Biopredictive conditions

Asma Radwan's picture

Bio-Predictive Tablet Disintegration: Effect of Water Diffusivity, Fluid Flow, Food Composition and Test Conditions

Journal Title, Volume, Page: 
European Journal of Pharmaceutical Sciences Volume 57, 16 June 2014, Pages 273–279
Year of Publication: 
Asma Radwan
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Manfred Wagner
Max Planck Institute for Polymer Research, Mainz, Germany
Gordon L. Amidon
College of Pharmacy, The University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USA
Peter Langguth
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
Preferred Abstract (Original): 

Food intake may delay tablet disintegration. Current in vitro methods have little predictive potential to account for such effects. The effect of a variety of factors on the disintegration of immediate release tablets in the gastrointestinal tract has been identified. They include viscosity of the media, precipitation of food constituents on the surface of the tablet and reduction of water diffusivity in the media as well as changes in the hydrodynamics in the surrounding media of the solid dosage form. In order to improve the predictability of food affecting the disintegration of a dosage form, tablet disintegration in various types of a liquefied meal has been studied under static vs. dynamic (agitative) conditions. Viscosity, water diffusivity, osmolality and Reynolds numbers for the different media were characterized. A quantitative model is introduced which predicts the influence of the Reynolds number in the tablet disintegration apparatus on the disintegration time. Viscosity, water diffusivity and media flow velocity are shown to be important factors affecting dosage form disintegration. The results suggest the necessity of considering these parameters when designing a predictive model for simulating the in vivo conditions. Based on these experiments and knowledge on in vivo hydrodynamics in the GI tract, it is concluded that the disintegration tester under current pharmacopoeial conditions is operated in an unphysiological mode and no bioprediction may be derived. Recommendations regarding alternative mode of operation are made.

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