COMPARATIVE IN VITRO DISSOLUTION STUDY ON METFORMIN MARKET PRODUCTS USING DIFFERENT DISSOLUTION APPARATUSES

  • HANAN M. HASHEM Industrial Pharmacy Laboratory, Medical and Pharmaceutical Chemistry Department, Division of Pharmaceutical Industries, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt
  • AYA R. ABDOU Industrial Pharmacy Laboratory, Medical and Pharmaceutical Chemistry Department, Division of Pharmaceutical Industries, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt
  • NADIA M. MURSI Industrial Pharmacy Laboratory, Medical and Pharmaceutical Chemistry Department, Division of Pharmaceutical Industries, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt
  • LAILA H. EMARA Industrial Pharmacy Laboratory, Medical and Pharmaceutical Chemistry Department, Division of Pharmaceutical Industries, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt

Abstract

Objective: This study was proposed to evaluate and compare the in vitro dissolution profiles of six Metformin Hydrochloride (MH) market products.


Methods: Different dissolution apparatuses (USP apparatus II, IV and beaker method) were used to evaluate the dissolution profiles (in phosphate buffer, pH 6.8) of two immediate release (IR) generic products of Metformin Hydrochloride (MH): Cidophage® 1000 mg (G1, Egyptian market) and Metformin arrow® 1000 mg (G2, French market) with respect to the reference products named Glucophage® 850 mg (R1, Egyptian market and R2, French market). In addition to a generic controlled-release (CR) product; Cidophage Retard® 850 mg (G3) versus the reference product; Glucophage XR® 1000 mg (R3) (both from Egyptian market). Dissolution efficiency (D. E.) and the similarity factor (f2) were calculated. Weight uniformity, hardness, tablet dimensions and MH content were measured.


Results: Results of the three apparatuses showed that MH IR products studied (reference and generics) did not meet the 75% USP 30 specifications for MH dissolved at 30 min. For MH CR products, Glucophage XR® did not fulfill the USP release criteria, while Cidophage Retard® did. USP apparatus IV revealed the highest sensitivity and discriminative capability.


Conclusion: Generally, MH IR generics (G1 and G2) might be interchangeable with the innovator product (Glucophage®). However, Cidophage Retard® might not be interchangeable with Glucophage XR®.

Keywords: Metformin Hydrochloride, Flow-through cell, Immediate release, Controlled release

