Date of Award

2007

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Bhaskara R. Jasti

First Committee Member

Xiaoling Li

Second Committee Member

S. Indiran Pather

Third Committee Member

Silvia Rodriguez

Fourth Committee Member

David Thomas

Abstract

Porcine buccal mucosa has been extensively used as in vitro model to study the permeability of drugs and assess their potential to deliver through buccal route. Porcine buccal mucosa is found to be very similar to human oral mucosa in structure and function. However, the in vitro permeation studies across porcine buccal mucosa show high variability which is mostly due to the various experimental and biological variables that are often overlooked while conducting such studies.

The precise nature of the permeability barrier offered by the various tissue layers of buccal mucosa was investigated in this study. It was observed that the permeability of model diffusants decreased significantly with an increase in the connective tissue layer. However, the epithelium offered a stronger barrier to permeation of all diffusants studied at mucosal thickness of up to 500 |tm. The epithelium acted as a stronger barrier for hydrophilic diffusants when compared to lipophilic diffusants.

It was also observed that the permeability of model diffusants was significantly higher in the region behind lip when compared to the middle cheek region which is due to lower epithelial thickness in that region. Porcine buccal mucosa retained its integrity in Kreb's bicarbonate Ringer solution at 4 °C for 24 hours and many other storage conditions resulted in loss of epithelial integrity. Separation of epithelium from the underlying connective tissue by heat treatment, did not adversely affect its permeability and integrity characteristics.

Influence of experimental temperature on the permeability of model compounds across porcine buccal mucosa was also investigated in vitro. An exponential relationship was observed between the apparent permeability and temperature. It was found that the activation energy of diffusion of the model compounds decreased linearly with increasing distribution coefficients across porcine buccal mucosa. This suggested that the buccal mucosa acted as a stronger barrier for diffusion of hydrophilic diffusants when compared to the lipophilic diffusants.

Pages

163

Share

COinS