title: Design and evaluation of an osmotic pump tablet (OPT) for chlorpromazine using (SBE)7m-beta-CD.
abstract: OBJECTIVE
  The purpose of this study was to develop a controlled-porosity osmotic pump tablet (OPT) which exhibits pH-independent release profiles for a basic drug using a sulfobutyl ether-beta-cyclodextrin, (SBE)7m-beta-CD, which acts as both a solubilizer and as an osmotic agent.
  
  
  METHODS
  Chlorpromazine free base (CLP) was chosen as a model drug for this study. The release of CLP from osmotic pump tablets was studied in vitro. In vivo absorption of CLP from the OPT was evaluated in male beagle dogs.
  
  
  RESULTS
  The CLP release profile from an OPT prepared from a core tablet composed of a 1:10 molar ratio of CLP to (SBE)7m-beta-CD was pH-independent, and was controlled by modulating the membrane thickness of the OPT. Another cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and a sugar mixture of lactose and fructose resulted in pH-dependent release at the same molar ratio. An in vivo absorption study in dogs with an OPT containing (SBE)7m-beta-CD correlated very well with the in vitro release profiles using the Japanese Pharmacopoeia dissolution method.
  
  
  CONCLUSIONS
  In addition to serving as a solubilizer and osmotic agent, (SBE)7m-beta-CD can also serve as the controlling agent for pH independent release of CLP from OPTs. This system successfully modified the in vivo input rate of CLP without compromising oral bioavailability.
authors.affiliation: Technological Development Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Okimoto
authors.forename: A
authors.initials: A
authors.lastname: Ohike
authors.forename: R
authors.initials: R
authors.lastname: Ibuki
authors.forename: O
authors.initials: O
authors.lastname: Aoki
authors.forename: N
authors.initials: N
authors.lastname: Ohnishi
authors.forename: T
authors.initials: T
authors.lastname: Irie
authors.forename: K
authors.initials: K
authors.lastname: Uekama
authors.forename: R A
authors.initials: RA
authors.lastname: Rajewski
authors.forename: V J
authors.initials: VJ
authors.lastname: Stella
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000042:Absorption; D000818:Animals; D002746:Chlorpromazine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004285:Dogs; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D015195:Drug Design; D005632:Fructose / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007785:Lactose / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D009997:Osmotic Pressure; D012995:Solubility; D013607:Tablets; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D018492:Dopamine Antagonists; C103513:SBE7-beta-cyclodextrin; D013607:Tablets; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D005632:Fructose; D007785:Lactose; D002746:Chlorpromazine