Extrusion-spheronization of pH-sensitive polymeric matrix pellets for possible colonic drug delivery.
The aim of this study was to investigate extrusion-spheronization pelletization for preparing pH-sensitive matrix pellets for colon-specific drug delivery. The effects of three independent variables (amounts of Eudragit S, citric acid and spheronizing time) on pellet size, shape (roundness and aspect ratio), and drug release were studied with central composite design. The pellets contained ibuprofen as a model drug, citric acid as a pH-adjusting agent, Eudragit S as a pH-sensitive binder and microcrystalline cellulose (MCC). The pellets were prepared with Nica extrusion-spheronizing equipment and subsequently enteric-coated using an air-suspension technique. Eudragit S as a pH-sensitive matrix former in pellets increased the pellet size and influenced pellet roundness. In small amounts Eudragit S increased pellet roundness but in larger amounts pellet roundness was reduced. Citric acid promoted the pelletization process resulting in a narrower area distribution. The pH-sensitive matrix pellet failed to delay the drug release. The combination of citric acid and enteric coating, however, delayed the drug release for 15 min in a pH 7.4 phosphate buffer.
Krogars
K
K
Department of Pharmacy, Division of Pharmaceutical Technology, P.O. Box 56, FIN-00014 University of Helsinki, Finland. karin.krogars@helsinki.fi
Heinämäki
J
J
Vesalahti
J
J
Marvola
M
M
Antikainen
O
O
Yliruusi
J
J
D000180:Acrylic Resins; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019343:Citric Acid; D020099:Coated Materials, Biocompatible; D003106:Colon; D016503:Drug Delivery Systems / Q000379:methods*; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008853:Microscopy; D008863:Microspheres; D011108:Polymers; D011109:Polymethacrylic Acids; D012996:Solutions
D000180:Acrylic Resins; D020099:Coated Materials, Biocompatible; D005079:Excipients; D011108:Polymers; D011109:Polymethacrylic Acids; D012996:Solutions; C038300:methylmethacrylate-methacrylic acid copolymer; D019343:Citric Acid; D007052:Ibuprofen