Electronic Theses and Dissertations

Date of Award

1-1-2015

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Biomolecular Sciences

First Advisor

Soumyajit Majumdar

Second Advisor

John O'Haver

Third Advisor

S. Narasimha Murthy

Relational Format

dissertation/thesis

Abstract

A large number of pharmaceutical compounds belong to class II and IV of biopharmaceutical classification of drug (BCS). Class II compounds are limited by their poor aqueous solubility, while class IV compounds suffer from poor solubility and permeability. This translates to poor absorption and low plasma levels post oral administration. Lipids comprise of fatty acids and their derivatives and are considered a biocompatible option for drug delivery. In the studies discussed in following chapters, lipid based drug delivery systems (LBDDS) have been utilized in improving the handling, ease of formulation, solubility and bioavailability of three compounds. In the first study, studies have been performed to formulate Δ9-THC into a sustained release tablet, using lipid matrices, for the treatment of chemotherapy induced nausea and vomiting (CINV). In the second study, LBDDS such as solid lipid nanoparticles were prepared for non-invasively enhancing the ocular penetration of Δ8-THC for the treatment of Glaucoma. In the third study, the handling and oral bioavailability of dihydroartemisinin dimer oxime was studied using various lipid based systems for potential use in the treatment of malaria.

The lipid based tablet formulation of Δ9-THC was successful in achieving a 24 hour release profile and can be potentially be used as a one dose per day medication for CINV. The topical ocular penetration of Δ8-THC significantly when formulated as solid lipid nanoparticles and the drug was able to reach the posterior ocular segments, with levels being maintained at the end of three hours. The dimer oxime was able to achieve an 8 hour plasma profile through various lipid based systems and these levels were above the IC50 values of the malarial parasite. The tested prodrug showed a lot of promise and further optimization of these formulations would help in developing a new line of malarial therapy.

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