Effect of SBE7-beta-cyclodextrin complexation on carbamazepine release from sustained release beads.
The effect of SBE7-beta-cyclodextrin together with hydroxypropylmethyl cellulose (HPMC) or polyvinylpyrrolidone (PVP) on the saturated solubility and delivery of carbamazepine (a poorly soluble drug) from sustained release (SR) beads was investigated. Carbamazepine solubility at room temperature increased from 0.1 to 5.4mg/ml by forming an inclusion complex with SBE7-beta-cyclodextrin (15%w/v). HPMC (0.1%w/v) also increased the aqueous solubility of carbamazepine, acting both alone and synergistically with SBE7-beta-cyclodextrin, to produce solubility values of 0.26 and 8.1mg/ml respectively. PVP (0.1-0.5%w/v) had no effect on carbamazepine solubility, either alone or in combination with SBE7-beta-cyclodextrin. The addition of SBE7-beta-cyclodextrin to SR beads increased the rate of carbamazepine release. In addition, comparable release rates where obtained when lower ratios of SBE7-beta-cyclodextrin together HPMC were incorporated in the SR bead. Therefore this ternary drug cyclodextrin polymer system was considered preferable over the binary drug cyclodextrin system for SR beads, as less cyclodextrin was required. However, both binary and ternary approaches were considered suitable techniques to improve the release rate and potentially the in vivo bioavailability of poorly soluble drugs that had previously exhibited slow or incomplete release from SR beads.
Smith
J S
JS
Pharmaceutical Research and Development, Pfizer Global Research and Development, Sandwich, UK. janet.s.smith@pfizer.com
Macrae
R J
RJ
Snowden
M J
MJ
D000465:Algorithms; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives; D011205:Povidone; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D047392:beta-Cyclodextrins / Q000737:chemistry*
D003692:Delayed-Action Preparations; D005079:Excipients; C103513:SBE7-beta-cyclodextrin; D047392:beta-Cyclodextrins; D002220:Carbamazepine; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D011205:Povidone