Prediction of drug release from ethylcellulose coated pellets.
The aim of this study was to elucidate the underlying drug release mechanisms in pellets coated with aqueous ethylcellulose dispersion, providing long term stable drug release profiles and containing different types of starter cores. The systems were thoroughly characterized using mechanical analysis; the sensitivity of drug release to the osmolality of the release medium was measured; scanning electron microscopy and optical macroscopy were used to monitor the pellets' morphology and dimensions upon exposure to different media, and drug release was measured from single and ensembles of pellets as well as from thin, free films. All experimental results indicate that diltiazem HCl release from pellets coated with ethylcellulose containing small amounts of poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer is primarily controlled by drug diffusion through the intact polymeric membranes, irrespective of the type of starter core (consisting of microcrystalline cellulose or sugar, optionally coated with ethylcellulose). Importantly, the apparent diffusion coefficient of the drug in the macromolecular networks could easily be determined with thin free films and successfully be used to quantitatively predict the release rate from coated pellets. Thus, based on this knowledge and using the presented mathematical theories the development of new/ optimization of existing controlled drug delivery systems of this type can be significantly facilitated.
Muschert
S
S
College of Pharmacy, University of Lille, 3 Rue du Professeur Laguesse, France.
Siepmann
F
F
Leclercq
B
B
Carlin
B
B
Siepmann
J
J
D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004110:Diltiazem / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D008956:Models, Chemical; D011237:Predictive Value of Tests; D012995:Solubility
D003692:Delayed-Action Preparations; D004337:Drug Carriers; C013517:ethyl cellulose; D002482:Cellulose; D004110:Diltiazem