Transdermal and transbuccal delivery of small molecules

Purpose. The aim of this research project was to evaluate the transdermal and transbuccal delivery of small molecules into/across the skin and to investigate transbuccal delivery of nicotine.;Methods. Three therapeutic drugs including adapalene, lidocaine hydrochloride and nicotine bitartrate were used in this project. Microemulsion formulation of adapalene was developed and evaluated for transfollicular delivery. A pseudoternary phase diagram was developed for microemulsion consisting of oleic acid as oil phase, tween 20 as surfactant, TranscutolRTM as cosurfactant, and deionized water. Differential tape stripping and confocal laser scanning microscopy were performed to determine the penetration of microemulsion through hair follicles. Transmission electron microscopy, dynamic light scattering, polarizing light microscopy, and differential scanning calorimetry were performed to characterize the microstructures of microemulsion. The pH and viscosity of the microemulsions were also determined. Permeation studies were carried out in vitro on porcine ear skin over a period of 24 h using Franz diffusion cells. Iontophoretic delivery of local anesthetic lidocaine hydrochloride through porcine skin was investigated. The effects of modulated alternative and direct current iontophoresis on the delivery of lidocaine hydrochloride were also evaluated.;Transbuccal delivery of nicotine bitartrate was investigated using porcine buccal mucosa. Silicone membrane and stripped skin were also evaluated as alternative membrane for porcine buccal mucosa to understand nicotine permeation. Histological studies were also conducted to evaluate the effect of storage conditions on the integrity of fresh and stored buccal mucosa. Effect of pH on permeation profile of nicotine was also performed. Effect of Nicorette lozenges on pH of artificial saliva and surface pH of the lozenges was also measured. An in vitro model was developed to evaluate real time release, permeation through silicone membrane and pH of nicotine lozenges.;Results and Conclusions. The results obtained from differential tape stripping and confocal microscopy studies show that adapalene microemulsions penetrated into the hair follicles. Differential scanning calorimetry study determined the thermal behavior and phase transition of microemulsion from water in oil to bi-continuous microemulsion. The results demonstrated that microemulsions are promising vehicle for transfollicular delivery of adapalene. Modulated iontophoresis enhanced the delivery of lidocaine hydrochloride across porcine skin compared to the passive delivery. Modulated alternative current iontophoresis for duration of 2 h at frequency of 1kHz was found to be comparable to the continuous direct current iontophoresis for lh.;Results of transbuccal delivery of nicotine and effect of pH on permeation of nicotine through buccal mucosa, demonstrates that ionization of nicotine occurs at pH 5.8, leading to less permeation of nicotine compared to pH 7.4 and 8.0. Our results also showed that silicone membrane and stripped skin could be used as potential alternative membrane for porcine buccal mucosa to understand nicotine permeation. An in vitro model was also successfully developed to evaluate real time release, permeation through silicone membrane and pH of nicotine lozenges.