Electronic Theses and Dissertations

Date of Award

1-1-2018

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

Department

Pharmaceutics and Drug Delivery

First Advisor

Michael A. Repka

Second Advisor

S. Narasimha Murthy

Third Advisor

Chalet Tan

Relational Format

dissertation/thesis

Abstract

Purpose: The objective of the present study was to develop lipid-based gastro-retentive floating drug delivery system of amorphous Cefuroxime Axetil (CA) to minimize the enzymatic degradation in the gastro intestinal tract utilizing hot-melt extrusion technology for improved absorption.

Methods: Preliminary studies were performed to select the appropriate lipids. Selected ratios of CA and lipids were extruded using a twin screw hot-melt extruder. Extrudates obtained were milled to obtain floating granules and were further evaluated for drug content, floating strength and micromeritic properties. In vitro drug release studies were performed in 900 mL of simulated gastric fluid (without enzyme) of pH 1.2. The formulations were also studied for their polymorphic nature. Differential scanning calorimetry (DSC) and hot-stage microscopy were used to assess the homogeneity of the formulations and to detect if there is any phase separation during processing and storage. Fourier transform infrared (FTIR) spectroscopy analysis was further used to assess any drug-excipients interactions.

Results: Solubility studies revealed that CA was highly soluble in Kolliphor® TPGS and Gelucire® 44/14, and solubility increased linearly as the concentration increased. All the extruded granules shofloating lag time of less than 5 seconds and floated for more than 12 h simulated gastric fluid. Optimized formulation was able to give a sustained drug release profile for 12 hours. Micromeritic properties of optimized formulation shogood flow properties compared to the pure drug. Surface characterization revealed that granules had a smooth surface indicating the presence of lipids on the surface. DSC and hot-stage microscopy studies confirmed that there was no phase separation between CA and the excipients. The FTIR studies shothat there was no major interaction between the CA and excipients studied.

Conclusion: Lipid-based gastro retentive floating drug delivery systems were prepared and shodesired sustained release profiles, which will ensure more complete dissolution of CA with potential improved absorption due to reduced enzymatic degradation and longer residence time in the stomach.

Concentration/Emphasis

Emphasis: Pharmaceutics

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