Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Metformin Hydrochloride in Tablet Dosage Forms by HPLC

Abstract

The current studies entail quality by design (QbD)-enabled development of a simple, rapid, precise, accurate, and cost-effective high-performance liquid chromatographic method for estimation of metformin hydrochloride (M-HCl). Design of experiments (DoE) was applied for multivariate optimization of the experimental conditions of the HPLC method. Risk assessment was performed to identify the critical method parameters (CMPs) using Ishikawa diagram. The factor screening studies were performed using a two-factor three-levels design. Two independent factors, buffer pH and mobile phase composition, were used to design mathematical models. Central composite design (CCD) was used to study the response surface methodology and to study in depth the effects of these independent factors, thus evaluating the critical analytical attributes (CAAs), namely, retention time, peak area, and symmetry factor as the parameters of method robustness. Desirability function was used to simultaneously optimize the CAAs. The optimized and predicted data from contour diagram consisted of 0.02 M acetate buffer pH = 3/methanol in a ratio of 70/30 (v/v) as the mobile phase with a flow rate 1 mL/min. The separation was made on a Thermoscientific ODS HypersylTM chromatographic column (250 × 4.6 mm, 5 μm) with oven temperature 35 °C and UV detection at 235 nm. The optimized assay conditions were validated according to ICH guidelines. Hence, the results clearly showed that QbD approach could be successfully applied to optimize HPLC method for estimation of M-HCl. The method was applied both for the evaluation of M-HCl content in tablets, and for in vitro dissolution studies of M-HCl from conventional and prolonged-release tablets.

Optimization of chromatographic conditions via Box‒Behnken design in RP-HPLC-PDA method development for the estimation of folic acid and methotrexate in bulk and tablets

“…The following are covered from the literature on QbD application in HPLC method development. Following the next steps, authentic literature search and initial risk assessment, analytical target profile (ATP) identifications, critical method attributes (CMA), risk assessment, and thane method optimization were performed [ 26 , 27 ]. Design Expert software, version 13.0.3.0, was used from Stat-Ease Inc., Minneapolis, USA.…”

Analytical quality by design approach for the development of high‐performance liquid chromatography method for simultaneous analysis of metformin and sitagliptin in the presence of major degradation products

“…The dose ratio of MET to SIT with 10:1 is one of the challenges for an analyst in developing a robust analytical method using the high-performance liquid chromatography (HPLC) technique. Nevertheless, analytical methods have been reported for simultaneous assay of MET and SIT using HPLC [4][5][6][7][8][9][10], and bio-analytical LC-mass spectrometry (LC-MS) [11,12] studies. From the reported HPLC methods, it was inferred that retention of MET on the C 18 column is very poor and causes the co-elution of impurities, even at column void.…”

“…In this context, in a literature search on robust analytics, Hendy et al [6] reported an ultra-HPLC (UHPLC) method using the design of experiment (DoE) approach, but the study was not designed on the separation of impurities. Shat et al [7] employed quality by design (QbD) to determine MET in tablet dosage form, but not intended for simultaneous analysis [8]. Overall, there are no reports available on the QbD-based robust HPLC method for simultaneous assay of MET/SIT in the presence of their co-eluting impurities.…”

“…Shat et al. [7] employed quality by design (QbD) to determine MET in tablet dosage form, but not intended for simultaneous analysis [8]. Overall, there are no reports available on the QbD‐based robust HPLC method for simultaneous assay of MET/SIT in the presence of their co‐eluting impurities.…”

New Ion Selective Electrodes for Analysis of Metformin Based on Molecularly Imprinted Polymers

“…The functional monomer model can be accommodated by the cross-linkers and the monomer's chemical connections. After polymerization, the template can be removed, revealing binding sites with new forms, sizes, and chemical characteristics [8][9][10][11]. A biguanide antihyperglycemic drug is metformin.…”