Microwave-Assisted Hydrolytic Degradation of Sartans Drug with the Application of Quality-by-Design (Qbd) Approach

Abstract

A novel Microwave-assisted forced degradation method was developed for carrying out hydrolytic degradation in acidic and alkaline condition with the help of Box-Behnken design approach. Experimental design has been used during forced degradation to determine significant factors of Microwave responsible for degradation and to obtain optimal degradation conditions. In addition, acid and alkali hydrolysis was performed using a Anton-paar Synthos Microwave Synthesizer. The optimization of method was done with the help of trial approach by application of Box-Behnken design. The parameters selected for this purpose were Power, Temperature and Time for Microwave. The design working space region was identified by the application of Design Expert software to Losartan in acidic condition and the obtained optimized design space was then applied to alkaline condition of Losartan and also to other drugs of same category, i.e Valsartan and Telmisartan in both the conditions. The chromatographic method employed the Column- C-18 Inertsil ODS, 150 x 4.6mm, 5μm particle size with mobile phase consisting of gradient method of Mobile phase A of 0.02%, v/v TFA in water and Mobile phase B of 0.01%, v/v TFA in ACN: Methanol (75:25) with a 30 minutes run time and the detection was performed at 240 nm. The procedure was validated for system suitability, linearity and precision. There was no interference observed of degradation products in the determination of the active pharmaceutical ingredient. The main aim was to achieve degradation in the range of 5- 20% according to the guidelines. By studying the plots of Temperature, Power and Time, it was concluded that the main factor affecting the microwave degradation of drugs was Power and to some extent temperature. The time factor had the least effect on the microwave- assisted degradation of drug. The design space for microwave could be applied for similar drug and similar condition. The method was found to be robust, reproducible in terms of generation of Degradation products for all the three drugs in individual.