title: pH-independent immediate release polymethacrylate formulations--an observational study.
abstract: Using Eudragit® E PO (EudrE) as a polymethacrylate carrier, the aim of the study was to develop a pH-independent dosage form containing ibuprofen (IBP) as an active compound via chemical modification of the polymer (i.e. quaternization of amine function) or via the addition of dicarboxylic acids (succinic, glutaric and adipic acid) to create a pH micro-environment during dissolution. Biconvex tablets (diameter: 10 mm; height: 5 mm) were produced via hot melt extrusion and injection molding. In vitro dissolution experiments revealed that a minimum of 25% of quaternization was sufficient to partially (up to pH 5) eliminate the pH-dependent effect of the EudrE/IBP formulation. The addition of dicarboxylic acids did not alter IBP release in a pH 1 and 3 medium as the dimethyl amino groups of EudrE are already fully protonated, while in a pH 5 solvent IBP release was significantly improved (cf. from 0% to 92% release after 1 h dissolution experiments upon the addition of 20 wt.% succinic acid). Hence, both approaches resulted in a pH-independent (up to pH 5) immediate release formulation. However, the presence of a positively charged polymer induced stability issues (recrystallization of API) and the formulations containing dicarboxylic acids were classified as mechanically unstable. Hence, further research is needed to obtain a pH-independent immediate release formulation while using EudrE as a polmethacrylate carrier.
authors.affiliation: a Laboratory of Pharmaceutical Technology and.
authors.forename: Bart
authors.initials: B
authors.lastname: Claeys
authors.affiliation: a Laboratory of Pharmaceutical Technology and.
authors.forename: Reinout
authors.initials: R
authors.lastname: Vandeputte
authors.affiliation: b Biopharmaceutical Technology Unit , Department of Pharmaceutics, Ghent University , Ghent , Belgium.
authors.forename: Bruno G
authors.initials: BG
authors.lastname: De Geest
authors.affiliation: a Laboratory of Pharmaceutical Technology and.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: a Laboratory of Pharmaceutical Technology and.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D002626:Chemistry, Pharmaceutical; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D011109:Polymethacrylic Acids / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C030613:polymethacrylic acid
keywords: Drug delivery; extrusion; immediate release; injection molding; polymers