Enhancement of drug permeability in different skin models using physical and chemical techniques

Two types of hairless Peromyscus maniculatus mice (type-1 and type-2) were evaluated as an in vitro skin model for transdermal drug delivery studies and were compared to SKH-1 hairless mouse and human cadaver skins. The study contained the evaluation of the gender effect and the response of the skin to the effect of permeation enhancers such as Azone. The two types of Peromyscus mice were of the same magnitude of permeability as that of SKH-1 hairless mouse.; In the second part of the dissertation two classes of PEG based copolymers [poly(PEG-Lys-alkylamide)s and poly(PEG-DTR ether)s] were evaluated as potential permeation enhancers. The activity of fifteen copolymers was evaluated using hydrocortisone as a model drug. Three polymers (P-1, P5a, and P7) enhanced the permeation of hydrocortisone across hairless mouse skin. Factors affecting the activity of the enhancers such as concentration and vehicle were evaluated.; In the last part the feasibility of transdermal delivery of buspirone hydrochloride was evaluated in both SKH-1 hairless mouse and human cadaver skins in vitro using chemical (terpene enhancers) and physical (iontophoresis) enhancement techniques. Hairless mouse skin was more sensitive to the effect of terpenes. A 200-fold increase in the flux of buspirone was observed upon using 2% menthol as compared to the control. However 2% menthol showed no activity in human cadaver skin. Moreover, using iontophoresis at 0.5mA/cm2 current density, it was possible to deliver 7.5mg/cm2 of buspirone hydrochloride per day. However the iontophoretic flux of buspirone was directly proportional to the current density in the range between 0.1 to 0.5mA/cm2.