Effect of Receptor Solution in Studies of In Vitro Permeation Test (IVPT).

In Vitro Permeation Test (IVPT) is commonly used to evaluate skin penetration of chemicals and performance of dermatological products. For a permeant with low aqueous solubility, an additive that is expected not to alter the skin barrier can be used in the receptor solution to improve permeant solubility. The objective of this study was to (a) evaluate the effects of these additives in IVPT receptor solution on skin permeability of model permeants and skin electrical resistance and (b) determine the solubility of the permeants in these receptor solutions. Bovine serum albumin (BSA), 2-hydroxypropyl-beta-cyclodextrin (HPCD), ethanol, nonionic surfactant Brij-98, and propylene glycol were the additives, and phosphate buffered saline (PBS) was the control. Steady-state skin permeability coefficients and resistances were determined. The receptor solutions examined in this study did not cause a significant increase in skin permeability or decrease in resistance (less than 40 % changes) except 25 % ethanol. The receptor solution containing 25 % ethanol induced an approximately twofold average increase in skin permeability and reduced skin electrical resistance by approximately threefold. The receptor solution of 2.5 % HPCD provided the highest levels of solubility for the model lipophilic permeants, while 0.2 % Brij-98 and 5 % ethanol showed the lowest solubility enhancement from those in PBS.

Permeability of Fresh and Frozen Porcine and Human Gingiva and the Effect of Storage Duration.

The gingiva is the target site for some topical drugs, but the permeability of human gingiva has not been systematically evaluated. Pigs are a common animal model for in vitro membrane transport studies. The objectives of this study were to: (a) determine the permeability coefficients of freshly excised human gingiva using model permeants, (b) compare the permeability coefficients of fresh human gingiva with those of fresh porcine gingiva, (c) evaluate the effect of freezing duration on the permeability of porcine gingiva, and (d) compare the permeability coefficients of fresh and cadaver (frozen) human gingiva. A goal was to examine the feasibility of using porcine gingiva as a surrogate for human gingiva. The potential of using frozen tissues in permeability studies of gingiva was also examined. Fresh and frozen porcine gingiva, fresh human gingiva, and frozen cadaver human gingiva were compared in the transport study with model polar and lipophilic permeants. The fresh porcine and human tissues showed similarities in the "permeability coefficient vs. octanol-water distribution coefficient" relationship. The porcine gingiva had a lower permeability than that of the human, with a moderate correlation between the permeability of the fresh porcine and fresh human tissues. The permeability of the porcine tissues for the model polar permeants increased significantly after the tissues were frozen in storage. Moreover, the frozen human cadaver tissue could not be utilized due to the high and indiscriminating permeability of the tissue for the permeants and large tissue sample-to-sample variabilities.

Iontophoresis on Porcine and Human Gingiva.

PURPOSE: Iontophoresis is a noninvasive method that enhances drug delivery using an electric field. This method can improve drug delivery to the tissues in the oral cavity. The effects of iontophoresis on gingival drug delivery have not been investigated. The objectives of this study were to (a) determine the flux enhancement of model permeants across porcine and human gingiva during iontophoresis, (b) examine the transport mechanisms of gingival iontophoresis, and (c) evaluate the potential of iontophoretically enhanced delivery for three model drugs lidocaine, ketorolac, and chlorhexidine. METHODS: Passive and iontophoretic fluxes were determined with porcine and human gingiva using a modified Franz diffusion cell and model drugs and permeants. To investigate the transport mechanisms of iontophoresis, the enhancement from the direct-field effect was determined by positively and negatively charged model permeants. The electroosmosis enhancement effect was determined with neutral permeants of different molecular weight. The alteration of the gingival barrier due to electropermeabilization was evaluated using electrical resistance measurements. RESULTS: Significant flux enhancement was observed during gingival iontophoresis. The direct-field effect was the major mechanism governing the iontophoretic transport of the charged permeants. Electroosmosis was from anode to cathode. The effective pore radius of the iontophoretic transport pathways in the porcine gingiva was ~0.68 nm. Irreversible electropermeabilization was observed after 2 and 4 h of iontophoresis under the conditions studied. CONCLUSION: Iontophoresis could enhance drug delivery and reduce transport lag time, showing promise for gingival drug delivery.

Lateral Transport During Membrane Permeation in Diffusion Cell: In Silico Study on Edge Effect and Membrane Blocking.

Membrane transport in diffusion cell studies is not one-dimensional from the donor to the receptor. Lateral diffusion within the membrane into the surrounding clamped region can lead to edge effect. Lateral diffusion can also affect the impact of an object blocking the membrane in a diffusion cell. The effects of lateral transport on permeation across a two-layer membrane in diffusion cells were investigated in this study under edge effect and membrane blocking conditions that could be encountered in previous gingiva and hypothetical skin permeation studies. Model simulations of time-dependent and steady-state transport were performed using COMSOL Multiphysics. The simulations indicated edge effect could increase the steady-state flux across the membrane up to 35% with a relatively thick membrane and small diffusion cell opening (e.g., gingiva study). The edge effect decreased when the relative thickness and permeability of the major barrier (top layer in the two-layer membrane) decreased. When the membrane was partially blocked by an object, lateral diffusion within the membrane could mitigate its impact: e.g., when the object was in the receptor, the impact caused by membrane blocking was reduced more than half. Therefore, membrane lateral transport should be considered under certain circumstances in permeation studies using diffusion cells.

Characterization of Porcine Gingiva for Drug Absorption.

Gingiva or gum is a part of the periodontium that surrounds the tooth. Its main function is to provide an effective barrier to both mechanical trauma and bacterial invasion. Gingiva is the target site for some topical drugs. The most common disease in gingiva is periodontal diseases (gum infections). Understanding the gingiva barrier properties could provide insights into approaches to effective drug delivery for the gingiva. Porcine gingiva was chosen as the model in the present membrane transport study. The permeability coefficients of gingiva were determined using a modified Franz diffusion cell with small diffusional area (0.03 cm2) and 12 model permeants with different physicochemical properties. The influences of edge effect and aqueous boundary layers were not observed in the modified diffusion cell setup for the small pieces of gingiva tissue samples. Lipophilic permeants exhibit higher permeability coefficients than hydrophilic permeants. A correlation was observed between the Log permeability coefficient (Log P) and Log octanol-water distribution coefficient (Log Dow) in the analysis. The permeant molecular weight (MW) was also a factor in the Log P vs. Log Dow relationship. The coefficient of Log Dow in this three-factor relationship (0.42) suggested that the gingiva barrier was less lipophilic than octanol.