Development of Binary Composite Solid Microparticles for Improved Intranasal Absorption of Low Permeation Drug Molecules

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. <p>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.

Name thesis:degree_name

PhD

Level thesis:degree_level

One-year Embargo

Discipline thesis:degree_discipline

Pharmaceutics

Year dc:date.available

2017

Author dc:creator

• Vasa, Dipy Madhukar

Contributors dc:contributor

• Peter Wildfong
• Ira Buckner
• Wilson Meng
• Lauren O'Donnell
• Maureen Donovan
• Rehana Leak

• Levodopa
• Microparticles
• Nasal Delivery
• Ribavirin

Language dc:language

English

Repository record dc:identifier

https://dsc.duq.edu/etd/152

OAI identifier oai:identifier

oai:dsc.duq.edu:etd-1151