Physicochemical stability of three generic brands of metformin in solution
Resumen
Pharmacological management of insulin resistance and dyslipidemias in children and adolescents is mandatory to prevent metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM).
Material and method: extemporaneous formulations were developed from 500 mg tablets of three brands of generic metformin: Medimart®, Farmacias del Ahorro®, and Primer Nivel®, with agreeable flavor, color, and consistency and dose adjusted for ease of administration. Their physicochemical integrity was determined under different storage conditions: 25oC with light, 25oC in darkness, at 4oC and 40oC. The stability of the drug was determined by ultra performance liquid chromatography
with ultraviolet detection (UPLC-UV) and by measuring the pH of the stored solution; the mobile phase was phosphate buffer (KH2PO4) 0.1 M, pH = 6.5, sodium dodecyl sulfate (SDS) 4.6 mM and acetonitrile (63:7:30) at 0.8 mL/min, VARIAN Pursuit C8 150 × 3.9 mm column tempered at 40oC, with detection at 236 nm.
Results: All the commercial brands of metformin were stable under all storage conditions for up to 30 days. They retained more than 90% of the initial quantity of the active drug, with pH of 7.4 ± 0.3.
Conclusion: extemporaneous formulations of metformin can be made with both the innovative drug and with generics; money can be saved, with the certainty that they will retain their physicochemical properties.
Citas
Garnett SP, Baur LA, Noakes M, Steinbeck K, Woodhead HJ, Burrell S, Chisholm K, Broderick CR, Parker R, De S, Shrinivasan S, Hopley L, Hendrie G, Ambler GR, Kohn MR, Cowell CT. Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers - RESIST. A randomised control trial investigating the effects of two different diets on insulin sensitivity in young people with insulin resistance and/or pre-diabetes. BMC Public Health. 2010;10:575. doi: 10.1186/1471-2458-10-575
Ventura EE, Davis JN, Alexander KE, Shaibi GQ, Lee W, Byrd-Williams CE, Toledo-Corral CM, Lane CJ, Kelly LA, Weigensberg MJ, Goran MI. Dietary intake and the metabolic syndrome in overweight Latino children. J Am Diet Assoc 2008;108:1355-9. doi: 10.1016/j.jada.2008.05.006
Kanekara A, Sharma M. Pharmacological Approaches for Management of Child and Adolescent Obesity. J Clin Med Res 2010;2:105-11. doi: 10.4021/jocmr2010.05.288w
Lalau JD, Lacroix C, Compagnon P. Role of metformin accumulation in metformin-associated lactic acidosis. Diabetes Care 1995;18:779-84.
Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334:574-9.
Hermann LS, Scherstein B, Bitzen PO. Therapeutic comparison of metformin and sulfonylurea, alone, and in various combinations. A double-blind controlled study. Diabetes Care 1994;17:1100-9.
Fulgencio JP, Kohl C, Girard J, Pegorier JP. Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and on specific gene expression in cultured hepatocytes. Biochem Pharmacol 2001;62:439-46.
Alemon-Medina R, Coria-Jimenez R, Ramirez-Mendiola B, Rivera-Espinosa L, Garcia-Alvarez R, Juárez-Olguin H, Chavez-Pacheco JL. Physicochemical and microbiological stabilities of a sweetened and calorie-free metformin extemporaneous formulation for pediatrics. Lat Am J Pharm
;31:1253-60.
PROYECTO-NOM-177-SSA1-2013. Draft Official Mexican Standard-177-SSA1-2013. Official Gazette of the Federation. 2013.
Kendall DL, Amin R, Clayton PR. Metformin in the treatment of obese children and adolescents at risk of type 2 diabetes. Pediatr Drugs 2014;16:13-20.
Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int J Obes 2011;35:891-8.
Glueck CJ, Fontaine RN, Wang P, et al. Metformin reduces weight, centripetal obesity, insulin, leptin and low density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with BMI>30. Metabolism 2011;50:856–61.
Diaz de Leon-Castañeda C, Altagracia-Martinez M, Kravzov- Jinich J, Cardenas-Elizalde MR, Moreno-Bonett C, Martinez- Nunez JM. Cost-effectiveness study of oral hypoglycemic agents in the treatment of outpatients with type 2 diabetes attending a public primary care clinic in Mexico City. Clinicoecon Outcomes Res 2012;4:57–65. doi: 10.2147/CEOR. S27826
Juarez-Olguin H. Uso de fórmulas magistrales en pediatría. Acta Pediatrica de Mexico. 2011;32:175-176.
Chavez-Pacheco JL, Rivera-Espinosa L, Alemon-Medina R, Gonzalez-Zamora JF, Ramirez-Mendiola B, Flores-Perez J, Juarez-Olguin H, Flores-Perez C. Development and sedative
effect of a new formulation of midazolam in chocolate bars. Lat Am J Pharm 2011;30:1977-84.
Nunn AJ. 2003. Making medicines that children can take. Arch Dis Child 2003;88:369-71.
Schirm E, Tobi H, De Jong-van den Berg LTW. Risk factors for unlicensed and off-label drug use in children outside the hospital. Pediatrics 2003;111:291-5.
Strickley RG, Iwata Q, Wu S, Dahl TC. Pediatric Drugs -A Review of Commercially Available. Journal of Pharmaceutical Sciences 2008;97:1731- 1774.
Young DA, Bowen WH. 1990. The influence of sucralose on bacterial metabolism. J Dent Res 1990;69:1480-4.
Derechos de autor 2015 Acta Pediátrica de México
Esta obra está bajo licencia internacional Creative Commons Reconocimiento 4.0.
