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.
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