Abstract
The skin provides an effective barrier and only limited number of drugs can penetrate in adequate amounts. This study aims to identify the relationship between the physicochemical properties and permeation across mouse skin of non-steroidal anti-inflammatory drugs in view of their feasibility to transdermal delivery. Biphenylacetic acid, diclofenac base, diclofenac sodium, indomethacin and piroxicam are the drugs studied. Number of physicochemical properties studies were performed. Drug permeation studies across hairless mouse skin were carried out using an in-vitro finite dosing diffusion cell. The relationship between physicochemical properties of the drugs studied and their percutaneous penetration was studied. Purity for the compounds studied ranged from 99.09% to 100% in which 99.89% purity was obtained for diclofenac base. At 7.4, the % ionized of piroxicam was found to be 95.12%, while for other drugs were in the range of 98.01% and 99.96%. The true partition coefficient values in the n-octanol/water system are in the range of 1.85 and 2.85, while in the n-octanol/phosphate system ranged from 2.14 to 3.70. Observed solubility in water, phosphate buffer and noctanol ranged from 0.033 to 0.322, 0.202 to 0.329 mg per ml, and 2.19 to 16.10 mg per ml, respectively. A linear relationship was found between water solubility and melting point between steady-state rates of permeation across intact and viable skin, between n-octanol solubility and maximum predicted flux and between molecular volume and the ratio of maximum predicted flux. Predicted flux calculated was compared with the experimental data which resulted in a high correlation. Physicochemical criteria which were determined the feasibility of nonsteroidal anti-inflammatory drugs studied for transdermal delivery were identified. The relationships obtained in this study provide an essential physical and chemical properties that govern transport of non-steroidal anti-inflammatory drugs across hairless mouse skin.