Electronic Theses and Dissertations

Date of Award

1-1-2023

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

First Advisor

Michael A. Repka

Second Advisor

Walter Chambliss

Third Advisor

Seongbong Jo

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

The present study is intended to increase the solubility and dissolution rate of Atorvastatin calcium (ATN Ca) by formulating the drug- hydroxy-propyl-beta cyclodextrin (HPBCD) complexes using solvent-assisted extrusion (SAE) using a twin-screw extruder. Various studies on ATN Ca saturation solubility in water and other pH mediums revealed a pH-dependent solubility with a difference. Thus, the saturation solubility for ATN Ca and Solvent Assisted Extruded complex was conducted in water and different pH mediums in this study. Phase solubility studies between ATN Ca and CDs revealed an AL-type solubility profile exhibiting a linear increase with HPBCD. Drug-HPBCD complexes were made using the solvent-assisted extrusion (Twin Screw Extruder) procedure and conventional techniques, including physical mixing and the kneading method. The solubility of the SAE complexes, as compared to normal ATN Ca (0.0167 mg/mL), was 0.294 mg/mL, respectively. Differential scanning calorimetry and Fourier transform infrared spectroscopy analyses were used to confirm the formation of drug-cyclodextrin inclusion complexes. The formulated products were filled into #2 clear gelatin capsules for better dissolution. According to tests on drug release at 5 min, 10 min, 15 min, and 30 min time intervals, ATN Ca was released at the highest rate from solvent-assisted extruded complex (103 %) compared to other samples. When compared to the drug release from complexes formed by kneading was much lower (89 %). All these studies show promising results to conclude that the complex formed through solvent-assisted extrusion (SAE) has enhanced the solubility and dissolution rate of the Atorvastatin Calcium.

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