IN VITRO RELEASE PERFORMANCE OF METFORMIN HYDROCHLORIDE FORMULATIONS USING THE FLOW-THROUGH CELL METHOD

Authors

  • JOSE RAUL MEDINA-LÓPEZ Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
  • FRIDA IRIANA MEDINA-MORALES Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
  • RAFAEL ALONSO GALVEZ LOMELIN Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
  • JUAN CARLOS RUIZ SEGURA Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
  • MARCELA HURTADO Departamento Sistemas Biologicos, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico

DOI:

https://doi.org/10.22159/ijap.2020v12i6.39230

Keywords:

Diabetes type 2, Flow-through cell method, Generic drug products, Metformin hydrochloride

Abstract

Objective: The objective of this work was to evaluate the in vitro release performance of metformin hydrochloride formulations (500-mg tablets) using the hydrodynamic environment of the flow-through cell method. Results were compared with those generated by the official dissolution test (USP basket apparatus).

Methods: The reference drug product and three generic formulations were tested with phosphate buffer pH 6.8 as dissolution medium. Dissolution profiles were carried out with an automated flow-through cell apparatus using laminar flow at 16 ml/min. Drug was quantified at 233 nm during 45 min. Dissolution profiles were compared with the calculation of f2 similarity factor, mean dissolution time, dissolution efficiency, t50% and t63.2%. Dissolution data were adjusted to several mathematical models such as Makoid-Banakar, Peppas-Sahlin, Weibull and Logistic.

Results: With the flow-through cell method and at 45 min less than 60% of metformin hydrochloride dissolved was found, while with the USP basket apparatus, less than 75% of the drug was found. Some generic formulations showed f2>50 with both USP apparatuses, but statistical comparisons of parameters indicated significant differences between their dissolution profiles and reference. Due to variability obtained no dissolution profiles were compared by model-dependent approach.

Conclusion: To demonstrate safe interchangeability between metformin hydrochloride generic formulations and reference bioequivalence studies should be performed. It is important post-marketing monitoring of the commercial formulations because health regulatory agencies of each country must ensure drug products with quality, safety, and efficacy at the lowest possible cost.

Downloads

Download data is not yet available.

References

Ruiz ME, Gregorini A, Talevi A, Volonte MG. Dissolution studies of generic medications: new evidence of deviations from the transitive principle. Dissolut Technol 2012;19:13‒24.

Sonal Sekhar M, Thunga G, Suhaj A. The story of metformin continues. J Pharm Pract Res 2014;44:289‒90.

Song R. Mechanism of metformin: a tale of two sites. Diabetes Care 2016;39:187‒9.

Hundal RS, Krssak M, Dufour S, Laurent D, Lebon V, Chandramouli V, et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000;49:2063‒9.

Lindenberg M, Kopp S, Dressman JB. Classification of orally administered drugs on the word health organization model list of essential medicines according to the biopharmaceutic classification system. Eur J Pharm Biopharm 2004;58:265‒78.

Food and Drug Administration. Guidance for Industry: Waiver on in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system; 2017. Available from: https://www.fda.gov/media/70963/download. [Last accessed on 10 Jun 2020].

United States Pharmacopeia and National Formulary USP 43-NF38; The United States Pharmacopeial Convention, Inc: Rockville MD; 2020.

Adegbola AJ, Awobusuyi OJ, Adeagbo BA, Oladokun BS, Owolabi AR, Soyinka JO. Bioequivalence study of generic metformin hydrochloride in healthy Nigerian volunteers. J Exp Res Pharmacol 2017;2:75‒81.

Olusola AM, Adekoya AI, Olanrewaju OJ. Comparative evaluation of physicochemical properties of some commercially available brands of metformin HCl tablets in lagos, Nigeria. J Appl Pharm Sci 2012;2:41‒4.

Villarroel Stuart A, Clement Y, Sealy P, Lobenberg R, Montane Jaime L, Maharaj RG, Maxwell A. Comparing the dissolution profiles of seven metformin formulations in simulated intestinal fluid. Dissolut Technol 2015;22:17‒21.

Oyetunde OO, Tayo F, Akinleye MO, Aina BA. In vitro equivalence studies of generic metformin hydrochloride tablets and propranolol hydrochloride tablets under biowaiver conditions in Lagos State, Nigeria. Dissolut Technol 2012;19:51‒5.

Akdag Y, Gulsun T, Izat N, Oner L, Sahin S. Comparison of dissolution profiles and apparent permeabilities of commercially available metformin hydrochloride tablets in Turkey. Dissolut Technol 2020;27:22‒9.

Hashem HM, Abdou AR, Mursi MN, Emara LH. Comparative in vitro dissolution study on metformin market products using different dissolution apparatuses. Int J Pharm Pharm Sci 2019;11:65‒72.

Kassahun H, Asres K, Ashenef A. In vitro quality evaluation of metformin hydrochloride tablets marketed in Addis Ababa. Bangl J Sci Ind Res 2019;54:169‒76.

