Transdermal self-permeation enhancement of ibuprofen.
The objective of this study was to prepare saturated solutions of ibuprofen, of different concentrations, and to investigate their effect on permeation of ibuprofen across rat epidermis. Ibuprofen saturated solutions were prepared using 0.1, 0.2, 0.3 and 0.4 M disodium hydrogen phosphate solution (DHP). The solubility of ibuprofen in DHP increased as the molarity of DHP increased. Thus the four saturated solutions of ibuprofen (0.1M-DHP-IBU, 0.2M-DHP-IBU, 0.3M-DHP-IBU and 0.4M-DHP-IBU) have different concentrations of the same drug, and showed same pH (pH 7.0+/-1). The permeability study was also carried out using human epidermis and silastic membrane. Permeation rate of ibuprofen across rat epidermis and human epidermis from 0.4M-DHP-IBU was much greater than from 0.1M-DHP-IBU. The magnitudes of increase in the drug flux were 46.4-fold with rat epidermis and 9.4-fold with human epidermis. Such a great increase in drug flux was not observed with silastic membrane, only 1.4-fold. This suggests that the increased drug flux is likely due to drug-skin interaction and not the increased concentration of ibuprofen per se. Surface tension (ST) measurements of DHP versus ibuprofen concentration showed ST reduction of DHP, from 72 to 27.9 dyn/cm. This is an indication that ibuprofen acted as ionic surfactant and the observed skin permeability enhancement is attributed to disruption of stratum corneum barrier. Results of DSC study supported this assumption. DSC of untreated rat stratum corneum samples showed lipid transitions at 41.9+/-0.0 degrees C (T1), 55.1+/-1.6 degrees C (T(x)), 70.2+/-0.1 degrees C (T2) and 77.5+/-0.1 degrees C (T3), while those pretreated with 0.4M-DHP-IBU did not show the first three lipid transitions. Also, pretreatment of rat epidermis with 0.4M-DHP-IBU enhanced permeation of diclofenac sodium greater than 1250-fold. This corroborates that ibuprofen not only enhances its own permeation but also that of other drugs, such as diclofenac sodium.
Al-Saidan
S M
SM
Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, SAFAT 13110, Kuwait. alsaidan@hsc.edu.kw
D000279:Administration, Cutaneous; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D019999:Pharmaceutical Solutions; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013500:Surface Tension; D013501:Surface-Active Agents; D013816:Thermodynamics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008567:Membranes, Artificial; D019999:Pharmaceutical Solutions; D013501:Surface-Active Agents; D004008:Diclofenac; D007052:Ibuprofen