Effects of penetration enhancers on in vitro permeability of meloxicam gels.
Meloxicam (MLX) was formulated as a 0.3% hydroxypropylcellulose (Klucel) gel. The effect of four different combinations of co-solvents (ethanol, glycol-PEG-400, propylene glycol, and water) on MLX permeability was determined in vitro throughout isopropyl myristate (IPM)-saturated cellulose membranes. The gel consisting of 2.5% Klucel, propylene glycol, ethanol, and water (1:1:1) showed superior permeability properties and it was selected as the base-gel to investigate the effect of three levels of the penetration enhancers: dimethylsulfoxide (1, 5, and 10% DMSO), tween20 (1, 2, and 5% TW20), oleic acid (0.4, 1, and 5% OA), and menthol (1, 2.5, and 5% MT). In vitro permeability was determined throughout IPM-saturated cellulose membranes and human cadaver skin. DMSO and TW20 did not improve permeability of MLX compared to the control gel at any of the levels tested. Menthol produced a statistically significant (P<0.001), dose proportional increase in MLX flux with a peak at 5% (2.43+/-0.47 microg/cm2/h). Conversely, addition of OA peaked at 1% but decreased at the higher level (5%). There was no significant difference between the MLX amount recovered in stratum corneum and dermis across the different formulations tested. These findings show that the 0.3% MLX gel formulation containing 5% menthol can possibly deliver therapeutically relevant doses of MLX.
Jantharaprapap
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Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 DeKalb Ave., Brooklyn, NY 11201, USA.
Stagni
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D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism*; D002482:Cellulose; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D000431:Ethanol / Q000737:chemistry / Q000378:metabolism; D005782:Gels; D006801:Humans; D066298:In Vitro Techniques; D000077239:Meloxicam; D008567:Membranes, Artificial; D008610:Menthol / Q000494:pharmacology*; D009226:Myristates; D019301:Oleic Acid / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011136:Polysorbates / Q000494:pharmacology; D019946:Propylene Glycol / Q000737:chemistry / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012997:Solvents / Q000737:chemistry / Q000378:metabolism; D013843:Thiazines / Q000008:administration & dosage / Q000378:metabolism*; D013844:Thiazoles / Q000008:administration & dosage / Q000378:metabolism*; D014867:Water / Q000737:chemistry / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D008567:Membranes, Artificial; D009226:Myristates; D011136:Polysorbates; D012997:Solvents; D013843:Thiazines; D013844:Thiazoles; D014867:Water; C008205:isopropyl myristate; D008610:Menthol; D019301:Oleic Acid; D000431:Ethanol; D011092:Polyethylene Glycols; D019946:Propylene Glycol; D002482:Cellulose; D000077239:Meloxicam; D004121:Dimethyl Sulfoxide