Romanian Society of Pharmaceutical Sciences

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STUDIES ON THE EFFECTS OF INCLUSION COMPLEXATION OF FENOFIBRATE WITH EPI-NS VS. -CD AND SOME OF ITS SUBSTITUTED DERIVATIVES

ANGELA NEDELCU 1, ANDREEA-ALEXANDRA OLTEANU 1*, IOANA CLEMENTINA
COSTANTINESCU 1, MARINELA FLOREA 1, LUCIAN-MIHAI STĂNESCU 1, ŞTEFANIA-
FELICIA BĂRBUCEANU 2, CORINA-CRISTINA ARAMĂ 1

1 Analytical Chemistry Department, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy Bucharest, 6 Traian Vuia Street, 020956, Bucharest, Romania
2 Organic Chemistry Department, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy Bucharest, 6 Traian Vuia Street, 020956, Bucharest, Romania

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Fenofibrate is a derivative of fibric acid that acts as a peroxisome proliferator-activated receptor alpha (PPAR-) agonist. Beside the lowering effect on serum level of triglycerides and low-density lipoprotein (LDL) which makes it a therapeutic agent for hypertriglyceridemia and dyslipidaemia, it has anti-inflammatory, antioxidant and antiangiogenic effect. Fenofibrate is a class II BCS drug with a poor water solubility (less than 0.5 mg/L) and high lipophilicity (log P = 5.2) and has low oral bioavailability. The objectives of this study are to characterize the interaction between fenofibrate and -cyclodextrin or some of its substituted derivatives or -cyclodextrin based nanosponges (EPI-NS) and the effect of the complexation on fenofibrate solubility, with the aim of developing a new therapeutic entity. EPI-NS were prepared and characterized by FT-IR spectra and thermal analysis. The inclusion complexes between FEN and -CD, RAMEB, Captisol or EPI-NS were prepared both by lyophilisation and wet kneading (using dichloro-methane, DCM) and characterized by FT-IR, and thermal analysis. Solubility studies were performed according to the method reported by Higuchi and Connors and the phase solubility diagrams were plotted. The complexation of FEN with CDs and EPI-NS was confirmed. FEN water solubility is significantly enhanced by inclusion in CDs cavities. RAMEB has the highest effect, but FEN-CAPTISOL complex is the most stable (Kapp = 1239 M-1). EPI-NS improves consistently FEN solubility, around 40 times the intrinsic solubility.