The vulnerability of controlled release formulations when co-ingested with alcohol represents a current major concern of regulatory agencies. Dose dumping might occur when drugs and/or excipients exhibit higher solubility in ethanolic solutions compared to water. In this study, xanthan gum was chosen as rate-controlling polymer for the development of alcohol resistant matrix formulations and theophylline as model drug. Two polymer particle sizes (75 and 180μm) and concentrations (30 and 60% w/w) were used to assess their influence on the in-vitro drug release from directly compressed tablets and mini-tablets, in 0% and 40% ethanol for 2h (pH 1.2). For both, tablets and mini-tablets, by using 60% xanthan gum similar dissolution profiles in hydrous and hydroalcoholic media were obtained, independently of the polymer particle size. By decreasing the polymer concentration a risk of alcohol-induced dose dumping was recognised, however only when larger polymer particles were used. In particular, mini-tablets underwent disintegration and released the entire dose within 5min in alcohol. Nevertheless, finer polymer particles used at lower concentration led to the formation of a more coherent and less porous gel layer and alcohol resistance could be tailored in regard to both matrix tablets and mini-tablets.
Keywords: Alcohol-induced dose dumping; Direct compression; Matrix tablet; Mini-tablet; Swelling; Xanthan gum.
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