Albendazole nanosuspensions obtained by bottom-up methodology: Preliminary studies

STARKLOFF, W. J.; GONZALEZ VIDAL, N. L.; ALLEMANDI, D. A.; PALMA, S. D.

Rosario

Congreso; 2da. Reunión Internacional de Ciencias Farmacéuticas RICiFa; 2012

Universidad Nacional de Rosario - Universidad Nacional de C¨®rdoba

INTRODUCTION: Helminth infections are a major health problem mainly in developing countries. Albendazole (ABZ) is the most effective broad-spectrum antihelmintic agent. The biggest problem of this drug is its low aqueous solubility, which lead to an erratic availability and great intra-individual variations in the levels found in different tissues. One of the possibilities for improving dissolution of poorly soluble drugs is to increase the available surface area by decreasing the solid particle size, through top-down or bottom-up methodologies. The aims of the present study were to investigate the feasibility of preparing ABZ nanosuspensions (NSs) by precipitation methodology, characterize them in terms of particle size, assay, and dissolution rate and compare them with commercial suspensions and ABZ powder itself. MATERIALS AND METHODS: ABZ (pharmaceutical grade, Parafarm, Argentina), hidroxypropylmethylcelullose (BASF, Germany), clorhidric acid (analytic grade, Anedra, Argentina), methilic alcohol (analytic grade, Dorwil, Argentina) and distilled water were used for the formulation of NSs (0.2g/100mL) via nanoprecipitation by antisolvent technique. Two commercial ABZ oral suspensions (A and B, 3.8g/100mL), manufactured by different pharmaceutical companies, were purchased from veterinary shops. Solvent evaporation was carried out using a rotary evaporator (Buchi Rotavapor R-124). Particle size analysis of NSs was carried out using a zetasizer (Malvern Nano ZS90), and a laser diffraction analyzer (Horiba LA950V2) was used for commercial suspension analysis. Drug content was performed according to USP. Dissolution profiles were performed on apparatus 2 (Erweka DT60), at 25rpm, using 900mL of 0.1N HCl solution and the samples were suitably diluted and analyzed spectrophotometrically (Varian Cary 50Conc) at 310 nm. Dissolution profiles were statistically analyzed by one-way analysis of variance in terms of Dissolution Efficiency (DE). The dissolution rate was evaluated throughout mathematical models fitting. RESULTS: The mean diameter size of the NSs obtained was 312.6 nm, with a polidispersity index (PDI) of about 0.377. The median particle size was 8.233 +/- 0.087 um for sample A and 6.781 +/- 0.019 um for sample B. The content of ABZ was 109.42% and 110.75% for commercial suspensions A and B, respectively, and 96.21% for NSs. Statistically significant differences were recorded for dissolution rate and DE of NSs, compared with commercial suspensions and ABZ powder. CONCLUSION: The methodology used is successfully applied to the preparation of ABZ NSs. The NSs obtained show suitable particle size and PDI. The dissolution of ABZ is clearly improved with the formulation of NSs. Further studies should be conducted in order to evaluate the physical stability of the NSs and the possibility of improving particle size and PDI by subsequent high pressure homogenization methodology. ACKNOWLEDGMENTS: W. Starkloff is a doctoral fellowship holder of Universidad Nacional del Sur.