AIM: To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively. METHODS: DS tablets and 5-ASA pell...AIM: To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively. METHODS: DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit L100 and $100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied. RESULTS: Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium, but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets, 5-ASA release was significantly governed by pH. Moreover, the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit~ L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release. CONCLUSION: Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.展开更多
Aim To explore interaction mode between amphoteric molecules with the orderedphospholipid membrane. Methods Membrane interactions were determined by immobilized artificialmembrane (IAM) chromatography and solutes'...Aim To explore interaction mode between amphoteric molecules with the orderedphospholipid membrane. Methods Membrane interactions were determined by immobilized artificialmembrane (IAM) chromatography and solutes' hydrophobicity was measured by n-octanol/buffer system.Results The ampholytes, similar to bases, generally exhibited higher membrane affinity than expectedfrom their hydrophobicity, resulting from the attractive polar interaction with phospholipidmembrane. Furthermore, the strength of additional polar interaction with membrane (Δlg k_(IAM)) wasthen calculated. The Δlg k_(IAM) values were far greater for bases and ampholytes ranging from0.50 - 1.39, than those for acids and neutrals with the scope from - 0.55 - 0.44. ConclusionConsidering the microspecies distribution of amphoteric molecules, it was assumed that not onlyneutral and positive but also zwitterionic microspecies are capable of partitioning into orderedamphoteric lipid membrane with complementarily conformational and energetically favorableinteractions.展开更多
基金SuppoSed by the Foundation of Ministry of Education of China for distinguished Teachers,No.903 and the Natural Science Foundation of Liaoning Province,No.9910500504
文摘AIM: To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively. METHODS: DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit L100 and $100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied. RESULTS: Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium, but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets, 5-ASA release was significantly governed by pH. Moreover, the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit~ L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release. CONCLUSION: Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.
文摘Aim To explore interaction mode between amphoteric molecules with the orderedphospholipid membrane. Methods Membrane interactions were determined by immobilized artificialmembrane (IAM) chromatography and solutes' hydrophobicity was measured by n-octanol/buffer system.Results The ampholytes, similar to bases, generally exhibited higher membrane affinity than expectedfrom their hydrophobicity, resulting from the attractive polar interaction with phospholipidmembrane. Furthermore, the strength of additional polar interaction with membrane (Δlg k_(IAM)) wasthen calculated. The Δlg k_(IAM) values were far greater for bases and ampholytes ranging from0.50 - 1.39, than those for acids and neutrals with the scope from - 0.55 - 0.44. ConclusionConsidering the microspecies distribution of amphoteric molecules, it was assumed that not onlyneutral and positive but also zwitterionic microspecies are capable of partitioning into orderedamphoteric lipid membrane with complementarily conformational and energetically favorableinteractions.
