Abstract
PurposeTo develop a model linking in vitro and in vivo erosion of extended release tablets under fasting and postprandial status.MethodsA nonlinear mixed-effects model was developed from the in vitro erosion profiles of four hydroxypropyl methylcellulose (HPMC) matrix tablets studied under a range of experimental conditions. The model was used to predict in vivo erosion of the HPMC matrix tablets in different locations of the gastrointestinal tract, determined by magnetic marker monitoring. In each gastrointestinal segment the pH was set to physiological values and mechanical stress was estimated in USP2 apparatus rotation speed equivalent.ResultsErosion was best described by a Michaelis–Menten type model. The maximal HPMC release rate (VMAX) was affected by pH, mechanical stress, HPMC and calcium hydrogen phosphate content. The amount of HPMC left at which the release rate is half of VMAX depended on pH and calcium hydrogen phosphate. Mechanical stress was estimated for stomach (39.5 rpm), proximal (93.3 rpm) and distal (31.1 rpm) small intestine and colon (9.99 rpm).ConclusionsThe in silico model accurately predicted the erosion profiles of HPMC matrix tablets under fasting and postprandial status and can be used to facilitate future development of extended release tablets.
Highlights
Extended release (ER) dosage forms are widely used to optimize drug concentration in plasma and improve patient compliance
Hydrophilic active pharmaceutical ingredient (API) are released by diffusion into the dissolution media, while less soluble API as well as the hydroxypropyl methylcellulose (HPMC) polymer itself are being released by progressive erosion of the gel layer [1,2,3,4]
The between tablet variability (BTV) was estimated to a coefficient of variation (CV) of 5.96% for VMAX, but was no longer supported on KM
Summary
Extended release (ER) dosage forms are widely used to optimize drug concentration in plasma and improve patient compliance. Their main application lies in the reduction of the dosing frequency for drugs with short elimination half-life and in the reduction of side effects occurring for drugs exhibiting highly variable plasma concentrations. Upon ingestion of an ER tablet, water will diffuse into its core, causing the HPMC matrix to swell and form a rubbery gel. Hydrophilic API are released by diffusion into the dissolution media, while less soluble API as well as the HPMC polymer itself are being released by progressive erosion of the gel layer [1,2,3,4]. The molecular weight and proportion of HPMC within an ER tablet can be modified to optimize the release rate of an API to a specific therapeutic need
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
