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Velichka Andonova,1,2 Petya Peneva,1,2 George S Georgiev,3 Vencislava T Toncheva,3 Elisaveta Apostolova,4 Zhivko Peychev,5 Stela Dimitrova,6 Mariana Katsarova,6 Nadia Petrova,7 Margarita Kassarova1,2 1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Medical University-Plovdiv, 2Technological Center for Emergency Medicine (TCEMED), Plovdiv, 3Faculty of Chemistry and Pharmacy, Sofia University “St Kliment Ohridski”, Sofia, 4Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University-Plovdiv, 5Department of Medical Informatics, Biostatistics and e-learning, Faculty of Public Health, Medical University-Plovdiv, 6Department of Chemistry and Biochemistry, Faculty of Pharmacy, Medical University-Plovdiv, Plovdiv, 7Institute of Mineralogy and Crystallography, Bulgarian Academy of Sciences, Sofia, Bulgaria Abstract: The purpose of the study was to investigate the stability and biopharmaceutical characteristics of ketoprofen, loaded in polymeric carriers, which were included into a bigel in a semisolid dosage form. The polymer carriers with in situ-included ketoprofen were obtained by emulsifier-free emulsion polymerization of the monomers in aqueous medium or a solution of the polymers used. The morphological characteristics of the carriers, the in vitro release and the photochemical stability of ketoprofen were evaluated. The model with optimal characteristics was included in a bigel formulation. The bigel was characterized in terms of pH, rheological behavior, spreadability, and in vitro drug release. Acute skin toxicity, antinociceptive activity, anti-inflammatory activity, and antihyperalgesic effects of the prepared bigel with ketoprofen-loaded polymer carrier were evaluated. The carriers of ketoprofen were characterized by a high yield and drug loading. The particle size distribution varied widely according to the polymer used, and a sustained release was provided for up to 6 hours. The polymer mixture poly(vinyl acetate) and hydroxypropyl cellulose as a drug carrier, alone or included in the bigel composition, improved the photostability of the drug compared with unprotected ketoprofen. The bigel with ketoprofen-loaded particles provided sustained release of the drug and had optimal rheological parameters. In vivo experiments on the bigel showed no skin inflammation or irritation. Four hours after its application, a well-defined analgesic, anti-inflammatory, and antihyperalgesic effect was registered. The polymer mixture of poly(vinyl acetate) and hydroxypropyl cellulose as a carrier of ketoprofen and the bigel in which it was included provided an enhanced photostability and sustained drug release. Keywords: antihyperalgesic effect, antinociceptive activity, biphasic systems, carrageenan-induced edema, emulsifier-free radical polymerization |
