Patient-Centric Design in Orodispersible Films: Balancing Efficacy and Acceptability

This chapter describes a simple, sensitive, and cost-effective mobile phase method for determination and quantitation of diastereomeric impurities of Entecavir in drug substances and drug products. Effective chromatographic separation was achieved on a C18 stationary phase (150 x 4.6 mm, 3.5 microns particles) with the economical and simple mobile phase combination such as water and acetonitrile in the ratio of 95:5 (% v/v) delivered in an isocratic mode at a flow rate of 1.0 mL/min at 254 nm. In the developed method, the resolution between Entecavir and its diastereomeric impurities were found to be greater than 2.0. The linearity of the method was demonstrated by means of correlation Co-efficient square (r2) value for Entecavir and its diastereomeric impurities were found to be greater than 0.999. The limit of detection for imp-1, imp-2, imp-3 and Entecavir were 0.002%, 0.002%, 0.003% and 0.008% and the limit of quantification for imp-1, imp-2, imp-3 and Entecavir were 0.007%, 0.006%, 0.008% and 0.025% respectively. The %recovery for imp-1, imp-2, imp-3 were observed in the range between 95 and 105%. The test solution was found to be stable in the diluent for 48 h. The drug was subjected to stress conditions. The mass balance was found close to 99.5%.