Screening Design and Response Surface Methodology for the Simultaneous Estimation of Carvedilol and Ivabradine HCl by HPTLC Method.

Abstract

The combination of carvedilol (CAR) and ivabradine (IVA) is used for a greater reduction in heart rate and for achieving better exercise capacity in a patient with chronic heart failure. Numerous reverse-phase high-pressure liquid chromatography (RP-HPLC) and hyphenated techniques have been reported for the simultaneous estimation of CAR and IVA, but the high-performance thin-layer chromatographic (HPTLC) method has not been reported yet. Hence, the robust HPTLC method has been developed by the implementation of an enhanced analytical quality by design approach based on the principles of analytical failure modes critical effect analysis (AFMCEA) and design of experiments (DoE) as per the upcoming ICH Q14 guideline. The AFMCEA was started by the identification of potential analytical failure modes followed by their critical effect analysis by a DoE-based screening design. The high-risk failure modes were optimized by DoE-based response surface methodology. The method operable design ranges and control strategy was framed for optimized chromatography conditions. The HPTLC method was validated as per ICH Q2 (R1) guideline. The HPTLC method was applied for the assay of FDC of CAR and IVA, and results were found in compliance with the labeled claim. The developed method can be used as an alternative to the published RP-HPLC method for quality control of FDC of CAR and IVA in the pharmaceutical industry.