Microwave-Assited Degradation Studies of Pharmaceuticals

Abstract

“Use of microwave instruments can shorten the drug research time frame significantly” -C. O. Kappe Stress testing as an important segment in the process of getting a drug to the market and is intended to reveal the stability related issues. In stress testing, it is mentioned to perform the task (hydrolytic or thermolytic degradation) at elevated temperature as and when required. Elevation in temperature by means of microwave irradiation has picked up a lot of consideration owing to the in-core heating of the medium. But at the same time it is essential to monitor and optimize parameters of microwave irradiation otherwise there are chances of a false interpretation of the results. An attempt has been made here to compare degradation profile of drug obtained by conventional heating and microwave heating. A hydrolytic degradation study of active pharmaceutical ingredients (APIs) was compared using conventional and microwave-assisted heating techniques. Where acid hydrolytic degradation profile of Alprazolam, Atomoxetine, Repaglinide, Furosemide, Olmesartan, and Hydrochlorothiazide; alkali hydrolytic degradation profile of Escitalopram, Paliperidone, Risperidone, Lurasidone, Olmesartan, and Hydrochlorothiazide; and neutral hydrolytic degradation profile of Hydrochlorothiazide were generated. Microwave conditions were optimized to achieve approximately similar percentage of degradation as obtained by conventional heating technique. Using both the methods, same number of degradation products were generated in each analysed drug. No alteration in the degradation profile was observed for any drug in microwave-assisted degradation study compared to conventional degradation study. However, with the help of microwave heating, reaction time scale is drastically reduced from hours to minutes due to enhanced reaction rate. Hydrolytic degradation of marketed Tablet formulations of Buspirone and Lamotrigine was also carried out using microwave radiation induced heating. There was no alteration in the degradation profile of formulations when compared with the conventional hydrolytic degradation. The degradation reaction time-scale was reduced from 120 min to 40 min in case of BUSP and for LAMO in 2 hr instead of 10 hr. For early prediction of accelerated stability, microwave heating was also used for Tablet formulations of Ramipril and Montelukast (chewable); and Capsule formulation of Bromocriptine Mesylate. The formulations were exposed to microwave radiation at various reaction temperature and heating times with 20% v/w of de-ionised water. The same percentage of impurities were generated in Ramipril and Montelukast formulations by microwave heating, performed at elevated temperature 60-80°C in around 20-60min. However, in Bromocriptine Capsule formulation, different degradation profile was observed. Though the number and types of generated impurities were same, one impurity (bromocriptinine) crossed the acceptance criteria limit (not more than 0.75%) when microwave heating was used at 80°C for 30min. It might be the reason that in conventional accelerated stability study at 40°C/ 75% RH for 3month, intact Capsules were stored. While in microwave-assisted conditions, Capsule powder was directly exposed without Capsule shell. Activation energy for microwave-assisted accelerated testing was calculated for all selected formulations and it was found in the range of 9-11Kcal/mol Therefore, it can be concluded that microwave-assisted heating can be used efficiently to carry out forced degradation study of APIs and formulations. As well as it can be extended to use microwave as a tool to predict accelerated stability study of formulations in pharmaceutical industry with reduced time frame.