In-vitro transcutaneous delivery of ketoprofen and polyunsaturated fatty acids from a pluronic lecithin organogel vehicle containing fish oil.
This work explored the use of pluronic lecithin organogel (PLO) as a base for the delivery of bioactive polyunsaturated fatty acids from fish oil, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and ketoprofen. PLO was adapted to contain fish oil, ketoprofen, or both, and 1,8-cineole as penetration enhancer, and used to determine the in-vitro permeation from infinite and finite dosing protocols across full thickness porcine skin. Oruvail gel (2.5% ketoprofen) was included for comparison. No EPA or DHA was found to permeate skin when applied as an infinite dose. From multiple finite doses, small amount (max. 0.22%) of fish oil were found to permeate the skin. This indicates retention of fish oil within the gel matrix and that the viable domain of full thickness skin was a significant barrier. Greater amounts of EPA and DHA were delivered in the presence of ketoprofen indicating co-transport resulting from selective complexation, although no enhancement was observed using 1,8-cineole. Unlike EPA and DHA, substantial amounts of ketoprofen permeated when applied as infinite doses. Oruvail, a Carbopol 940-based hydrogel containing 2.5% ketoprofen and ethanol, delivered the greatest amount, although similar to the PLO gel containing 5% ketoprofen. The addition of propylene glycol enhanced permeation, although the presence of fish oil in the PLO gel inhibited ketoprofen permeation. When applied as multiple finite doses a maximum of 76 microm cm(-2) (1.12%) was delivered, which was reduced by the presence of 1,8-cineole. Greater permeation was again observed with Oruvail by a factor of two and with half the ketoprofen dose. To conclude, a PLO-based gel is capable of delivering EPA and DHA via a repeat finite dosing regimen, although there is evidence for the retention of these very lipophilic molecules within the gel matrix. Although to a lesser extent than EPA and DHA, ketoprofen was also substantially retained, as exemplified by the superior delivery rates from Oruvail. Finally, this work has highlighted the importance of using an appropriate topical dosing method to match the intended use of a product.
Richards
Helen
H
Welsh School of Pharmacy, Cardiff University, CF10 3XF, UK.
Thomas
Christopher P
CP
Bowen
Jenna L
JL
Heard
Charles M
CM
D000279:Administration, Cutaneous; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005395:Fish Oils / Q000737:chemistry*; D005782:Gels; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010713:Phosphatidylcholines / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine
D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D005782:Gels; D010713:Phosphatidylcholines; D020442:Poloxamer; D007660:Ketoprofen