Physiological relevant in vitro evaluation of polymer coats for gastroretentive floating tablets

Abstract

Gastroretentive drug delivery systems are retained in the stomach for a sufficient time interval, releasing the drug in a controlled manner. According to literature, the floating principle is the most frequently used formulation approach for gastric retention. However, many publications lack information of the floating forces, the impact of different pH-values and almost no information exist concerning the resistance of the floating performance against physiological relevant stress. Therefore, we evaluated the performance of CO2-generating floating bilayer (drug and floating layer) tablets with respect to robustness, drug release profile, pH dependence and floating behaviour. Bilayer tablets were coated with a flexible and water permeable, but CO2-retaining polymer film of either polyvinyl acetate or ammonio-methacrylate copolymer type A. Metformin-HCl was used as a relevant model drug due to its dose-dependent and saturable absorption from the proximal part of the small intestine. To mimic physiological relevant mechanical stress conditions, recently developed dissolution stress tests with pulsed pressures were applied in addition to release studies according to the pharmacopeia. Bilayer tablets coated with polyvinyl acetate showed short floating lag times, reasonable floating strength values, floating durations of more than 24h in simulated gastric fluid and a robust and pH independent release of Metformin-HCl. Tablets coated with ammonio-methacrylate copolymer type A showed a higher permeability for the active ingredient combined with a decreased robustness of the inflated tablets. Both polymers can be used for balloon-like floating devices. The appropriate polymer has to be chosen dependent from the properties of the active ingredient and requested application of the delivery device. Furthermore, the dissolution stress test analysis is able to indicate possible safety issues of gastroretentive formulations as well as to characterise the robustness of formulation principles towards mechanical stresses of bio-relevant intensity.

Keywords: Bilayer tablets; Eudragit® RL 30D; Floating; Gastroretentive drug delivery systems; Kollicoat® SR 30D; Metformin-HCl; Stress test; Texture analyser.