Romanian Society of Pharmaceutical Sciences
 

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PREFORMULATION STUDIES USING COSOLVENT SYSTEMS TO INCREASE THE SOLUBILITY OF A NEW ENROFLOXACIN RUTHENIUM (III) COMPLEX WITH BIOLOGICAL ACTIVITY

VALENTINA UIVAROSI1, CRISTINA DINU PÎRVU2*, MIHAELA VIOLETA GHICA2, VALENTINA ANUŢA2

1Department of General and Inorganic Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia,
2Department of Physical and Colloidal Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania

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Enhancement of solubility, dissolution rate and bioavailability of poorly water soluble new chemical entities is a very challenging task in pharmaceutical formulation development. Present study explores different technological approaches to enhance the solubility of a novel complex Ru(III)-enrofloxacin by using various co-solvent systems. Preliminary tests using water:dioxane co-solvent systems were used for optimizing the solubilization process and for determining the dielectric requirement value (DR). Dioxane was then substituted with the most frequently used low-toxicity co-solvents for pharmaceutical use: polypropylene glycol, polyethylene glycol 400, glycerol and ethanol, mixed in volume ratios so that the DR to be respected. The complex solubility was increased to roughly 1 mg/mL by using binary and ternary biocompatible co-solvent systems with apparent dielectic constant of 64.61, comparing to the water solubility of 0.034mg/mL. The release kinetics from saturated solutions prepared in biocompatible cosolvent systems was evaluated for 6 hours, by using a modified Franz diffusion cell fitted with a regenerated cellulose membrane. The obtained release kinetic data were best fitted by means of Higuchi model, suggesting a diffusion-based release mechanism.