Elimination of the Ultraviolet Spectrophotometric-Based Limitation on the Quantification of Metformin HCl in Acid-Stage Medium for a Comparative Dissolution Testing
Abstract
Herein, this work aimed to develop an ultraviolet spectrophotometric assay for metformin HCl in comparative dissolution testing along with the acid stage medium due to low molar absorptivity.
Metformin HCl was incorporated into the immediate tablet formulation to mimic the analytical matrix system. The dissolution validation procedure was carried out by linearity, accuracy, precision, the limit of quantification, filter compatibility, and aliquot stability that fulfil the USP method for validation of dissolution procedure, particularly assay of the analyte.
The results revealed that metformin HCl had difficulty quantifying in acid pH due to the absence UV-band peak. The addition of pH-shifting agents promoted better performance for metformin quantification. Therefore, the method was successfully developed along with R2, predicted R2, accuracy, and precision of 0.9999, 0,9998, 100.57%, and 1.27%, respectively. In addition, it had the minimum placebo interference (0.47%) and was stable for long-term storage under determined conditions.
Keywords:
Metformin HCl, Comparative dissolution testing, ultraviolet spectrophotometer, validation
References
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[2] Chen M-L, Blume H, Beuerle G, Mehta M, Potthast H, Brandt A, et al. Summary report of second EUFEPS/AAPS conference on global harmonization in bioequivalence. Eur J Pharm Sci 2019;127:24–8. https://doi.org/10.1016/j.ejps.2018.10.019.
[3] Mehta M, Blume H, Beuerle G, Tampal N, Schug B, Potthast H, et al. The global bioequivalence harmonisation initiative: Report of EUFEPS/AAPS third conference. Eur J Pharm Sci 2020;151:105383. https://doi.org/10.1016/j.ejps.2020.105383.
[4] Xie F, Ji S, Cheng Z. In vitro dissolution similarity factor (f2) and in vivo bioequivalence criteria, how and when do they match? Using a BCS class II drug as a simulation example. Eur J Pharm Sci 2015;66:163–72. https://doi.org/10.1016/j.ejps.2014.10.002.
[5] Poluyanov AM, Kochug A, Mitrofanova LS, Nikitin ID, Vergasov OYu, Shohin IE. Development, Validation and Approbation Analytical Method for the Quantitative Determination of Taurine by HPLC-UV Method in the Test of Comparative Dissolution Kinetics. Drug Dev Regist 2023;12:62–72. https://doi.org/10.33380/2305-2066-2023-12-2-62-72.
[6] Chapler MR, Ray SD. Biguanides. Ref. Module Biomed. Sci., Elsevier; 2023. https://doi.org/10.1016/B978-0-12-824315-2.00201-3.
[7] BPOM. Peraturan Badan Pengawas Obat dan Makanan Nomor 65 Tahun 2022 tentang Daftar Obat Generik Tertentu Wajib Uji Bioekuivalensi 2022.
[8] Alsulais HM, Alqaisum AK, Aldoulah AA, Mohsin AA, Ghonaim HM. Comparative Study of Brand and Generics Ciprofloxacin Tablets Available in the Saudi Market. Dissolution Technol 2023;30:GC12–8. https://doi.org/10.14227/DT300223PGC12.
[9] Renukuntla J, Palakurthi SS, Bolla PK, Clark BA, Boddu SHS, Manda P, et al. Advances in in-vitro bioequivalence testing methods for complex ophthalmic generic products. Int J Pharm 2022;627:122209. https://doi.org/10.1016/j.ijpharm.2022.122209.
[10] Matsui K, Nakamichi K, Nakatani M, Yoshida H, Yamashita S, Yokota S. Lowly-buffered biorelevant dissolution testing is not necessarily biopredictive of human bioequivalence study outcome: Relationship between dissolution and pharmacokinetics. Int J Pharm 2023;631:122531. https://doi.org/10.1016/j.ijpharm.2022.122531.
[11] Hernández B, Pflüger F, Kruglik SG, Cohen R, Ghomi M. Protonation–deprotonation and structural dynamics of antidiabetic drug metformin. J Pharm Biomed Anal 2015;114:42–8. https://doi.org/10.1016/j.jpba.2015.04.041.
[12] Sano AY, Lourenço FR. Measurement uncertainty arising from sampling and analytical steps of dissolution test of prednisone tablets. J Pharm Biomed Anal 2023;234:115501. https://doi.org/10.1016/j.jpba.2023.115501.
[13] Azis SBA, Syafika N, Qonita HA, Mahmud TRA, Abizart A, Permana AD. Application of validated spectrophotometric method to quantify metformin in the development of glucose-responsive microparticles loaded dissolving microneedles. Microchem J 2022;183:108051. https://doi.org/10.1016/j.microc.2022.108051.
[14] Kannaiah KP, Sugumaran A. Environmental benign AQbD based estimation of ketoconazole and beclomethasone by RP-HPLC and multi-analytical UV spectrophotometric method. Microchem J 2022;172:106968. https://doi.org/10.1016/j.microc.2021.106968.
[15] Kaur M, Mittal SK, Chawla R. Simultaneous estimation of tramadol and piroxicam by UV spectrophotometer and RP-HPLC. Mater Today Proc 2022;48:1735–9. https://doi.org/10.1016/j.matpr.2021.10.041.
[16] Mubeen G, Noor K. Spectrophotometric Method for Analysis of Metformin Hydrochloride. Indian J Pharm Sci 2009;71:100–2. https://doi.org/10.4103/0250-474X.51947.
[17] Choiri S, Ainurofiq A. Spectrophotometric analysis of desloratadine multicomponent crystal formulation: Comparison of conventional methods and chemometric analysis. Molekul 2020;15:1–8. https://doi.org/10.20884/1.jm.2020.15.1.560.
[18] USP. <1092>The dissolution procedure: Development and Validation. United Stated Pharmacopoeia 42-Natl. Formul. 37, Rockville, Maryland, USA: The United States Pharmacopeial Convention; 2019, p. 7178–97.
[19] Lawrence M, Paulraj EI, Rajesh P. Spectroscopic characterization, electronic transitions and pharmacodynamic analysis of 1-Phenyl-1,3-butanedione: An effective agent for antipsychotic activity. Chem Phys Impact 2023;6:100226. https://doi.org/10.1016/j.chphi.2023.100226.
[20] Sonntag E, Kolář J, Djukaj S, Lehocký R, Štěpánek F. Accelerated reactive dissolution model of drug release from long-acting injectable formulations. Eur J Pharm Biopharm 2023;189:122–32. https://doi.org/10.1016/j.ejpb.2023.06.003.
[21] Horkovics-Kovats S. Disintegration Rate and Properties of Active Pharmaceutical Ingredient Particles as Determined from the Dissolution Time Profile of a Pharmaceutical Formulation: An Inverse Problem. J Pharm Sci 2014;103:456–64. https://doi.org/10.1002/jps.23767.
[22] Uhrovčík J. Strategy for determination of LOD and LOQ values – Some basic aspects. Talanta 2014;119:178–80. https://doi.org/10.1016/j.talanta.2013.10.061.
[23] Hidayah SN, Hastuti AAMB. Comprehensive estimation of measurement uncertainty in determination of antioxidant activity in natural product by 2,2ʹ-diphenil-1-picrylhydrazyl (DPPH) radical scavenging assay. Chem Pap 2023;77:4579–87. https://doi.org/10.1007/s11696-023-02808-1.