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References

1. Jantratid E, De Maio V, Ronda E, Mattavelli V, Vertzoni M, Dressman J. Application of bio-relevant 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.
2. Tsume Y, Igawa N, Drelich AJ, Ruan H, Amidon GE, Amidon GL. The in vivo predictive dissolution for immediate release dosage of donepezil and danazol, BCS class IIc drugs, with the GIS and the USP II with biphasic dissolution apparatus. J Drug Delivery Sci Technol 2019. https://doi.org/10.1016/j.jddst.2019.01.035
3. Emara LH, El-Ashmawy AA, Taha N. Stability and bioavailability of diltiazem/polyethylene oxide matrix tablets. Pharm Dev Technol 2018;23:1057-66.
4. Emara LH, Emam MF, Taha NF, Raslan HM, El-Ashmawy A. A simple and sensitive HPLC/UV method for determination of meloxicam in human plasma for bioavailability and bioequivalence studies. J Appl Pharm Sci 2016;6:012-9.
5. Emara LH, Emam MF, Taha NF, El-ashmawy AA, Mursi NM. In vitro dissolution study of meloxicam immediate-release products using flow-through cell (USP apparatus 4) under different operational conditions. Int J Pharm Pharm Sci 2014b;6:254-60.
6. Zaborenko N, Shi Z, Corredor CC, Smith Goettler BM, Zhang L, Hermans A, et al. First-principles and empirical approaches to predicting in vitro dissolution for pharmaceutical formulation and process development and for product release testing. AAPS J 2019;21:32.
7. Maggio RM, Castellano PM, Kaufman TS. A new principal component analysis-based approach for testing “similarity” of drug dissolution profiles. Eur J Pharm Sci 2008;34:66-77.
8. Wähling C, Schröter C, Hanefeld A. Flow-through cell method and IVIVR for poorly soluble drugs. Dissolution Technol 2011;18:15-25.
9. Emara L, El-Menshawi B, Estefan M. In vitro-in vivo correlation and comparative bioavailability of vincamine in prolonged-release preparations. Drug Dev Ind Pharm 2000;26:243-51.
10. Emara LH, Abdelfattah FM, Taha NF, El-Ashmawy AA, Mursi NM. In vitro evaluation of ibuprofen hot-melt extruded pellets employing different designs of the flow-through cell. Int J Pharm Pharm Sci 2014a;6:192-7.
11. Emara LH, Abdou AR, El-Ashmawy AA, Badr RM, Taha NF, Mursi NM. In vitro release evaluation of gastroretentive amoxicillin floating tablets employing a specific design of the flow-through cell. Dissolution Technol 2013;20:27-35.
12. Emara LH, Taha NF, Mursi NM. Investigation of the effect of different flow-through cell designs on the release of diclofenac sodium SR tablets. Dissolution Technol 2009;16:23-31.
13. Fotaki N, Reppas C. The flow-through cell methodology in the evaluation of intraluminal drug release characteristics. Dissolution Technol 2005;12:17-21.
14. Krämer J, Stippler E. Experiences with USP apparatus 4 calibration. Dissolution Technol 2005;12:33-9.
15. Beyssac E, Lavigne J. Dissolution study of active pharmaceutical ingredients using the flow-through apparatus USP 4. Dissolution Technol 2005;12:23-5.
16. Bhattachar SN, Wesley JA, Fioritto A, Martin PJ, Babu SR. Dissolution testing of a poorly soluble compound using the flow-through cell dissolution apparatus. Int J Pharm 2002;236:135-43.
17. Tang J, Srinivasan S, Yuan W, Ming R, Liu Y, Dai Z, et al. Development of a flow-through USP 4 apparatus drug release assay for the evaluation of amphotericin B liposome. Eur J Pharm Biopharm 2019;134:107-16.
18. Emara LH, Elsayed EW, El-Ashmawy AA, Abdou AR, Morsi NM. The flow-through cell as an in vitro dissolution discriminative tool for evaluation of gliclazide solid dispersions. J Appl Pharm Sci 2017;7:70-7.
19. de Carvalho Mendes T, Simon A, Menezes JCV, Pinto EC, Cabral LM, de Sousa VP. Development of USP apparatus 3 dissolution method with IVIVC for extended-release tablets of metformin hydrochloride and development of a generic formulation. Chem Pharm Bull 2019;16:23-31.
20. Adikwu MU, Yoshikawa Y, Takada K. Pharmacodynamic–pharmacokinetic profiles of metformin hydrochloride from a mucoadhesive formulation of a polysaccharide with antidiabetic property in streptozotocin-induced diabetic rat models. Biomaterials 2004;25:3041-8.
21. Hu LD, Liu Y, Tang X, Zhang Q. Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets. Eur J Pharm Biopharm 2006;64:185-92.
22. Stepensky D, Friedman M, Srour W, Raz I, Hoffman A. Preclinical evaluation of pharmacokinetic–pharmacodynamic rationale for oral CR metformin formulation. J Controlled Release 2001;71:107-15.
23. Frias JP. Fixed-dose combination of ertugliflozin and metformin hydrochloride for the treatment of type 2 diabetes. Expert Rev Endocrinol Metab 2019;14:75-83.
24. Adegbola AJ, Awobusuyi OJ, Adeagbo BA, Oladokun BS, Owolabi AR, Soyinka JO. Bioequivalence study of generic metformin hydrochloride in healthy nigerian volunteers. J Explor Res Pharmacol 2017;2:78-84.
25. Fujii A, Yasui Furukori N, Nakagami T, Niioka T, Saito M, Sato Y, et al. Comparative in vivo bioequivalence and in vitro dissolution of two valproic acid sustained-release formulations. Drug Des Dev Ther 2008;2:139-44.
