Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Metformin Hydrochloride in Tablet Dosage Forms by HPLC
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/6/1187 |
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| author | Mousa Sha’at Adrian Florin Spac Iulian Stoleriu Alexandra Bujor Monica Stamate Cretan Mihaela Hartan Lacramioara Ochiuz |
| author_facet | Mousa Sha’at Adrian Florin Spac Iulian Stoleriu Alexandra Bujor Monica Stamate Cretan Mihaela Hartan Lacramioara Ochiuz |
| author_sort | Mousa Sha’at |
| collection | DOAJ |
| description | 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 (<i>v</i>/<i>v</i>) as the mobile phase with a flow rate 1 mL/min. The separation was made on a Thermoscientific ODS Hypersyl<sup>TM</sup> 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. |
| first_indexed | 2024-03-09T22:45:40Z |
| format | Article |
| id | doaj.art-9d1397731e5f43e6abb250b1ff834f02 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:45:40Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-9d1397731e5f43e6abb250b1ff834f022023-11-23T18:29:40ZengMDPI AGPharmaceutics1999-49232022-05-01146118710.3390/pharmaceutics14061187Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Metformin Hydrochloride in Tablet Dosage Forms by HPLCMousa Sha’at0Adrian Florin Spac1Iulian Stoleriu2Alexandra Bujor3Monica Stamate Cretan4Mihaela Hartan5Lacramioara Ochiuz6Department of Pharmaceutical Technology, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iași, RomaniaDepartment of Phisico-Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iași, RomaniaFaculty of Mathematics, “Al. I. Cuza” University, 11, Blvd. Carol the 1st, 700506 Iași, RomaniaDepartment of Pharmaceutical Technology, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iași, RomaniaDepartment of Pharmaceutical Technology, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iași, RomaniaRegional Institute of Oncology, 2-4 General Henri Mathias Berthelot Street, 700483 Iași, RomaniaDepartment of Pharmaceutical Technology, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iași, RomaniaThe 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 (<i>v</i>/<i>v</i>) as the mobile phase with a flow rate 1 mL/min. The separation was made on a Thermoscientific ODS Hypersyl<sup>TM</sup> 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.https://www.mdpi.com/1999-4923/14/6/1187metformin hydrochloridequality by design (QbD)central composite design (CCD)critical analytical attributes (CAA)HPLCvalidation |
| spellingShingle | Mousa Sha’at Adrian Florin Spac Iulian Stoleriu Alexandra Bujor Monica Stamate Cretan Mihaela Hartan Lacramioara Ochiuz Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Metformin Hydrochloride in Tablet Dosage Forms by HPLC Pharmaceutics metformin hydrochloride quality by design (QbD) central composite design (CCD) critical analytical attributes (CAA) HPLC validation |
| title | Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Metformin Hydrochloride in Tablet Dosage Forms by HPLC |
| title_full | Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Metformin Hydrochloride in Tablet Dosage Forms by HPLC |
| title_fullStr | Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Metformin Hydrochloride in Tablet Dosage Forms by HPLC |
| title_full_unstemmed | Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Metformin Hydrochloride in Tablet Dosage Forms by HPLC |
| title_short | Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Metformin Hydrochloride in Tablet Dosage Forms by HPLC |
| title_sort | implementation of qbd approach to the analytical method development and validation for the estimation of metformin hydrochloride in tablet dosage forms by hplc |
| topic | metformin hydrochloride quality by design (QbD) central composite design (CCD) critical analytical attributes (CAA) HPLC validation |
| url | https://www.mdpi.com/1999-4923/14/6/1187 |
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