Mechanistic Understanding of Food Effects: Water Diffusivity in Gastrointestinal Tract Is an Important Parameter for the Prediction of Disintegration of Solid Oral Dosage Forms

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RESEARCH PRODUCT

Mechanistic Understanding of Food Effects: Water Diffusivity in Gastrointestinal Tract Is an Important Parameter for the Prediction of Disintegration of Solid Oral Dosage Forms

Gordon L. Amidon Asma Radwan Sandro Ebert Manfred Wagner Andrea Mariela Amar Kerstin Münnemann Peter Langguth

subject

Sucrose Magnetic Resonance Spectroscopy Sodium Pharmaceutical Science chemistry.chemical_element TABLETS Methylcellulose Sodium Chloride Thermal diffusivity BIOPREDICTIVE MEDIA Dosage form Ciencias Biológicas Viscosity Hypromellose Derivatives Osmotic Pressure DISSOLUTION Drug Discovery Osmotic pressure Dissolution Aqueous solution Chromatography Viscosity Otras Ciencias Químicas Ciencias Químicas Bioquímica y Biología Molecular DIFFUSION COEFFICIENT Hypromellose Derivatives BIOPHARMACEUTIC PREDICTION chemistry Chemical engineering Molecular Medicine CIENCIAS NATURALES Y EXACTAS

description

Much interest has been expressed in this work on the role of water diffusivity in the release media as a new parameter for predicting drug release. NMR was used to measure water diffusivity in different media varying in their osmolality and viscosity. Water self-diffusion coefficients in sucrose, sodium chloride, and polymeric hydroxypropyl methylcellulose (HPMC) solutions were correlated with water uptake, disintegration, and drug release rates from trospium chloride immediate release tablets. The water diffusivity in sucrose solutions was significantly reduced compared to polymeric HPMC and molecular sodium chloride solutions. Water diffusivity was found to be a function of sucrose concentration in the media. Dosage form disintegration and drug release was to be affected by water diffusivity in these systems. This observation can be explained by hydrogen bonding formation between sugar molecules, an effect which was not expressed in sodium chloride solutions of equal osmolality. Water diffusivity and not media osmolality in general need to be considered to predict the effect of disintegration and dissolution media on drug release. Understanding the relevance of water diffusivity for disintegration and dissolution will lead to better parametrization of dosage form behavior in gastrointestinal (GI) aqueous and semisolid media. Fil: Radwan, Asma. University Mainz. Institute of Inorganic and Analytical Chemistry, Johannes Gutenberg; Alemania Fil: Ebert, Sandro. Max Planck Institute for Polymer Research; Alemania Fil: Amar, Andrea Mariela. Max Planck Institute for Polymer Research; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Münnemann, Kerstin. Max Planck Institute for Polymer Research; Alemania Fil: Wagner, Manfred. Max Planck Institute for Polymer Research; Alemania Fil: Amidon, Gordon L.. University of Michigan; Estados Unidos Fil: Langguth, Peter. University Mainz. Institute of Inorganic and Analytical Chemistry, Johannes Gutenberg; Alemania

year	journal	country	edition	language
2013-04-01	Molecular Pharmaceutics

https://doi.org/10.1021/mp3006209