OB JECTIV E S

1. Structural and in-vitro release evaluations of poloxamer gel containing metal-oxicam coordination compounds Ana AndreeaStănescu1, Adina Cimpoieșu2, Adrian A. Andrieș3, Sultana Niță4, Dalia SimonaMiron5, Flavian StefanRadulescu3 University of Medicine and Pharmacy „Carol Davila” Bucharest, 1Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, 6, Traian Vuia Street, 020956, Bucharest, Romania. 2Faculty of Pharmacy, Department of Drug Control, 6, Traian Vuia Street, 020956, Bucharest, Romania. 3Faculty of Pharmacy, Department of Drug Industry and Pharmaceutical Biotechnologies, 6, Traian Vuia Street, 020956, Bucharest, Romania. 4National Institute for Chemical Pharmaceutical Research and Development, 112 Calea Vitan, 031299, Bucharest, Romania. 5Faculty of Medicine, Department of Pharmaceutical Physics and Informatics, 6, Traian Vuia Street, 020956, Bucharest, Romania. Corresponding author: aastanescu@yahoo.com OBJECTIVES The aim was to develop and adequately characterize, through structural analaysis and in-vitro drug release evaluations, new topical semisolid hydrophilic gels, used for administration of organometalic complexes on skin and mucosa. MATERIALS AND METHODS The first stage was focused on the design of the vehicle and selection of a manufacturing procedure, able to generate a molecular dispersion of the hydrophobic active ingredient (noted Cx1 and Cx2, differening in the type of organic ligand). A hydrophilic polyoxyethylene-polyoxypropylene block copolymers matrix (micronized poloxamer 407, BASF GmbH) was selected, based on the its remarkable biocompatibility. A minimum quantity of cosolvent mixture was added, 10% ethanol absolute and 5% nonionic tensioactive or standardized mixture of surfactants, isopropyl-myristate (F1); Cremophor EL (F2); Saboderm G20 (F3) and Saboderm SHO (F4). The thermosensitive hydrogels were analyzed by a set of correlated tests, including the analysis of the rheological behavior (hysteresis loop test, [1]) and the evaluation of in-vitro release profiles using a vertical diffusion cell system[2]. RESULTS AND DISCUSSION The hysteresis loop test indicated a pseudoplastic character, demonstrated by the applicability of the Ostwald de Waele model and by the values of the flow behavior index lower than 1. The in-vitro release rates were unexpectedly high (in some instances, higher than 1 µg/cm2/min1/2), with an apparent dependence on the physico-chemical properties of the complex. Figure 3. Figure 4. Figure 1. Figure 2. Figure 5. Figure 6. Table 1. Parameters of the Higuchi model applied to in-vitro release profile of Cx1 Table 2. Parameters of the Higuchi model applied to in-vitro release profile of Cx2 CONCLUSIONS The hydrophilic semisolid formulations developed based on polyoxyethylene-polyoxypropylene block copolymers showed adequate properties as vehicles for the hydrophobic organometalic complexes. They displayed pseudoplastic behavior, and in-vitro release profiles highly dependent on the solubility within the semisolid matrix. ACKNOWLEDGEMENT REFERENCES This work was supported by the Romanian Partnership Programme PN II - supported by the National Agency for Scientific Research - ANCS, CNDI - UEFISCDI, contract number 126/2012. [1]Lee CH, Moturi V, Lee Y.Thixotropic property in pharmaceutical formulations.J Control Release. 2009;136(2):88-98. [2] United States Pharmacopoeia 36 - National Formulary 31, First supplement. Chapter <1724>.