In vitro, ex vivo, and in vivo evaluation of the effect of saturated fat acid chain length on the transdermal behavior of ibuprofen-loaded microemulsions.
In this study, the effect of the saturated fatty acid (FA) chain length in the oil phase on the behavior of Ibuprofen (IBU)-loaded transdermal microemulsion (ME) was evaluated in vitro, ex vivo, and in vivo. Three oils classified as long (LFA), medium (MFA), and short (SFA) chain length oils, Cremophor RH40 (surfactant) and Transcutol P (cosurfactant) were selected after experimental optimization. The physicochemical properties of ME were characterized, including IBU solubility in excipients, pseudo-ternary phase diagram construction, particle size, zeta potential, viscosity, and stability. Permeation flux and residual amount of IBU ex vivo using Franz cell system occurred in the following order: MFA-based ME > LFA-based ME > SFA-based ME, which correlated well with the results of confocal scanning laser microscopy study and the in vivo retention study. The results of in vitro cytotoxicity study and skin irritation tests measured by differential scanning calorimetry were ranked in the following order: LFA-based ME > MFA-based ME > SFA-based ME. Moreover, MFA-based ME has the highest analgesic activity among all the treatment groups. MFA was found to be an optimal oil phase with appropriate FA chain length for IBU-loaded transdermal ME, which exhibited excellent physicochemical properties, low toxicity, and good permeability profile.
Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
Qiuyue
Q
Ren
Chunli
C
Deng
Lin
L
Meng
Yanzuo
Y
Chen
Liangcen
L
Chen
Xianyi
X
Sha
Xiaoling
X
Fang
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions; D005227:Fatty Acids / Q000737:chemistry*; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D012867:Skin / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D005227:Fatty Acids; D007052:Ibuprofen
co-surfactant; emulsion; oil phase; permeability; surfactant; transdermal drug delivery system