Category: Formulation and Quality
Purpose: The purpose of the study was to evaluate Carbopol® polymers in combination with microenvironmental pH modulators (buffering agents) to achieve improved stability and high drug loading for Metformin HCl extended release tablets.
Methods: Extended release Metformin HCl tablets were prepared by high shear aqueous granulation using Carbopol polymers in combination with other controlled release agents (hypromellose or sodium-CMC). Microenvironmental pH modulators (magnesium carbonate, magnesium oxide, magnesium hydroxide, sodium bicarbonate, sodium acetate, sodium hydrogen phosphate, trisodium phosphate, calcium carbonate, and potassium carbonate) were included to improve stability at high drug loading (62 – 80%).
The tablets were evaluated for chemical stability by HPLC after exposure in open Petri dishes to forced degradation conditions (80°C and 75 % RH for 5 days).
Based on the outcome of the forced degradation, formulations of Metformin HCl 500 mg extended release tablets were further developed to meet USP dissolution requirements and tested for stability under ICH accelerated conditions (40±2°C/75±5%RH).
Results: The formulations containing combinations of Carbopol polymers and magnesium-based buffering agents (magnesium hydroxide and magnesium oxide) showed improved stability at high drug loading - Table 1.
Among the buffering agents studied, magnesium hydroxide and magnesium oxide led to the lowest impurity levels and physically stable formulations. Inclusion of bicarbonates or carbonates was not recommended due to carbon dioxide generated during stability testing.
Metformin HCl 500 mg extended release tablets were developed based on the forced degradation results, using magnesium hydroxide as a buffering agent. The tablets (Lot 1) met the USP Test 4 dissolution requirements and were stable for 6 months under ICH accelerated stability conditions – Fig. 1.
Conclusion: Combinations of Carbopol® polymers and magnesium containing microenvironmental pH modulators (magnesium hydroxide and magnesium oxide) provided improved stability and high drug loading for Metformin HCl tablets. Metformin HCl 500 mg extended release tablets were successfully formulated to meet USP dissolution requirements and achieve stability under ICH accelerated conditions.
Carbopol is a registered trademark of The Lubrizol Corporation USA
Kedar Chikhalikar– Mumbai, Maharashtra, India
Vikrant Chadawar– Mumbai, Maharashtra, India
Liliana Miinea– Cleveland, Ohio
Elena Draganoiu– Lubrizol LifeSciences, Vaughan, Ontario, Canada
Elena Draganoiu– Lubrizol, Cleveland, OH