How to adjust desired drug release patterns from ethylcellulose-coated dosage forms.
The aim of this study was to provide an easy and efficient tool to adjust desired drug release kinetics from (aqueous) ethylcellulose-coated solid dosage forms and to better understand the underlying mass transport mechanisms. Pure ethylcellulose films are poorly permeable for many substances and can result in very low release rates for certain drugs from coated dosage forms, if the film coatings are completely formed and remain intact upon exposure to the release media. To increase the permeability of the polymeric membranes, different amounts of a water-soluble poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer (PVA-PEG graft copolymer) were added to an aqueous ethylcellulose dispersion (Aquacoat ECD). Importantly, the presence of only a low percentage of this hydrophilic copolymer significantly increased the resulting water uptake rate and extent, dry weight loss and drug permeability of the films. In contrast to hydroxypropyl methylcellulose (HPMC), the PVA-PEG graft copolymer does not cause flocculation of the colloidal coating dispersion (leading to potentially variable release rates). Interestingly, the transport of water as well as of the model drug theophylline through the polymeric networks was primarily controlled by pure diffusion. The penetration kinetics could be quantitatively described by Fick's law of diffusion, irrespective of the type of release medium and PVA-PEG graft copolymer content. Most important from a practical point of view, a broad spectrum of pH-independent drug release rates can easily be obtained from drug-loaded pellets by simply varying the PVA-PEG graft copolymer content. An appropriate curing step after coating is required, but interestingly the investigated curing conditions (differing in time and relative humidity) resulted in very similar drug release patterns, indicating that stable film structures are likely to be achieved.
Siepmann
F
F
College of Pharmacy, JE 2491, University of Lille, 3 Rue du Professeur Laguesse, 59006 Lille, France.
Hoffmann
A
A
Leclercq
B
B
Carlin
B
B
Siepmann
J
J
D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D011142:Polyvinyl Alcohol / Q000737:chemistry / Q000493:pharmacokinetics; D013608:Tablets, Enteric-Coated
D003692:Delayed-Action Preparations; D013608:Tablets, Enteric-Coated; D011092:Polyethylene Glycols; C013517:ethyl cellulose; D011142:Polyvinyl Alcohol; D002482:Cellulose