3mL. The cumulative amount of DE permeated through skin was plotted versus time (h). Each data was expressed as mean ± SD of three determinations. The steady-state flux value (Jss) was calculated from the slope of linear portion of cumulative amount permeated-time plots for a zero-order model and expressed as the mass of DE passing across 1cm2 of skin over time. The enhancement ratio (ER) was determined using the following equation: ER=Flux  (with  enhancer)Flux  (without  enhancer)  . (2) 2.5.

Characterization of Developed MDTS Formulations The qualitative tests performed for the MDTS formulations included the evaluation of spray pattern, effectiveness Inhibitors,research,lifescience,medical of pump seal, average weight per metered dose, and content uniformity [13]. The spray pattern was assessed by delivering the spray through the MDTS onto paper. To maintain a constant distance between the point of Inhibitors,research,lifescience,medical exit of the spray from the device to the paper, the container was fixed

by a fixator for every actuation. The formulation was held at a distance of 5cm from the paper. The wet part formed was outlined, then the outlined part was clipped from the paper and weighted. Effectiveness of the pump seal was evaluated by pump Inhibitors,research,lifescience,medical seal efficiency test. The filled containers under test were placed in the upright position at 30° for 3 days. The containers were weighed before and after the test period. The change in the weight of the container was recorded Inhibitors,research,lifescience,medical and the leakage rates were calculated. Average weight per metered dose was measured. The initial weight of the container was

recorded; then the container was weighed again after successive deliveries were sprayed from the MDTS. The difference between the initial and final weight of the container divided by the number of delivery sprayed from the containers was used to determine the average weight per metered dose. The DE content per spray was determined by actuating designed sprays in a beaker containing methanol. Then the drug content was analyzed by HPLC. The drug LY411575 concentration administration area of each pump was calculated by the following equation: Ax=Wo×AoWx, (3) where Wo and Ao are Inhibitors,research,lifescience,medical the known weight and area, respectively, of the paper we clipped from the paper, Wx is the weight of the paper after certain MDTS actuation, and Ax is the area of certain pump. Taking paper with area of 10cm × 10cm and weighted 0.8166g as a sample, Wo is 0.8166g and Ao is 100cm2. The pump seal efficiency was calculated by the following equation: Leakage  rate=(Wbefore  test−Wafter  test)Wbefore  test; (4) Wbeforetest and Waftertest Oxygenase were the weight of the container before and after the test period, respectively. Average weight per metered dose was measured by the following equation: Wn−m=(Wn−Wm)(m−n)×100%, (5) where Wn and Wm were the weight of the “n” and “m” actuation times, respectively. Wn−m was the average weight per metered dose during the “n” to “m” actuation times. 2.6. Pharmacokinetic Study Healthy female Sprague-Dawley rats weighing 240 ± 20g were used in this study.