Coatings of Eudragit® RL and L-55 Blends: Investigations on the Drug Release Mechanism.
In a previous study, generally lower drug release rates from RL:L55 blend coated pellets in neutral/basic release media than in acidic release media were reported. The aim of this study was to obtain information on the drug release mechanism of solid dosage forms coated with blends of Eudragit® RL (RL) and Eudragit® L-55 (L55). Swelling experiments with free films were analyzed spectroscopically and gravimetrically to identify the physicochemical cause for this release behavior. With Raman spectroscopy, the swelling of copolymer films could be monitored. IR spectroscopic investigations on RL:L55 blends immersed in media at pH 6.8 confirmed the formation of interpolyelectrolyte complexes (IPECs) that were not detectable after swelling in hydrochloric acid pH 1.2. Further investigations revealed that these IPECs decreased the extent of ion exchange between the quaternary ammonium groups of RL and the swelling media. This is presumably the reason for the previously reported decreased drug permeability of RL:L55 coatings in neutral/basic media as ion exchange is the determining factor in drug release from RL coated dosage forms. Gravimetric erosion studies confirmed that L55 was not leached out of the film blends during swelling in phosphate buffer pH 6.8. In contrast to all other investigated films, the 4:1 (RL:L55) blend showed an extensive swelling within 24 h at pH 6.8 which explains the reported sigmoidal release behavior of 4:1 blend coated pellets. These results help to understand the release behavior of RL:L55 blend coated solid dosage forms.
Department of Chemistry, Division of Pharmaceutical Technology, University of Hamburg, Bundesstr. 45, 20146, Hamburg, Germany.
Robert
R
Wulff
Department of Chemistry, Division of Pharmaceutical Technology, University of Hamburg, Bundesstr. 45, 20146, Hamburg, Germany. Claudia.Leopold@Uni-Hamburg.de.
Claudia S
CS
Leopold
D004304:Dosage Forms; D004343:Drug Implants / Q000737:chemistry; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*
D004304:Dosage Forms; D004343:Drug Implants; D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C058665:Eudragit RL; D006851:Hydrochloric Acid
enteric polymethacrylate; interpolyelectrolyte complex; ion exchange; polymer blend; quaternary polymethacrylate