title: 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/cm(2) 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/cm(2) 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.
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 DeKalb Ave., Brooklyn, NY 11201, USA.
authors.forename: Mayurkumar
authors.initials: M
authors.lastname: Patel
authors.forename: Abhay
authors.initials: A
authors.lastname: Joshi
authors.forename: Hana
authors.initials: H
authors.lastname: Hassanzadeth
authors.forename: Ravi
authors.initials: R
authors.lastname: Juluru
authors.forename: Grazia
authors.initials: G
authors.lastname: Stagni
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005782:Gels / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077239:Meloxicam; D008610:Menthol / Q000737:chemistry; D017551:Microdialysis / Q000379:methods; D019301:Oleic Acid / Q000737:chemistry; D011817:Rabbits; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013047:Specific Pathogen-Free Organisms; D013843:Thiazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D005782:Gels; D013843:Thiazines; D013844:Thiazoles; D008610:Menthol; D019301:Oleic Acid; D002482:Cellulose; C008079:hydroxypropylcellulose; D000077239:Meloxicam