Solid dispersions. A tool to improve the dissolution rate of Oxfendazole

SÁNCHEZ BRUNI, SERGIO; ARDUSSO MARINA S; PALMA SANTIAGO D; ALLEMANDI DANIEL A

Mar del Plata

Congreso; XLVIII Reunión anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

SAFE

INTRODUCTION: Parasitism is a disease that may affect men and pets as well. Treating this disease, Anthelmintics benzimidazoles (BZD) have achieved a therapeutic significance due to their characteristics of broad spectrum, low toxicity and low cost. The formulation, bioavailability and efficacy of BZD anthelmintics are limited by the low gastrointestinal absorption and lack of aqueous solubility. To confront this, several technological methods have been reported for the improvement of drug solubility and dissolution rate. Such an approach, with significant advantages, is the formulation of hydrophobic drugs in high-energy amorphous forms, such as solid dispersions (SDs). Our hypothesis is to increase the rate of dissolution oxfendazole (OFZ) incorporating it in SDs as a strategy to improve bioavailability. OBJECTIVE: Prepare and evaluate physicochemical and biopharmaceutical properties of SDs using poloxamer 188 (PXM) as carrier of OFZ. METHODS: SDs were prepared by melting of OFZ and PXM. The systems were characterized by XRP Diffraction, Scanning Electron Microscopy (SEM), solubility studies, and dissolution tests. RESULTS: No interactions between the components of SDs were observed in XRD diffractograms. The SEM of SD observed irregular particles where it is not possible to differentiate the OFZ from PXM. While in physical mixture, the OFZ can be seen spread over the carrier surface. The solubility indicates that if PXM presence is up to 1% w/v then OFZ solubility in HCI 0.1 N is not altered. In addition, 50 and 200 mg (OFZ) SDs dissolution profiles at time = 15min showed an increased rate of 12.4 and 12.8 respectively, compared to the same dose of OFZ. Whereas applying the F1 difference factor to the corresponding 10 and 50 mg SDs profiles, it determined a curve overlapping. This increase in dissolution rate may be due to the presence of PXM that improves the particles wettability. CONCLUSIONS: In every evaluated dose, a remarkable increase in OFZ dissolution rate in SDs is achieved in comparison to OFZ.Keywords: Solid Dispersion; Poloxamer; Oxfendazole; Dissolution