Solubility and Dissolution Enhancement of BCS Class-IV Anti-Diabetic Drug Tolbutamide by Solid Dispersion Technique
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Abstract
Even though the oral route of drug administration is typically considered the simplest and easiest technique in clinical applications, the solubility and dissolution of various medications play a major restriction in the process. Solid dispersion by kneading has long been recognised as one of the most promising strategies for improving the solubility of drugs that are poorly soluble. The reason tolbutamide, a new anti-diabetic medication, was selected for this investigation was because of its poor permeability and restricted solubility, which required the creation of a solid dispersion in order to increase its bioavailability. One major obstacle is the drug's limited water solubility, which means that higher doses are needed, which limits its potential for clinical application. To make the solid dispersion, hydrophilic polymers in the ratios of1:1,1:3, and 1:5 were kneaded along with beta cyclodextrin and PEG 4000. In terms of zeta potential, the resulting particles ranged from -58 mV to -17 mV, with a nanometer size dispersion of 240 to 640 nm. Maximum in vitro drug dissolution (determined using the standard USP type II paddle procedure with the sample immersed in a dialysis bag) was seen for a formulation with a drug:beta cyclodextrin ratio of 1:1. When compared to a pure drug suspension (about 10% release), the formulation showed a solubility improvement of roughly 7.5 times. The stability, drug-carrier compatibility, crystalline-to-amorphous transition, and uniform spherical particle production were verified using additional characterisation techniques such as scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The solid dispersion method improved CGF solubility and dissolution in all tested situations.