26. 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.
27. Oner ZG, Polli JE. Authorized generic drugs: an overview. AAPS PharmSciTech 2018;19:2450-8.
28. 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.
29. 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. Dissolution Technol 2012;51-5.
30. Prithi IJ, Chowdhury SF, Tasneem S. Comparative in vitro dissolution test and other physicochemical parameters of some commercially available metformin HCl brands in Bangladesh. J Pharm Innov 2018;7:5-8.
31. Stuart AV, Clement Y, Sealy P, Lobenberg R, Montane Jaime L, Maharaj R, et al. Comparing the dissolution profiles of seven metformin formulations in simulated intestinal fluid. Dissolution Technol 2015;22:17-22.
32. Wong SS, Ngo S. Use of in vitro dissolution testing to assess multiple generic metformin tablets. Br J Pharm Res 2018;21:1-9.
33. Afifi SA, Ahmadeen S. A comparative study for evaluation of different brands of metformin hydrochloride 500 mg tablets marketed in Saudi Arabia. Life Sci J 2012;9:4260-6.
34. Sougi A, Ofori Kwakye K, Kuntworbe N, Kipo SL, El Boakye Gyasi M. Evaluation of the physicochemical and in vitro dissolution properties of metformin hydrochloride tablet brands marketed in five cities in ghana. Br J Pharm Res 2016;1:1-14.
35. Chandrasekaran AR, Jia CY, Theng CS, Muniandy T, Muralidharan S, Dhanaraj SA. In vitro studies and evaluation of metformin marketed tablets-Malaysia. J Appl Pharm Sci 2011;3:5-8.
36. United State Pharmacopeia and National Formulary USP 40; The United States Pharmacopeial Convention, Inc: Rockville MD; 2017.
37. United State Pharmacopeia and National Formulary USP 30-NF 25; The United States Pharmacopeial Convention, Inc: Rockville MD; 2007.
38. Moore J, Flanner H. Mathematical comparison of dissolution profiles. Pharmaceutical Technol 1996;20:64-74.
39. Food and Drug Administration. Guidance for Industry: Dissolution Testing of Immediate-Release Solid Oral Dosage Forms; 1997.
40. Khan K, Rhodes CT. Effect of compaction pressure on the dissolution efficiency of some direct compression systems. Pharm Acta Helv 1972;47:594-607.
41. Anderson N, Bauer M, Boussac 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.
42. Hamdan II, Jaber AKB. Pharmaceutical evaluation of metformin HCl products available in the Jordanian market. Jordan J Pharm Sci 2010;3:1-6.
43. Hurtado y de la Peña M, Alvarado YV, Miriam Domínguez Ramírez A, Rosa Cortes Arroyo A. Comparison of dissolution profiles for albendazole tablets using USP apparatus 2 and 4. Drug Dev Ind Pharm 2003;29:777-84.
44. Crison JR, Timmins P, Keung A, Upreti VV, Boulton DW, Scheer BJ. Biowaiver approach for biopharmaceutics classification system class 3 compound metformin hydrochloride using in silico modeling. J Pharm Sci 2012;101:1773-82.
45. Emara LH, Taha NF, El-Ashmawy AA, Raslan HM, Mursi NM. A rapid and sensitive bioanalytical HPLC method for determining diclofenac sodium in human plasma for bioequivalence studies. J Liq Chromatogr Relat Technol 2012;35:2203-16.
46. Medina JR, Salazar DK, Hurtado M, Cortes AR, Dominguez Ramirez, Miriam A. 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.
47. Medina JR, Aguilar E, Haurtado M. Dissolution behavior of carbamazepine suspensions using the usp dissolution apparatus 2 and the flow-through cell method with simulated GI fluids. Int J Pharm Pharm Sci 2017;9:111-6.
48. 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.
49. McCarthy LG, Kosiol C, Healy AM, Bradley G, Sexton JC, Corrigan OI. Simulating the hydrodynamic conditions in the United States Pharmacopeia paddle dissolution apparatus. AAPS PharmSciTech 2003;4:83-98.
50. Kukura J, Baxter J, Muzzio F. Shear distribution and variability in the USP apparatus 2 under turbulent conditions. Int J Pharm 2004;279:9-17.
51. Gite S, Chogale M, Patravale V. Development and validation of a discriminating dissolution method for atorvastatin delayed-release nanoparticles using a flow-through cell: a comparative study using USP apparatus 4 and 1. Dissolution Technol 2016;23:14-20.
52. Sheorey SD, Hinge MA, Sengupta R, Menon BV. Pharmaceutical equivalence between different brands of Metformin Hydrochloride tablets. J Pharm Res 2012;5:3456-9.
53. Block L, Schemling L, Couto A, Mourao S, Bresolin T. Pharmaceutical equivalence of metformin tablets with various binders. J Appl Pharm Sci 2008;29:29-35.
54. Berthelsen R, Holm R, Jacobsen J, Kristensen J, Abrahamsson B, Müllertz A. Dissolution model development: formulation effects and filter complications. Dissolution Technol 2016;23:6-12.
55. Shaw SJ, Krauss GL. Generic antiepileptic drugs. Curr Treat Options Neurol 2008;10:260-8.
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HASHEM, H. M., A. R. ABDOU, N. M. MURSI, and L. H. EMARA. “COMPARATIVE IN VITRO DISSOLUTION STUDY ON METFORMIN MARKET PRODUCTS USING DIFFERENT DISSOLUTION APPARATUSES”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 11, no. 9, Aug. 2019, pp. 65-72, doi:10.22159/ijpps.2019v11i9.34711.
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