Effect of formulation variables on the percutaneous permeation of ketoprofen from gel formulations.
The objectives of our study were to evaluate the effect of four terpene enhancers, enhancer lipophilicity, and ethanol concentration using hydroxypropyl cellulose (HPC) and two Pluronic F-127 (PF-127) gel formulations on the percutaneous permeation of ketoprofen. All experiments were conducted using hairless mouse skin in vitro. Data recorded over 24 hr was compared with that for control gels (containing no terpene) using Franz diffusion cells. In the three gel formulations, the highest increase in the ketoprofen permeation was observed using limonene followed by nerolidol, fenchone, and thymol. Relationships were established between terpene lipophilicity, enhancement ratios for ketoprofen flux (ERflux), and the cumulative amount of ketoprofen after 24 hr (Q24) from the three gel formulations. However, no correlation was established between terpene lipophilicity and ketoprofen skin content values at 24 hr. Ethanol had a synergistic effect on the enhancing activity of the terpenes. Increasing the concentration of ethanol from 10% to 50% was associated with an increase in the permeation of ketoprofen. For example, use of PF-127 gel control (no terpene was included) containing 10% ethanol resulted in a ketoprofen flux of 19 +/- 2 microg/cm2 h and 481 +/- 131 microg/cm2 for Q24. Furthermore, for PF-127 containing 33% ethanol the flux was 34 +/- 3 microg/cm2 h and Q24 was 1,420 +/- 111 microg/cm2. However, HPC gel control that contained 50% ethanol resulted in a ketoprofen flux of 67 +/- 6 microg/cm2 h and 2,839 +/- 222 microg/cm2 for Q24.
El-Kattan
A F
AF
Dept of Basic Pharmaceutical Sciences College of Pharmacy, University of South Carolina, Columbia 29208, USA.
Asbill
C S
CS
Kim
N
N
Michniak
B B
BB
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002482:Cellulose / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D000431:Ethanol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005079:Excipients / Q000493:pharmacokinetics; D005260:Female; D005782:Gels; D007660:Ketoprofen / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D020442:Poloxamer / Q000493:pharmacokinetics; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D012997:Solvents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013729:Terpenes / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D005782:Gels; D012997:Solvents; D013729:Terpenes; D020442:Poloxamer; D000431:Ethanol; D002482:Cellulose; D007660:Ketoprofen; C008079:hydroxypropylcellulose