Evaluation of physicochemical stability and degradation kinetics of bedaquiline in hydrolytic solutions of different pH

Abstract

Background Tuberculosis is an infection that has high mortality rate in human as well as in animals if it remains unattained for long time. Scientists are always desirous to discover new molecules against Mycobacterium tuberculosis; one of them is bedaquiline which was recently approved to treat multidrug resistance TB. During the clinical study of new molecule stability and impurity are the key aspects to develop formulation. Stability issues in bulk drug are dangerous to drug safety and needs careful attention in formulation development. Bedaquiline stability study was completed with reversed-phase high-performance liquid chromatography (HPLC) and utilized in degradation kinetic study of bedaquiline in aqueous condition under different pH, temperature, and concentrations of degradant. Results Linearity was obtained in 50.0-250.0μg/ml, correlation coefficient, and regression line equation were 0.998 and Y=18528x + 7E+06 respectively. Intraday, inter day precision, and repeatability RSD were less than 2.0%. Average recovery in accuracy study was more than 98.0% showed that good recovery was obtained. Degradation kinetics parameters like activation energy (Ea), half-life (t50), rate constant (k), and shelf life (t90) were calculated under different condition for bedaquiline. Entropy and enthalpy of reaction was studied to gather knowledge about energy of system. Conclusion The result explained that bedaquiline degradation was pH-dependant, as increase in concentration of degradant and temperature, there was increase in degradation rate of bedaquiline. Bedaquiline was stable in neutral aqueous condition and at lower temperatures, shows that drug is hydrophobic in nature. Kinetic data showed that bedaquiline followed first order kinetics in acidic and alkaline pH.

Systematic strategies for degradation kinetic study of pharmaceuticals: an issue of utmost importance concerning current stability analysis practices

“…This advancement in degradation study requires the study of degradation kinetic data to evaluate deviation from normal degradation kinetic of drug substance and drug product. (1984), Lerner et al (1988), Oliveira et al (2013Oliveira et al ( , 2016, Paczkowska et al (2015), Rajput and Vanavi (2021) degradation of pharmaceuticals. The basis of change in chemical kinetics includes the formation of a product that can further increase or decrease the rate of drug degradation reaction.…”

Separation and Characterization of Novel Degradation and Process Related Impurities of Bedaquiline Bulk Drug

“…Literature survey for analytical data of BDQ showed that spectrophotometric method ( 5 ), forced degradation study ( 6 ), simultaneous estimation ( 7 , 8 ), bio-analytical HPLC/MS methods ( 9 , 10 ), chiral analysis ( 11 , 12 ), pharmacokinetic study ( 13 , 14 ) and simultaneous bio-analytical analysis ( 15 ) have been reported till date. The only one reported stability study ( 6 ) does not report the identification of DPs or process related impurities of BDQ.…”