In silico and in vitro methods to optimize the performance of experimental gastroretentive floating mini-tablets

Abstract

Context: Development of floating drug delivery systems (FDDS) is challenging. To facilitate this task, an evaluation method was proposed, which allows for a combined investigation of drug release and flotation.

Objective: It was the aim of the study to use functionalized calcium carbonate (FCC)-based lipophilic mini-tablet formulations as a model system to design FDDS with a floating behavior characterized by no floating lag time, prolonged flotation and loss of floating capability after complete drug release.

Materials and methods: Release of the model drug caffeine from the mini-tablets was assessed in vitro by a custom-built stomach model. A cellular automata-based model was used to simulate tablet dissolution. Based on the in silico data, floating forces were calculated and analyzed as a function of caffeine release.

Results and discussion: Two floating behaviors were identified for mini-tablets: linear decrease of the floating force and maintaining of the floating capability until complete caffeine release. An optimal mini-tablet formulation with desired drug release time and floating behavior was developed and tested.

Conclusion: A classification system for a range of varied floating behavior of FDDS was proposed. The FCC-based mini-tablets had an ideal floating behavior: duration of flotation is defined and floating capability decreases after completion of drug release.

• Drug release
• floating force
• flotation
• functionalized calcium carbonate
• mini-tablet formulations

Acknowledgements

Dr Maxim Puchkov and Prof. Dr Jörg Huwyler have contributed equally to the present work. The author thank Dr Daniel E. Gerard (Omya International AG) for preparing FCC samples and to Rainer Alles for technical assistance.

Declaration of interest

Financial support for the PhD thesis of Veronika Eberle was kindly provided by Omya International AG (Oftringen, Switzerland).