The effect of alcohol on ionizing and non-ionizing drug release from hydrophilic, lipophilic and dual matrix tablets

Václav Lochař; Alena Komersová; Kevin Matzick; Barbora Slezáková; Martin Bartoš; Jitka Mužíková; Samir Haddouchi

doi:10.1016/j.jsps.2019.11.020

The effect of alcohol on ionizing and non-ionizing drug release from hydrophilic, lipophilic and dual matrix tablets

Saudi Pharm J. 2020 Feb;28(2):187-195. doi: 10.1016/j.jsps.2019.11.020. Epub 2019 Dec 7.

Authors

Václav Lochař¹, Alena Komersová¹, Kevin Matzick¹, Barbora Slezáková¹, Martin Bartoš², Jitka Mužíková³, Samir Haddouchi⁴

Affiliations

¹ Department of Physical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 95, 532 10 Pardubice, Czech Republic.
² Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 95, 532 10 Pardubice, Czech Republic.
³ Department of Pharmaceutical Technology, Charles University, Faculty of Pharmacy in Hradec Králové, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
⁴ SPS Pharma Services, 3 Rue Châteaubriand, 45071 Orléans, France.

Abstract

The aim of this work was to investigate and quantitatively evaluate the effect of presence of alcohol on in vitro release of ionizing and non-ionizing drug from hydrophilic, lipophilic and hydrophilic-lipophilic matrix tablets. The Food and Drug Administration (FDA) recommends in vitro dissolution testing of extended release formulations in ethanolic media up to 40% because of possible alcohol-induced dose dumping effect. This study is focused on comparison of the dissolution behavior of matrix tablets (based on hypromellose and/or glyceryl behenate as retarding agent) of the same composition containing different type of drug - ionizing tramadol hydrochloride (TH) and non-ionizing pentoxifylline (PTX). The dissolution tests were performed in acidic medium (pH 1.2) and in alcoholic medim (20%, 40% of ethanol) and the changes of tablets were observed also photographically. It was found that the alcohol resistence of the hydrophilic-lipophilic formulations with TH and the hydrophilic-lipophilic formulations with PTX containing a higher amount of hypromellose does not reflect the alcohol resistence of the formulations with pure hypromellose or glyceryl behenate. Both hydrophilic-lipophilic formulation with TH and more lipophilic formulation with PTX show significant alcohol dose dumping effect.

Keywords: Alcohol; Dissolution; Glyceryl behenate; Hypromellose; Pentoxifylline; Tramadol hydrochloride.