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Objective: Extended release (ER) tablets/capsules in massive ingestion overdoses are prone to form pharmacobezoars potentially increasing the risk of late-appearing toxic effects and prolonged symptoms. Oral activated charcoal is often sufficient to prevent drug absorption, but in a recent massive ingestion of highly toxic substances, prior orogastric lavage might be considered. The disintegration characteristics of ER preparations in overdose situations is valuable to understand if the time line and course of the intoxication might be prolonged, but information on these characteristics are unavailable. Slow disintegration and/or pharmacobezoar formation, and the large size makes ER preparation impossible to evacuate using a 30F orogastric lavage tube. This study evaluates the disintegration and pharmacobezoar formation of a simulated massive ER tablet ingestion in an in vitro model, using a selection of extended release tablets, with different disintegrating characteristics when present in therapeutic numbers. Furthermore, the sizes of the formed pharmacobezoars were compared with the dimensions of a 30F orogastric lavage tube., Method: A standardized model mimicking the physical effects on pharmaceutical preparations in simulated gastric fluid (SGF) was developed and tested on three mono-depot ER tablets (quetiapine/Seroquel ® XR 50 mg, paracetamol/Pinex ® Retard 500 mg, verapamil/Isoptin ® Retard 240 mg), one poly-depot ER tablet (carbamazepine/Tegretol ® Retard 200 mg), and one immediate-release tablet (paracetamol/Panodil ® 500mg). Thirty tablets were placed in polyamide mesh bags, either together in one bag or in separate bags, immersed in 1 L SGF, and incubated at 37 °C for 48 h. Released drugs were quantified at 0.5-48 h., Results: Visual inspection showed that Seroquel ® XR, Pinex ® Retard, and Isoptin ® Retard tablets formed firm pharmacobezoars stable for more than 4 h and intact fractions remained for up to 24 h. Drug releases were reduced by 53%, 40%, and 31%, respectively, for up to 8 h compared to separated tablets. Light microscopy showed that contact with SGF transformed the coating of Seroquel ® XR and Pinex ® Retard to a diffusion-controlled swelled gel-layer, and the Isoptin ® Retard tablets into a rigid and slow-releasing matrix. Tegretol ® Retard disintegrated into microspheres within 30 min, and Panodil ® disintegrated within minutes., Discussion: The developed pharmacobezoars of mono-depot ER tablets demonstrated prolonged drug release. Neither the formed pharmacobezoars, nor the single tablets of the tested mono-depot ER preparations, would pass through the lumen of a standard orogastric lavage tube, rendering this modality ineffective for tablet removal in gastrointestinal decontamination.