L Rivera-Espinosa, G Pérez-Guillé, JL Chávez-Pacheco, LM Torres-Espíndola, H Juárez-Olguín, R Alemón-Medina
BACKGROUND: Homemade fractions of metformin tablets to adjust paediatric doses are difficult to administer, unstable and yields variable doses. In this work, a liquid extemporaneous formulation of metformin, sweetened with 1% sucralose, is proposed.
PURPOSE: To determine the pharmacokinetics of the new formulation compared to the fractionated tablet in healthy adult volunteers and to demonstrate that it remains unaltered.
METHODS: Randomised, crossed and longitudinal clinical trial, in 12 healthy adult volunteers, 7 males and 5 females (n=12), 24.3 ± 1.8 years, with BMI = 24.9 ± 2.5. Eight blood samples were obtained in Whatman 903® cards at 0, 0.25, 0.5, 1, 2, 4, 8 and 12 hours after administration of 250 mg metformin. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol. Detection was carried out by UPLC and tandem mass spectrometry. Mobile phase: 5 mM ammonium acetate and ACN (80:20; v/v), 0.25 mL/min, isocratically. Pharmacokinetics was determined using WinNonlin Pro 3.1 software and analysed by one-way ANOVA (p ≤ 0.05).
RESULTS: The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r=0.9982). Samples were stable at 4°C for 17 hours and for 2 months at -80°C. The metformin formulation had a Cmax of 652 ng/mL and 550 ng/mL in the tablet. Tmax and ke were lower with the formulation (1.6 h vs. 1.8 h and 0.32 h-1 vs. 0.29 h-1). The AUC0-12 was virtually the same in both forms (F%=1.01).
CONCLUSIONS: The liquid formulation of metformin showed similar pharmacokinetics to the split tablet, but it additionally allows a more precise dose adjustment, ease of administration and uniformity of content.
KEYWORDS: metformin; pharmacokinetics; drug formulations