Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream

Abstract

Introduction: During recent years, there has been growing interest in use of topical vehicle systems to assist in drug permeation through the skin. Drugs of interest are usually those that are problematic when given orally, such as piroxicam, a highly effective anti-inflammatory, anti-pyretic, and analgesic, but with the adverse effect of causing gastrointestinal ulcers. The present study investigated the in vitro and in vivo pharmacodynamic activity of a newly synthesized palm oil esters (POEs)-based nanocream containing piroxicam for topical delivery.

Methods: A ratio of 25:37:38 of POEs: external phase: surfactants (Tween 80:Span 20, in a ratio 80:20), respectively was selected as the basic composition for the production of a nanocream with ideal properties. Various nanocreams were prepared using phosphate-buffered saline as the external phase at three different pH values. The abilities of these formulae to deliver piroxicam were assessed in vitro using a Franz diffusion cell fitted with a cellulose acetate membrane and full thickness rat skin. These formulae were also evaluated in vivo by comparing their anti-inflammatory and analgesic activities with those of the currently marketed gel.

Results: After eight hours, nearly 100% of drug was transferred through the artificial membrane from the prepared formula F3 (phosphate-buffered saline at pH 7.4 as the external phase) and the marketed gel. The steady-state flux through rat skin of all formulae tested was higher than that of the marketed gel. Pharmacodynamically, nanocream formula F3 exhibited the highest anti- inflammatory and analgesic effects as compared with the other formulae.

Conclusion: The nanocream containing the newly synthesized POEs was successful for trans-dermal delivery of piroxicam.

Keywords: analgesic; anti-inflammatory; nanocream; piroxicam; skin permeation.

Figure 1

Comparative mean in vitro cellulose acetate membrane transport profiles of piroxicam from formulations F2, F3 and reference gel. Note: Mean ± S.D., N = 3.

Figure 2

Comparative mean in vitro rat skin permeation profiles of piroxicam from formulations F2, F3 and reference gel. Note: Mean ± S.D., N = 3.

Figure 3

The effect of topical administration of different formulations of piroxicam on rat hind paw edema at 2, 4 and 6 hours after administration of carrageenan. Notes: *** and ** indicate significant at P < 0.001 and P < 0.01, respectively. Mean ± S.D., N = 6.

Figure 4

The effect of topical administration of different formulations of piroxicam on rat hind paw hyperalgesia at 2 and 4 hours after administration of carrageenan. Notes: *** and ** indicate significant at P < 0.001 and P < 0.01, respectively. Mean ± S.D., N = 6.