Quantification of dermal and transdermal delivery of meloxicam gels in rabbits

Abstract

Background: This study was designed to quantify the effects of penetration enhancers on systemic bioavailability of 0.3% meloxicam (MLX) hydroxypropylcellulose gels. Cutaneous microdialysis was also performed to assess dermis availability and to better understand the penetration process. The gels tested were a 1% oleic acid gel, a 5% menthol gel, and a control gel without penetration enhancers.

Methods: To assess systemic bioavailability, three female rabbits received according to a crossover design 0.135 g/cm² of gel applied to a 7.5 × 7.5 cm area of their shaved back and a short (5 min) infusion of 1 mg. In each experiment, blood samples were collected serially for 36 h and analyzed by a validated HPLC method. For skin bioavailability studies, 0.135 g/cm² of the same gels were applied to a 1 × 2 cm area on top of a microdialysis probe previously inserted in the dermis. Dialysate samples were collected for 6 h every 30 min.

Results: Systemically, the 5% menthol gel delivered 3.93 ± 0.85 mg of MLX versus the 1.41 ± 0.24 mg of the oleic acid gel. Only traces of MLX were detectable from the control gel. In dermis, substantial concentrations of MLX were detected only after the application of the menthol gel, whereas skin concentration from the control gel and the 1% oleic acid gel were always below the lowest limit of quantification (LLOQ).

Conclusions: The 5% menthol gel can possibly deliver therapeutically relevant amount of MLX in vivo. Dermis concentrations can be predictive of systemic plasma levels.

Keywords::

• Meloxicam
• menthol
• microdialysis
• transdermal delivery
• bioavailability

Acknowledgement

The authors would like to express special thanks to Dr. Joanne van Ryn, Boehringer Ingelheim Pharma (Biberach, Germany) for the donation of MLX powder.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.