Pharmacokinetic study of mucoadhesive metformin pellets in rats

초록

Previously, we have reported the preparation and characterization of mucoadhesive pellets of metformin hydrochloride using four high-viscosity polymers including hydroxymethylcellulose (HPMC), HPMC/carbopol, sodium carboxylmethylcellulose (Na-CMC) and sodium alginate (Na-Alg) (Piao et al., Arch Pharm Res 32:391-397, 2009). Here, pharmacokinetic and pharmacodynamic evaluation of these metformin pellets was performed. Metformin pellets were administered orally to normal and streptozotocin-induced diabetic rats at 100 mg/kg dose and the blood concentration of metformin and blood glucose levels were determined. The area under the plasma concentration versus time curve from the Na-Alg-coated metformin pellets in normal rats was 69.93 ± 39.63 μg h/mL and it was the highest among tested, followed by Na-CMC-coated pellets (58.38 ± 5.19), HPMC/carbopol-coated pellets (52. 24 ± 5. 29), HPMC-coated pellets (42. 70 ± 14. 29) and metformin aqueous solution (33. 49 ± 2. 04). The Cmax from the Na-Alg-coated metformin pellets in normal rats was 29. 47 ± 10.74 μg/mL and it was the highest among tested, followed by Na-CMC-coated pellets (15. 10 ± 2. 73), HPMC/carbopol-coated pellets (11. 38 ± 3. 04), HPMC-coated pellets (11. 29 ± 3. 85) and metformin aqueous solution (6. 92 ± 0. 83). The area under the effect versus time curve of the Na-Alg-coated pellets in diabetic rats was the highest as 670. 01 ± 211. 20 μg h/mL, followed by CMC-coated pellets (542. 42 ± 116. 93), HPMC-coated pellets (539. 46 ± 189. 91), HPMC/carbopol-coated pellets (444. 03 ± 90. 30), and metformin aqueous solution (199. 28 ± 31. 07). These data show that the Na-Alg-coated pellets were found to be the best among tested as a new mucoadhesive formulation for metformin hydrochloride prepared by the powder layering technique with a centrifugal fluidizing-granulator. © 2012 The Korean Society of Pharmaceutical Sciences and Technology.

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