Characterization of Ibuprofen nanosuspensions obtained by high pressure homogenization: particle size and dissolution rate

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

Rosario

Congreso; 2° Reunión Internacional de Ciencias Farmacéuticas RICiFa; 2012

Universidad Nacional de Rosario - Universidad Nacional de Córdoba

INTRODUCTION: The Biopharmaceutical Classification System (BCS) presents a systematic organization of drugs based on both solubility and permeability. For instance, Ibuprofen (IBU), a common non-steroidal and anti-inflammatory drug, belongs to class II, i.e., permeate membranes but is poorly soluble in water. The dissolution rate remains one of the most challenging aspects in formulation development and bioavailability of low solubility drugs. 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 purposes of the present study were to develop IBU nanosuspensions (NSs) by high pressure homogenization (HPH), characterize them in terms of particle size, and compare their dissolution rate with IBU powder itself. MATERIALS AND METHODS: Reagents and samples: IBU (pharmaceutical grade, Unifarm, Argentina), hidroxypropylmethylcelullose (BASF, Germany) and distilled water were used for the preparation of NSs via HPH. Two samples of IBU powder, with different particle size (425-600 μm and 250-300 μm), were obtained by sieving. Methods: IBU NSs were obtained using a high pressure homogenizator (Avestin Emulsiflex-C5) at 1500 bar and 30 cycles of homogenization. Particle size analysis was carried out using a zetasizer (Malvern Nano ZS90). Dissolution profiles were performed on apparatus 2 (Erweka DT60), at 50rpm, using 900mL of phosphate buffer solution (pH 7.2) at 37 ± 0.5 ºC. Samples (5 mL) were withdrawn at 5, 10, 20, 30, 45, and 60 minutes with replacement of fresh medium, filtered through 0.45 µm membrane filters, and suitably diluted. Drug concentration was determined spectrophotometrically (Varian Cary 50Conc). Dissolution profiles were statistically analyzed by one-way analysis of variance in terms of Dissolution Efficiency (DE), and the dissolution rate was evaluated throughout mathematical models fitting. RESULTS: The mean diameter size of the NSs obtained was 652.6 nm with a polidispersity index (PDI) of about 0.248. Different dissolution profiles were recorded for NSs and IBU powders, and showed statistically significant differences in terms of dissolution rate and DE. DISCUSSION/CONCLUSION: The HPH is successfully applied to the preparation of Ibuprofen NSs. The improved formulation shows adequate particle size and PDI, and enhanced dissolution rate. Further studies should be conducted in order to fulfill the physicochemical characterization, and evaluate the physical stability of the obtained NSs and the effectiveness of other potentially stabilizer mixtures. ACKNOWLEDGMENTS: W. Starkloff is a doctoral fellowship holder of Universidad Nacional del Sur.