Mechanisms controlling theophylline release from ethanol-resistant coated pellets.
OBJECTIVE
To elucidate the mass transport mechanisms controlling drug release from recently proposed, ethanol-resistant, polymeric film coatings.


METHODS
Theophylline matrix pellets were coated with ethylcellulose: guar gum blends. Drug release from single pellets and ensembles of pellets was measured in various release media. Changes in the systems' morphology, composition and mechanical properties were monitored using SEM, gravimetrical analysis and a texture analyzer. Based on the obtained experimental results a mechanistically realistic mathematical model was identified and used to quantitatively predict drug release from coated pellets in ethanol-free and ethanol-containing bulk fluids.


RESULTS
Drug diffusion though the intact polymeric film coatings is likely to be the dominant mass transport mechanism in the investigated systems, irrespective of the ethanol content in the surrounding environment. An appropriate solution of Fick's law could be used to quantitatively predict theophylline release from pellets coated with different ethylcellulose:guar gum blends at different coating levels. Importantly, independent experiments confirmed the theoretical predictions.


CONCLUSIONS
In silico simulations can help facilitating the optimization of the novel ethanol-resistant polymeric film coatings, avoiding time-consuming and cost-intensive series of trial-and-error experiments. The presence/absence of ethanol does not affect the underlying drug release mechanisms.
College of Pharmacy, Univ. Lille Nord de France, 3 Rue du Prof. Laguesse, 59006, Lille, France.
Y
Y
Rosiaux
C
C
Velghe
S
S
Muschert
R
R
Chokshi
B
B
Leclercq
F
F
Siepmann
J
J
Siepmann
D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003198:Computer Simulation; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry*; D005685:Galactans / Q000737:chemistry*; D008351:Mannans / Q000737:chemistry*; D008956:Models, Chemical; D053149:Plant Gums / Q000737:chemistry*; D013806:Theophylline / Q000008:administration & dosage*
D001993:Bronchodilator Agents; D004337:Drug Carriers; D005685:Galactans; D008351:Mannans; D053149:Plant Gums; D000431:Ethanol; C013517:ethyl cellulose; D002482:Cellulose; D013806:Theophylline; C007894:guar gum