signifies the production of solid dispersion and the drug’s transformation from a crystalline to an amorphous state. Powder X-ray diffraction (PXRD) analysis of solid dispersions reveals a notable decline in crystallinity, as shown by the removal of strong, distinguishing peaks. The scanning electron microscope (SEM) analysis confirmed the successful development of the SD in which KTZ was observed to be dispersed in a polymeric carrier. Optimized KTZ-loaded SD were utilized in fast-dissolving tablets as the third phase. When compared to the drug release achieved from solid dispersions, it was discovered that the dissolving characteristics of all formulation batches were improved.