Prithi IJ, Chowdhury SF, Chowdhury ST. Comparative in vitro dissolution test and other physicochemical parameters of some commercially available metformin HCl brands in Bangladesh. Pharma Innov J 2018;7:5‒8.

Zakeri Milani P, Nayyeri Maleki P, Ghanbarzadeh S, Nemati M, Valizadeh H. In vitro bioequivalence study of 8 brands of metformin tablets in Iran market. J Appl Pharm Sci 2012;2:194‒7.

Jantratid E, De Maio V, Ronda E, Mattavelli V, Vertzoni M, Dressman JB. Application of biorelevant dissolution tests to the prediction of in vivo performance of diclofenac sodium from an oral modified-release pellet dosage form. Eur J Pharm Sci 2009;37:434‒41.

Jinno J, Kamada N, Miyake M, Yamada K, Mukai T, Odomi M, et al. In vitro-in vivo correlation for wet-milled tablet of poorly water-soluble cilostazol. J Controlled Release 2008;130:29‒37.

COFEPRIS. Listado Actualizado de Medicamentos de Referencia 2020/01, Mexico. Available from: https://www.gob.mx/ cms/uploads/attachment/file/534996/listado_de_medicamentos_de_Referencia_.pdf. [Last accessed on 10 Jun 2020].

ICH. Harmonized Tripartite Guideline. Q2B Validation of Analytical Procedures: Methodology. International Conference on Harmonization; 1996. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q2b-validation-analytical-procedures-methodology. [Last accessed on 10 Jun 2020]

Yuksel N, Kanik AE, Baykara T. Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and independent-methods. Int J Pharm 2000;209:57‒67.

Collier PS. The interpretation of in vivo means dissolution time data. In: Benet L, Z, Levy G, Ferraiolo BL. eds. Pharmacokinetics. Springer-Verlang. Boston, USA; 1984.

Tanigawara Y, Yamaoka K, Nakagawa T, Unzo T. New method for the evaluation of in vitro dissolution time and disintegration time. Chem Pharm Bull 1982;30:1088‒90.

Podczeck F. Comparison of in vitro dissolution profiles by calculating mean dissolution time (MDT) or mean residence time (MRT). Int J Pharm 1993;97:93‒100.

Anderson NH, Bauer M, Bousaac N, Khan Malek R, Munden P, Sardaro M. An evaluation of fit factors and dissolution efficiency for the comparison of in vitro dissolution profiles. J Pharm Biomed Anal 1998;17:811‒22.

Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DD Solver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J 2010;12:263‒71.

Medina JR, Ortiz HD, Hurtado M, Dominguez Ramirez AM. Influence of dose and the USP basket and flow-through cell dissolution apparatuses in the release kinetics of metronidazole immediate-release products. Int J Res Pharm Sci 2014;5:137‒46.

Medina JR, Salazar DK, Hurtado M, Cortes AR, Dominguez Ramirez AM. Comparative in vitro dissolution study of carbamazepine immediate-release products using the USP paddles method and the flow-through cell system. Saudi Pharm J 2014;22:141‒7.

Langenbucher F, Benz D, Kurth W, Moller H, Otz M. Standardized flow-cell method as an alternative to existing pharmacopoeial dissolution testing. Pharm Ind 1989;51:1276‒81.

Moore JW, Flanner HH. Mathematical comparison of dissolution profiles. Pharm Technol 1996;20:64‒74.

WHO. Technical Report Series, no. 937, Annex 7. Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability; 2006. Available from: https://www.who.int/medicines/areas/quality_safety/ quality_assurance/MultisourcePharmaProductsGuidelinesRegistrationRequirementsInterchangeabilityTRS937Annex7.pdf. [Last accessed on 10 Jun 2020]

Hurtado M, Vargas Y, Dominguez Ramirez AM, Cortes AR. Comparison of dissolution profiles for albendazole tablets using USP apparatus 2 and 4. Drug Dev Ind Pharm 2003;29:777‒84.

Block LC, Schemling LO, Cuoto AG, Mourao SC, Bresolin TMB. Pharmaceutical equivalence of metformin tablets with various binders. Rev Cienc Farm Basica Appl 2008;29:29‒35.

Published

07-11-2020

How to Cite

MEDINA-LÓPEZ, J. R., MEDINA-MORALES, F. I., GALVEZ LOMELIN, R. A., RUIZ SEGURA, J. C., & HURTADO, M. (2020). IN VITRO RELEASE PERFORMANCE OF METFORMIN HYDROCHLORIDE FORMULATIONS USING THE FLOW-THROUGH CELL METHOD. International Journal of Applied Pharmaceutics, 12(6), 76–82. https://doi.org/10.22159/ijap.2020v12i6.39230

Issue

Section

Original Article(s)

Most read articles by the same author(s)

<< < 1 2