Sustained-release pellets prepared by combination of wax matrices and double-layer coatings for extremely water-soluble drugs.
This study was performed in order to develop a sustained-release pellet formulation containing venlafaxine hydrochloride (VEN), an extremely water-soluble drug, prepared by combination of wax matrices and double-layer coatings. The influence of both double-layer polymeric coats and wax matrices on the release of VEN from sustained-release pellets was investigated. The pellets were prepared by wet mass extrusion spheronization methods and then coated with a fluidized bed coater. For the pellets coated with Eudragit NE30D alone, a coating level of nearly 40% was required to pass the dissolution test compared with commercial product, and it was accompanied by an unacceptable lag time. The application of an alcohol-soluble polymeric subcoat, Opadry I, was added before the Eudragit NE30D coating process, which resulted in a marked delay in drug release. However, a faster release was observed for the formulation coated with a high subcoat level (10%) at the end of the dissolution test. A further delay in drug release was observed when a wax matrix, octadecanol, was added to the core pellet formulation. The kinetics of drug release changed from the Higuchi model to a zero order model and the predominant mechanism controlling drug release changed from diffusion to dissolution upon increasing the amount of octadecanol within the matrix pellets. In addition, the drug release was markedly influenced by the drug to matrix ratio. In conclusion, the 40% drug-loaded core pellets with double-layer coatings (8% Opadry I and 12% Eudragit NE30D) and 20% octadecanol matrix produced the desired profile for once-daily sustained release compared with the commercial product, and these pellets remained stable during storage.
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Lingling
L
Tian
Yu
Y
Zhang
Xing
X
Tang
D000928:Antidepressive Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003511:Cyclohexanols / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D005233:Fatty Alcohols / Q000737:chemistry*; D007700:Kinetics; D008689:Methacrylates / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013696:Temperature; D000069470:Venlafaxine Hydrochloride; D014885:Waxes / Q000737:chemistry
D000928:Antidepressive Agents; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; C477853:Eudragit NE 30-D; D005079:Excipients; D005233:Fatty Alcohols; D008689:Methacrylates; D011108:Polymers; D013608:Tablets, Enteric-Coated; D014885:Waxes; D000069470:Venlafaxine Hydrochloride