Box-Behnken Design Assisted Optimization and Standardization of Chromatographic Methodology for Quality Assessment of Metformin: Analytical Quality by Design Avenue

Abstract

Background: Metformin (MET) is an oral antidiabetic agent falls chemically under the category of biguanides and it is effectively utilized in the management of type 2 diabetes mellitus. It is marketed in the tablet dosage form and hence quality control and assessment of MET is very much essential and important. Objectives: The objectives of present research investigation are to implement the Box-Behnken Design (BBD) in the optimization and validation of Reverse Phase-High Performance Liquid Chromatographic (RP-HPLC) method for the quality assessment of MET and also to systematically apply the Analytical Quality by Design (AQbD) Approach. Materials and Methods: In methodology BBD was employed to identify and optimize the critical method aspects for augmenting the performance of proposed methodology. The optimum chromatographic elution was performed on Agilent C 18 (5µm, 250 × 4.6 mm i.d.) column employing methanol and 0.1% ortho phosphoric acid in water with pH 2.8 in the proportions of 4:96 v/v as solvent system. The elution was carried out at 0.7 mL/min flow of mobile phase and identification at 231 nm using UV detector. The BBD driven optimized method was standardized as per guidelines of International Council for Harmonisation Q2 (R 1 ) in terms of validating method parameters such as specificity, linearity, detection and quantitation limit, precision, robustness, ruggedness and accuracy. Results: The method was linear in the concentration of 5-25µg/ml with R 2 = 0.999. The detection and quantitation limit were obtained at concentration of 0.30 and 0.93 µg /ml. The values of precision, robustness, and ruggedness parameters were found to be well within the required limit of acceptance with deviation of relative standard < 2%. The accuracy of MET was observed 99.22% to 100.25% at three different recovery experiments. At the end the proposed design of experiment (DoE) oriented methodology successfully applied for quantification of MET. Conclusion: The BBD and AQbD approaches are highly useful for the quality assessment of MET in bulk and its marketed tablet dosage forms.

Marker Based Standardization of Quercetin in Marketed Capsules by Novel Zero Order Spectroscopic and Area Under Curve Spectroscopic Methods

“…The UV-spectrophotometer Shimadzu 1800 (Figure 2) was used for analysis of Quercetin. [52][53][54][55][56][57] UV-spectrophotometer (Shimadzu 1800)…”

“…The developed UV-spectrophotometric method was validated as per ICH guidelines in terms of specificity, selectivity, linearity, LOD, LOQ, precision, ruggedness and accuracy. [55][56][57][58][59][60]…”

Exploring Analytical Quality by Design (AQbD) Enabled RP-HPLC Method for Carvedilol

“…Further these agencies are emphasizing the use of Analytical Quality by Design (AQbD) approach for development of analytical method. 1 Initially Quality by Design (QbD) approach was utilized by formulation scientists to imbibe the quality in the product during its development stage itself. Further the need of accurate and precise analytical method faced by industry explored its use in analytical method development and flourished as AQbD approach.…”

Quality assessment of metformin hydrochloride tablets retailed in Lagos, Nigeria

“…The quality assessment of drugs and their pharmaceutical formulations is very important and essential during the product development stage in the pharmaceutical industry. Analytical assessment is the critical approach to quality control of pharmaceutical products (Suryawanshi & Palled, 2022). With the growth in pharmaceutical industries, the number of pharmaceutical products (branded as well as generic) is increasing in the market so maintaining its quality is the primary concern for manufacturers (Kalo et.…”