Electronic Theses and Dissertations

Date of Award

2019

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

Department

Pharmaceutics and Drug Delivery

First Advisor

Chalet Tan

Second Advisor

Walt Chambliss

Third Advisor

Seongbong Jo

Relational Format

dissertation/thesis

Abstract

Parasitic diseases are a severe threat to people and animals. Praziquantel is the most common anti-parasitic drug with high efficiency, and it has been used to treat parasitic diseases for many years. However, it has very strong gastrointestinal and liver metabolism that leads to a strong first-pass effect and a short half-life. Additionally, the frequent oral administration was inconvenient for the large livestock. To overcome these drawbacks, this study aimed to develop an extended-release thermosensitive hydrogel formulation that was applicable to the injectable administration. The praziquantel-loaded hydrogel formulation based on poloxamer 407 (20%, w/v) was prepared, and two strategies for modifications of poloxamer 407 hydrogel were studied. One of them was the formulation consisting of PEG-DSPE/TPGS mixed micelles-poloxamer 407 hydrogel hybrid system; another was the poloxamer 407 hydrogel adding with HPMC as an adhesive. These hydrogel formulations had a reversible sol-gel transition property at approximate 26 °C and obtained high loading efficiencies and storage stability. in-vitro release studies, as well as in-vivo pharmacokinetic studies, were conducted to evaluate the extended-release effect, and the bioavailability of several optimized formulations of praziquantel was calculated. The in-vitro release of praziquantel was prolonged when loading into poloxamer 407 hydrogel. Both the modifications of poloxamer 407 hydrogel, by adding HPMC as well as utilizing PEG- DSPE/TPGS mixed micelle as a secondary delivery vehicle obtained the relatively better extended-release profiles than the original poloxamer 407 hydrogel. The pharmacokinetic studies indicated that the poloxamer 407 hydrogel formulation has a relatively high bioavailability and prolonged release profile, but both two modifications failed to obtain a significant improvement of an extended-release characteristic compared with the original hydrogel solution.

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