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Date of Award


Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)


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


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.




9780591309706 , 059130970X

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