Capecitabine is an anti-metabolite class of anti-neoplastic drug that is converted to fluorouracil in body tissue. Numbers of stability indicating chromatography method such as HPLC, HPTLC etc.have been reported for stability study of capecitabine. But the chromatography methods are tedious, time and solvent consuming methods. Hence, stability-indicating UV-visible spectroscopy method has been developed for hydrolytic degradation kinetic study of capecitabine using design of experiments (DoE)-based enhanced quality by design approach (QbD) to save time, solvent and cost of analysis. The potential method parameters were identified and assessed by risk priority number (RPN) ranking and filtering. The DoE-based full factorial designs were applied for degradation kinetic study in alkaline and acidic medium at different temperature. The rate constant, order of reaction, half-life and % degradation of capecitabine was calculated. The absorbencies of all samples were measured at 307nm wavelength and linearity of capecitabine was found to be in the range of 5-25µg/mL. The order of reactions for alkaline and acidic degradation kinetic was found to be first order. The highest degradation rate constant and % degradation of capecitabine was found to be in 0.3 N acid or base at 50˚C. The prediction of rate constant and % degradation of capecitabine was done using DoE-based response surface analysis. The data of degradation kinetic was found to be in good agreement with published RP-HPLC method of capecitabine.

Numerous reversed-phase high-pressure liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) techniques have been published for the estimation of fixed-dose combinations (FDCs) of telmisartan (TEL). No published literature has been reported to date which described the synchronous estimation of FDCs of TEL using a single chromatography condition. Hence, the RP-HPLC method has been developed and validated for synchronous analysis of FDCs of TEL using an enhanced analytical quality by design (AQbD) approach to save time, cost and solvent for analysis. The implementation of AQbD was initiated with the identification of failure modes (FMs) using the Ishikawa diagram, and their critical effect analysis was carried out by risk priority number ranking and filtering method. The identified critical FMs were optimized by design of experiments-based response surface modeling using the Box–Behnken design. The method operable design region was navigated and control strategy was framed to mitigate the risk of critical FM. The RP-HPLC method was developed using Shim-Pack octadecyl silane C18 column and acetonitrile: 1.0%v/v triethylamine (pH 6.5 adjusted using perchloric acid; 42:58, %v/v). The developed method was found to be validated as per the International Council For Harmonization Q2 (R1) guideline. The method was applied for the synchronous assay of seven different FDCs of TEL and assay results were found in good compliance with the respective labeled claim.

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Telmisartan is an antihypertensive drug and several FDC products of telmisartan are available in the market for the treatment of hypertension. The multipurpose reverse-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated as economical and eco-friendly alternative to numerous published chromatography methods for synchronous estimation of FDC of telmisartan to save time, cost and solvent for analysis. The analytical quality risk management was initiated with identification of potential method parameters using cause–effect diagram followed by assessment of their risk by risk priority number ranking and filtering method. The risk of critical method parameters was controlled by their optimization using design of experiments-based full-factorial design. The method operable design ranges was identified for high-risk method parameters, and control strategy was set for mitigation of their risk throughout the life cycle of the developed RP-HPLC method. The RP-HPLC method was validated as per the ICH Q2 (R1) guideline. The RP-HPLC method was applied for simultaneous estimation of seven FDC products of telmisartan, and results were found compliance with labeled claim. The developed RP-HPLC method is fulfilling requirements of numerous RP-HPLC and high performance thin layer chromatography methods for the said estimation. It can be used as a multipurpose RP-HPLC method for quality control of FDC products of telmisartan in the pharmaceutical industry to save solvent, cost and time of analysis.