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
Language
English
Recommended Citation
Vasa, D. M. (2017). Development of Binary Composite Solid Microparticles for Improved Intranasal Absorption of Low Permeation Drug Molecules (Doctoral dissertation, Duquesne University). Retrieved from https://dsc.duq.edu/etd/152