Stability-Indicating Analytical Method Development Using Quality by Design (QbD) Approach for Simultaneous Estimation of Budesonide and Levosalbutamol.

Abstract

Budesonide is a corticosteroid; levosalbutamol is bronchodilator. In combination, they are used in the treatment of asthma and chronic obstructive pulmonary disease. The present article portrays the development of a stability-indicating high-performance thin-layer chromatography (HPTLC) method for the simultaneous estimation of budesonide and levosalbutamol using design of experiment (DOE) principles. DOE was applied in development part in which a Box-Behnken design was used to study the effect of factors on the Rf value of the drugs. Twenty-five experimental runs were performed to optimize the chromatographic conditions. Aluminum sheets precoated with silica gel 60 F254 were used as the stationary phase. The optimized mobile phase composition was found to be toluene-ethyl acetate-methanol-ammonia (4:1.8:1.8:0.2) and saturation time 20 min, quantified by densitometric analysis at 231 nm. Moreover, the drugs were subjected to acid and alkali hydrolysis, oxidation, thermal, and photodegradation. The drugs undergo degradation under mainly acidic and basic conditions. Also, the degraded products were well resolved from the pure drug with significantly different Rf values. Linearity was performed in the ranges of 224-1120 ng/band for budesonide and 280-1400 ng/band for levosalbutamol. The method was validated according to the International Conference on Harmonization guidelines. This approach is useful to expedite method development and optimization activities in analytical laboratories. The experimental data revealed that the volume of toluene and methanol in the mobile phase significantly affected the Rf value of both the drugs, and ammonia significantly affected the Rf value of levosalbutamol.