Microwave Assisted Accelerated Stability Study of Amlodipine Besylate in Solid State

Abstract

Stability studies are important to ensure drug product stability and quality until the time of consumption by patients. Real-time stability studies are time-consuming and therefore accelerated stability studies are performed at elevated temperature and humidity conditions to enhance the rate of reaction. According to the International Conference on Harmonisation (ICH) guidelines, accelerated stability studies are performed at 40ºC ± 75 % relative humidity (RH) for 6 months. The microwave-assisted heating has been used in synthetic chemistry for many years to increase the rate of reaction reducing the synthesis time. The use of a microwave to carry out accelerated stability studies rather than the conventional method may reduce the time for predicting the stability of the drug product. However, there is a lack of any substantial evidence about the use of microwave-assisted stability studies in the literature. Hence, the aim of the present work was to evaluate the feasibility of the microwave assisted heating technique in the prediction of drug stability. In the present work, an attempt was made to carry out accelerated stability study of amlodipine besylate (AMD) using microwave heating and conventional method. The degradation profiles from both the methods were compared to correlate the results. The AMD samples were charged in the stability chamber at 40ºC ± 75 % RH and were collected at pre-defined time intervals i.e. 0,1,2,3,4,5 and 6 months. Similarly, samples were also kept in microwave synthesizer at different conditions i.e. power ranging from 200 W to 600 W; temperature ranging from 100 ˚C to 160 ˚C and water content ranging from 50μl to 80 μl. The drug degradation behaviour was determined using high-performance liquid chromatography. The chromatographic profiles obtained from microwave-assisted technique was then compared to the conventional method. The study demonstrated a substantial correlation between conventional and microwave assisted stability. The microwave-assisted stability study under conditions with (50μL water; 400W; 160T; 15min) showed total 6 common degradation product in mixture with glucose to that of the conventional method. Similarly, microwave-assisted stability study under conditions with (50μL water; 200W; 160T; 15min) showed 3 common degradation product in mixture with lactose and (80μL water; 400W; 100T; 15min) showed 3 common degradation product in the tablet as compared to the conventional method. Therefore, to conclude, microwave-assisted heating is an efficient way to perform the accelerated stability study of APIs and formulations.