Anion-induced water flux as drug release mechanism through cationic Eudragit RS 30D film coatings.
The objective of this study was to investigate the anion-controlled drug release mechanism through the cationic coating polymer Eudragit RS 30 D as a function of the anion attraction toward the polymer's quarternary ammonium group (QAG), anion valence, and film composition. The mechanism was investigated by dissolution testing, determination of chloride ion exchange using ion chromatography, plasticizer leaching by means of differential scanning calorimetry, and water uptake by Karl Fischer titration. All experiments were performed on coated theophylline micro tablets or isolated films of various compositions using 0.01 M sodium nitrate, sodium sulfate, disodium succinate, sodium acetate, and succinic acid as dissolution media. The mechanism of drug release involved an immediate penetration of dissolution medium into the polymer followed by an instant exchange of chloride against the medium's anion species at completely different rates compared with the drug release. Dependent on the attraction of the anion toward the QAGs, a water flux was induced by back and forth exchanging anions. Strong attraction (nitrate, sulfate) resulted in a low water flux while weak attraction resulted in a high flux (acetate, succinic acid). The water flux increased at increasing number of QAGs. Plasticizer acted as a diluent in respect of the number of QAGs, thus higher plasticizer concentrations led to lower drug release.
Wagner
Karl G
KG
University of Tuebingen, Institute of Pharmacy, Department of Pharmaceutical Technology, Tübingen, Germany. karl.wagner@uni-tuebingen.de
Gruetzmann
Ronny
R
D000180:Acrylic Resins / Q000737:chemistry* / Q000493:pharmacokinetics*; D000838:Anions; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics; D013608:Tablets, Enteric-Coated; D014867:Water / Q000378:metabolism*
D000180:Acrylic Resins; D000838:Anions; D003692:Delayed-Action Preparations; D011108:Polymers; D013608:Tablets, Enteric-Coated; D014867:Water; C050528:Eudragit RS