Defense Date

3-17-2017

Graduation Date

Spring 1-1-2017

Availability

One-year Embargo

Submission Type

dissertation

Degree Name

PhD

Department

Pharmaceutics

School

School of Pharmacy

Committee Chair

Peter Wildfong

Committee Member

Ira Buckner

Committee Member

Wilson Meng

Committee Member

Lauren O'Donnell

Committee Member

Maureen Donovan

Committee Member

Rehana Leak

Keywords

Levodopa, Microparticles, Nasal Delivery, Ribavirin

Abstract

The objective of this work was to introduce a novel formulation strategy for intranasal delivery of two low permeation candidates: levodopa (L-DOPA; antiparkinsonism drug) and ribavirin (RBVN; an antiviral drug). The central hypothesis states that preparation of binary composite microparticles with Pluronic® triblock copolymers (polyethylene glycol-polypropylene glycol-polyethylene glycol) should allow increased drug transport across nasal mucosal tissue relative to drug alone. Testing the hypothesis necessitated execution of specific aims directed to addressing issues inherent to the proposed approach. The work herein is presented with respect to two separate subjects: (1) material understanding and (2) formulation development. In the first two chapters, the feasibility of direct deposition of dry, solid drug microparticles on intranasal permeation was explored. Further, specific emphasis was placed on selection of the most suitable solid form which can sustain the stresses of the chosen manufacturing processes.

The concluding part of this work is devoted to illustrating the use of binary composite polymeric microparticles, ultimately stemming from the materials and methodologies developed in the initial stages. The rate and extent of ribavirin transport was significantly higher from solid polymeric microparticles compared to standalone drug powder and its aqueous solution. Increased drug transport was attributable to permeation enhancement afforded by Pluronic® accompanied with a high initial concentration gradient established across the model tissue.

Format

PDF

Language

English

Download

Share

COinS