Formulation optimization of meloxicam sodium gel using response surface methodology.
The influences of a combination of different mechanisms of penetration enhancers on the penetration absorption properties of meloxicam sodium formulations through rat skin were investigated using response surface methodology. A uniform design was applied to prepare model formulations systematically that were composed of four independent variables: the content of ethanol (x(1)), propylene glycol (x(2)), menthol (x(3)), and azone (x(4)). The penetration rate (flux) of meloxicam sodium gel through rat skin was chosen as the response which had to be higher than 400microg/hcm(2) the required flux of meloxicam gel to maintain a therapeutic concentration. The result showed optimal formulation could be obtained from this response surface methodology. Menthol had the greatest potential influence on the penetration absorption of meloxicam sodium, followed by azone, ethanol and PG, respectively. By in vivo study, meloxicam could be determined 1h after topical administration and reached steady-state concentration at about 12h. The bioavailability (%) of the optimal meloxicam sodium gel was about 50.1%.
Chang
Jui-Sheng
JS
Graduate Institute of Pharmaceutical Science, College of Pharmacy, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung City 80708, Taiwan, Republic of China.
Huang
Yaw-Bin
YB
Hou
Sen-Sen
SS
Wang
Ren-Jiunn
RJ
Wu
Pao-Chu
PC
Tsai
Yi-Hung
YH
D000042:Absorption; D000818:Animals; D002626:Chemistry, Pharmaceutical; D005782:Gels; D000077239:Meloxicam; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism; D012995:Solubility; D013843:Thiazines / Q000008:administration & dosage* / Q000737:chemistry; D013844:Thiazoles / Q000008:administration & dosage* / Q000737:chemistry
D005782:Gels; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam