Leakage of enteric (Eudragit® L)-coated dosage forms in simulated gastric juice in the presence of poly(ethylene glycol)

被引:17
作者
Breitkreutz, J [1 ]
机构
[1] Univ Munster, Inst Pharmaceut Technol, D-48149 Munster, Germany
关键词
drug interaction; poly(methacrylic acid); poly(ethylene glycol); coatings; gastric juice resistance;
D O I
10.1016/S0168-3659(00)00197-8
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Poly(methacrylic acid) (PMAA) and related copolymers strongly interact with poly(ethylene glycol) (PEG) in acidic fluids. Due to the in vitro experiments presented in this paper, there is a clear indication for a drug-drug interaction in vivo between PEG solutions, e.g., commercially available laxatives, and dosage forms with PMAA-based enteric-coatings (Eudragit L). In these studies, enteric-coated tablets did not fulfil the pharmacopoeias' criteria of the disintegration test if PEGs were present in the simulated gastric juice. Drug substances which are known to be unstable in acidic media or which can cause gastric irritation were released from their enteric-coated dosage forms in acidic PEG media (pH 1). Various drug dosage forms, single and multiple unit systems, were tested. They show higher and faster drug release in the presence of PEG. To get insight into the mechanism of the interaction, experiments and theoretical calculations were performed which reveal that PEGs with high molecular weight show stronger interactions with PMAA coatings indicating a contribution of hydrophobic interactions to the occurring intermolecular forces. Hydrogen bonds can be build between each monomeric unit of PEG and the acidic sequences of the copolymer. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:79 / 88
页数:10
相关论文
共 27 条
[1]  
[Anonymous], 1989, AQUEOUS POLYM COATIN
[2]  
BAGLEY EB, 1971, J PAINT TECHNOL, V43, P35
[3]  
BAUER KH, 1988, UBERZOGENE ARZNEIFOR
[4]   LEACHING OF WATER-SOLUBLE PLASTICIZERS FROM POLYMERIC FILMS PREPARED FROM AQUEOUS COLLOIDAL POLYMER DISPERSIONS [J].
BODMEIER, R ;
PAERATAKUL, O .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 1992, 18 (17) :1865-1882
[5]   Prediction of intestinal drug absorption properties by three-dimensional solubility parameters [J].
Breitkreutz, J .
PHARMACEUTICAL RESEARCH, 1998, 15 (09) :1370-1375
[6]  
BREITKREUTZ J, 1996, THESIS AACHEN
[7]   MISCIBILITY PREDICTION BASED ON THE CORRESPONDING STATES THEORY - POLY(ETHYLENE OXIDE) ATACTIC POLY(METHYL METHACRYLATE) SYSTEM [J].
CIMMINO, S ;
MARTUSCELLI, E ;
SILVESTRE, C .
POLYMER, 1989, 30 (03) :393-398
[8]  
FROMMING KH, 1975, ARZNEIMITTEL-FORSCH, V25, P1958
[9]   The use of solubility parameters in pharmaceutical dosage form design [J].
Hancock, BC ;
York, P ;
Rowe, RC .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1997, 148 (01) :1-21
[10]  
HEALEY JNC, 1989, DRUG DELIVERY GASTRO, P83