Bret Berner

Transbuccal delivery of acyclovir : I. In vitro determination of routes of buccal transport

AbstractPurpose. To determine the major routes of buccal transport of acyclovir and to examine the effects of pH and permeation enhancer on drug permeation. Methods. Permeation of acyclovir across porcine buccal mucosa was studied by using side-by-side flow through diffusion cells at 37°C. The permeability of acyclovir was determined at pH range of 3.3 to 8.8. Permeability of different ionic species was calculated by fitting the permeation data to a mathematical model. Acyclovir was quantified using HPLC. Results. Higher steady state fluxes were observed at pH 3.3 and 8.8. The partition coefficient (1-octanol/buffer) and the solubility of acyclovir showed the same pH dependent profile as that of drug permeation. In the presence of sodium glycocholate (NaGC) (2−100 mM), the permeability of acyclovir across buccal mucosa was increased 2 to 9 times. This enhancement was independent of pH and reached a plateau above the critical micelle concentration of NaGC. The permeabilities of anionic, cationic, and zwitterionic species were 3.83 × 10−5, 4.33 × 10−5, and 6.24 × 10−6cm/sec, respectively. Conclusions. The in vitropermeability of acyclovir across porcine buccal mucosa and the octanol-water partitioning of the drug were pH dependent. A model of the paracellular permeation of the anionic, cationic, and zwitterionic forms of acyclovir is consistent with these data. The paracellular route was the primary route of buccal transport of acyclovir, and the enhancement of transbuccal transport of acyclovir by sodium glycocholate (NaGC) appeared to operate via this paracellular route.

Design and Simulation of a Reverse Iontophoretic Glucose Monitoring Device

Mathematical modeling is presented for a combined iontophoretic device and biosensor used to analyze glucose concentration in transdermally extracted fluid that is correlated to blood glucose. This device works as follows: an electric current (iontophoresis) is used to extract glucose across the skin into a hydrogel. Within the hydrogel, the extracted glucose undergoes a reaction with the enzyme, glucose oxidase (GOx), to produce gluconic acid and hydrogen peroxide in the presence o oxygen. The hydrogen peroxide then further diffuses to and reacts on a platinum electrode to produce two electrons, water, and oxygen. The measured electrical current is proportional to the flux of glucose entering the hydrogel. Modeling for this device involves the diffusion of (a- and β-) glucose and hydrogen peroxide in the hydrogel, as well as the reaction of β-glucose with GOx, the mutarotation of the α-, β-anomeric pair, and the oxidation of hydrogen peroxide on a platinum catalyst/electrode. The reaction-diffusion problem exhibits both axial and radial diffusion as well as discontinuous boundary conditions, requiring the use of finite element methods to perform the simulations.