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Multivariate Optimization of Formulation Variables Influencing Flurbiprofen Proniosomes Characteristics
Faculty
Pharmacy
Year:
2011
Type of Publication:
Article
Pages:
2212-2221
Authors:
Zidan, Ahmed S, Mokhtar, Mahmoud
DOI:
10.1002/jps.22453
Journal:
JOURNAL OF PHARMACEUTICAL SCIENCES WILEY-BLACKWELL
Volume:
100
Research Area:
Pharmacology \& Pharmacy; Chemistry
ISSN
ISI:000289442200018
Keywords :
membrane transport, factorial design, gels, percutaneous, surfactants
Abstract:
Flurbiprofen was formulated as a proniosomal transdermal gel with high drug loading (55.4\%, w/w), using a series of nonionic surfactant and cholesterol. A two-factor, three-level randomized full factorial strategy was developed to optimize simultaneously the effect of surfactant fatty acid side chain length and the amount of cholesterol on the properties of the proniosomes, namely drug permeation characteristics such as steady-state transdermal flux (SSTF), permeability coefficient (PC), and drug entrapment efficiency. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables that showed significant effects on the selected responses. Polynomial equations fitted to the data were used to predict the responses in the optimal region. For maximizing the selected responses using a generalized desirability function, an optimum formulation was found to have a maximum side chain length and minimum cholesterol content. Optimized formulation showed highest entrapment of 39.45\%, percentages drug permeated through cellulose ester membrane of 3.1 and 28.93 after 0.5 and 8 h, respectively, and SSTF and PC of 152 mu g/cm(2) h and 0.263 cm/h, respectively, through rabbit skin. These results demonstrated the efficacy of statistical experimental design to unveil the critical formulation interactions and variability affecting the performance of proniosomal formulations. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2212-2221, 2011
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