Campus Access Only
All rights reserved. This publication is intended for use solely by faculty, students, and staff of University of the Pacific. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher.
Date of Award
1997
Document Type
Dissertation - Pacific Access Restricted
Degree Name
Doctor of Philosophy (Ph.D.)
Department
Pharmaceutical and Chemical Sciences
First Advisor
Xiaoling Li
First Committee Member
Bret Berner
Second Committee Member
Donald Floriddia
Third Committee Member
Patrick Jones
Fourth Committee Member
William Kehoe
Abstract
Novel buccal mucoadhesive copolymers of acrylic acid (AA) and poly (ethylene glycol) monomethylether monomethacrylate (PEGMM), (P(AA-co-PEG)), were designed, synthesized, and characterized for systemic delivery of acyclovir across the buccal mucosa. To achieve spontaneous intimate contact between polymer and buccal mucosa, the surface properties of P(AA-co-PEG) were optimized for buccal adhesion by varying the composition of the copolymers. It was found that the mole ratio of the repeat units of PEG, ethylene glycol, to AA is of great importance for mucoadhesion. ATR-FTIR studies revealed that the PEG moiety enhanced intra- and intermolecular H-bond formation. The copolymer films containing 16 mole% PEGMM (PEG MW 400) and 1.3 wt% ethylene glycol dimethacrylate (EGDMA) yielded the most favorable mucoadhesive properties within the investigated range. Factors influencing drug loading included equilibrium hydration, crosslinking density, loading solution medium, and concentration of drug in loading solution. In vitro release studies, performed in isotonic McIlvaine buffer pH 6.8 (IMB), showed a Non-Fickian release behavior. The release of acyclovir from the buccal mucoadhesive films was controlled by a combination of diffusion and macromolecular chain relaxation mechanism. In vitro permeation studies were conducted to determine the buccal transport pathway of acyclovir and to investigate the feasibility of buccal delivery of the drug. The paracellular route was found as the dominant buccal transport route of acyclovir. Permeation enhancement of acyclovir across the buccal mucosa was investigated using 2-100 mM sodium glycocholate (SGC). In the presence of SGC, the drug permeability was enhanced 2 to 9 times. The mechanism of this enhancement was attributed to SGC facilitating the paracellular route. The feasibility of buccal delivery of acyclovir was demonstrated and controlled release was achieved for up to 12 hours from P(AA-co-PEG) devices with a unidirectional design. The rate-limiting barrier to drug delivery from the mucoadhesive device was found to be the buccal mucosa. The target flux for systemic delivery of acyclovir was achieved with the incorporation of SGC into the tailor-made mucoadhesive copolymers of acrylic acid and PEGMM.
Pages
203
ISBN
9780591309706 , 059130970X
Recommended Citation
Shojaei, Amir Hossein. (1997). Buccal mucoadhesive delivery system of acyclovir. University of the Pacific, Dissertation - Pacific Access Restricted. https://scholarlycommons.pacific.edu/uop_etds/2626
To access this thesis/dissertation you must have a valid pacific.edu email address and log-in to Scholarly Commons.
Find in PacificSearch Find in ProQuestIf you are the author and would like to grant permission to make your work openly accessible, please email
Rights Statement
In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
