Solid state studies of drug-cyclodextrin inclusion complexes in PEG 6000 prepared by a new method.
The melting method was investigated as a possible method for producing drug-cyclodextrin (CD) inclusion compounds in a carrier. Various solid dispersions of alpha-, beta- and gamma-CD in polyethylene glycol (PEG) 6000 with and without the addition of 5% w/w indomethacin or griseofulvin were prepared using the original components. Characterisations of the samples included X-ray powder diffraction, modulated-temperature differential scanning calorimetry and dissolution tests by the paddle method according to USP XXI standard. Evidence of a complex between indomethacin and beta-CD in PEG 6000 was found. An indomethacin-gamma-CD complex formed a well defined phase in the PEG carrier, with tetragonal structure and unit cell parameters a=23.885(35) A and c=23.181(64) A. No complexation of indomethacin with alpha-CD, or with griseofulvin and beta-CD could be detected. It is suggested that competition between PEG and the drug for the binding to different CDs along with varying patterns of water loss from the CDs influence the inclusion reaction. The formation of complexes was accompanied by a decrease in the relative crystallinity of the dispersions. Dissolution tests showed that the CDs have a delaying effect on the release of indomethacin from PEG 6000 in the order alpha-CD<gamma-CD</=beta-CD.
Wulff
M
M
Department of Pharmaceutical Chemistry, Physical and Inorganic Chemistry, Box 574, Biomedical Center, Uppsala University, S-751 23, Uppsala, Sweden.
Aldén
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D006118:Griseofulvin / Q000737:chemistry*; D007213:Indomethacin / Q000737:chemistry*; D010592:Pharmaceutic Aids / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000935:Antifungal Agents; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010592:Pharmaceutic Aids; D006118:Griseofulvin; D011092:Polyethylene Glycols; D007213:Indomethacin