Influence of UV-wavelength and sensitivity on the investigation of Ibuprofen biowaivers

GONZALEZ VIDAL, N. L.; GIL ALEGRE, M. E.

Rosario

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

Universidad Nacional de Rosario - Universidad Nacional de Córdoba

INTRODUCTION: The Biopharmaceutics Classification System allows waivers of bioequivalence studies for IR oral dosage forms containing Class I drugs. Further discussions recommended that biowaiver can be extended to Class II weak acids, such as Ibuprofen (IBU). The sensitivity of the analytical method is relevant, since an average difference of no more than 10% between dissolution profiles may be acceptable for similarity determination. The dissolution test for IBU tablets applies quantification at about 221nm; meanwhile identification should be carried out at about 264 and 272/273nm. Investigation on the possibility of IBU biowaivers was carried out using Ph. Eur. identification wavelength (264nm).The purpose of the present study was to evaluate the sensitivity of UV measurements, at different wavelengths, and verify the suitability of the analytical method for IBU biowaiver studies. MATERIALS AND METHODS: Reagents: IBU Ph. Eur. bulk drug, 99.8% purity and 0.1% humidity (Guinama, Spain). Buffer solutions pH 1.2, 4.5 and 6.8 were used. The maximum concentration (mg/mL) of dissolved IBU was 0.02 (pH 1.2), 0.03 (pH 4.5) and 0.5 (pH 6.8), corresponding to 120% of test concentration. Successive dilutions were made for linearity solutions. Methods: Linearity was determined in triplicate (Shimadzu UV-1700 PharmaSpec) and statistically evaluated using Statgraphics Plus (v.5.1). The sensitivity was evaluated through the slope of the calibration curve and the discriminant capacity. RESULTS: Linear regression method was highly significant. For gastric pH, the slopes at 264/272nm were reduced 20-fold with respect to those at 221nm. At pH 4.5, all slopes doubled the ones obtained at pH 1.2, and a 20-fold reduction in slope value is also produced at 264/272nm. At jejunum pH, the slope almost duplicated the one obtained at pH 4.5, with also a large difference between wavelenghts (Table 1). A 10% difference between analyte concentrations could be recorded only at 221nm, for all pHs. This level of discrimination is needed to obtain a similarity factor of 50. The UV method at 264nm for pH 1.2 was not able to detect such 10% differences (discriminant capacity ~ 24%). DISCUSSION / CONCLUSION: The highest calibration sensitivity is obtained at 221nm, at the three pHs. At 264/272nm, the UV-method is not sensitive enough to detect the 10% difference required for f2, especially at acidic pHs. According to these results, the measurements for IBU biowaiver might be carried out at 221nm, in order to get suitable discrimation between profiles. ACKNOWLEDGMENTS: Ministerio de Educación (Argentine) - Fundación Carolina