Category: Formulation and Quality
Purpose: Anti-diabetes bilayer tablets were designed with:
An extended release layer of Metformin HCl 500 mg in a Carbopol® polymer - based hydrophilic matrix
An immediate release layer of Glimepiride 2 mg.
The objective of the present work was to formulate the Glimepiride immediate release layer (2 mg) to be used in the design of anti-diabetes bilayer tablets having Metformin HCl 500 mg as the extended release layer.
Methods: A constrained mixture design was used to formulate the immediate release Glimepiride layer with disintegrant level (sodium starch glycolate) and binder type/amount (pregelatinized starch and polyvinylpyrrolidone (PVP) K-30) – as independent variables – Table 1. Lactose monohydrate was varied to achieve 100% w/w of the formulation. Output variables were the % drug release at 15 and 30 minutes, and assay; the target ranges were not less than 70% drug release in 30 minutes and assay of 90% to 110% of the label claim.
The design was suitable to estimate the linear effects of the three variables and curvature effects of sodium starch glycolate and PVP K-30 on drug release. In addition, interaction effects between sodium starch glycolate and the binders were used to explore how disintegrant and binder work together to influence drug release.
Eleven different Glimepiride (2 mg) layer formulations in the above range were manufactured. Glimepiride granules were prepared by high shear aqueous granulation, blended with microcrystalline cellulose, lubricated, and compressed into tablets using 14.0 x 9.0 mm capsule shaped punches to achieve bilayer tablets of total target tablet weight 815 mg (Metformin HCl extended release layer weight 650 mg and Glimepiride immediate release layer weight 165 mg) and hardness 20 kP.
Glimepiride dissolution studies were conducted for all formulations: USP apparatus 2 (Paddle), 75 RPM, 900 mL pH 7.8 phosphate buffer.
Results: The physical properties of the bilayer tablets were satisfactory. The assay and 30-minute dissolution of all batches were within limits – Table 2. As the polymers from the extended layer may interfere with the release of Glimepiride during stability, formulations with >95% drug dissolved were selected for further studies. A broader dissolution range was observed at 15 min compared to 30 min. Interactions between disintegrant and binder influenced the behavior of the drug release of the immediate release layer of the tablets.
Gaurang Parekh– Mumbai, Maharashtra, India
Vikrant Chadawar– Mumbai, Maharashtra, India
Kedar Chikhalikar– Mumbai, Maharashtra, India
Prachi More– Mumbai, Maharashtra, India
Ann Giovannitti-Jensen– Cleveland, Ohio
Elena Draganoiu– Lubrizol LifeSciences, Vaughan, Ontario, Canada
Elena Draganoiu– Lubrizol, Cleveland, OH