Retraction of Rizal

Drug Development and Industrial Pharmacy, 2011; 37(5): 613–617 © 2011 Informa Healthcare USA, Inc. ISSN 0363-9045 print/ISSN 1520-5762 online DOI: 10.3109/03639045.2010.534098

ORIGINAL ARTICLE

Quantification of dermal and transdermal delivery of meloxicam gels in rabbits
Mayurkumar Patel1,2, Abhay Joshi1, Hana Hassanzadeth1,3, Ravi Juluru1, and Grazia Stagni1
1

Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA, 2Current affiliation: International Trading Pharmaceutical Laboratories Inc, Paterson, NJ, USA, and 3Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
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

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N Engl J Med 340:1888–1899. Figure 3. Average unbound concentration of meloxicam in dermis (n = 6) and plasma (n = 3) following the application of the 0.3% meloxicam (MLX) gel containing 5% menthol as penetration enhancer. Plasma data were normalized by the size of the delivery area. where plasma levels were also extremely low during the first 6 h. In order to compare the skin concentrations detected from the 5% menthol gel application with the plasma concentrations, as in Figure 3, the plasma concentrations were transformed to unbound concentrations (fraction unbound = 0.01) and then divided by 28.125 that is the ratio between the application area of the gel in the systemic availability studies (7.5 × 7.5 cm) and the area for skin availability studies (1 × 2 cm). Figure 3 shows that the skin concentration reaches a plateau at approximately 2–3 hours, remains at plateau for 3–4 h, and drops thereafter. MLX in plasma reaches a plateau with a delay of about 1 h compared with the skin. Therefore, the dermis appears to work as an intermediate (depot) compartment in which MLX accumulates before diffusing to plasma. Figure 3 also shows that both plasma and skin concentration profiles have a large degree of variability when menthol is used as penetration enhancer. This was observed with other NSAID such as ibuprofen (Brain et al., 2006). Indeed, skin availability experiments were performed in six rabbits compared with the three planned at the beginning of the study. It was also observed by visual inspection that when menthol was present, rabbit skin tended to swallow and become hydrated and soft but to a different extent between experiments. Conclusions The results of this study confirmed in vivo the relative magnitude of delivery as previously found in the in vitro study (Jantharaprapap and Stagni, 2007) and that a 5% menthol gel can possibly deliver therapeutically relevant doses of MLX. In addition, the study suggests that dermis dialysate may be predictive of systemic bioavailability. Copyright of Drug Development & Industrial Pharmacy is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder 's express written permission. However, users may print, download, or email articles for individual use.