Design and Evaluation of an Osmotic Pump Tablet (OPT) for Chlorpromazine Using (SBE)7m-β-CD

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Abstract
Purpose. 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-β-cyclodextrin, (SBE)7m-β-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-β-CD was pH-independent, and was controlled by modulating the membrane thickness of the OPT. Another cyclodextrin, hydroxypropyl-β-cyclodextrin (HP-β-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-β-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-β-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.