Drug release mechanisms from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

The aim of this study was to better understand the underlying drug release mechanisms from aqueous ethylcellulose-coated pellets containing different types of drugs and starter cores. Theophylline, paracetamol, metoprolol succinate, diltiazem HCl and metoprolol tartrate were used as model drugs exhibiting significantly different solubilities (e.g. 14, 19, 284, 662 and 800 mg/mL at 37 degrees C in 0.1N HCl). The pellet core consisted of a drug matrix, drug-layered sugar bead or drug-layered microcrystalline cellulose (MCC) bead, generating different osmotic driving forces upon contact with aqueous media. Importantly, the addition of small amounts of poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer (PVA-PEG graft copolymer) to the ethylcellulose coatings allowed for controlled drug release within 8-12h, irrespective of the type of drug and composition of the pellet core. Drug release was found to be controlled by diffusion through the intact polymeric membranes, irrespective of the drug solubility and type of core formulation. The ethylcellulose coating was dominant for the control of drug release, minimizing potential effects of the type of pellet core and nature of the surrounding bulk fluid, e.g. osmolality. Thus, this type of controlled drug delivery system can be used for very different drugs and is robust.