Alkyl-substituted silica gel as a carrier in the controlled release of dexmedetomidine.
The effect of alkyl substitution of the silica xerogel matrix on the release rate of dexmedetomidine was evaluated. Silica sol was processed by either casting or spray drying. When the reaction precursor tetraethylorthosilicate (TEOS) was partially substituted with tri- or dialkoxysilane, the release of dexmedetomidine and degradation of the matrix were decreased compared with 100% TEOS-based gel. Increasing the number or length of the organic groups attached to silicon, modified the silica gel structure and reduced the release rate of dexmedetomidine from monoliths. The release of dexmedetomidine from alkyl-substituted silica gel microparticles, however, showed a burst in drug release. Subcutaneously administered silica xerogel matrices (manufactured by casting, containing 25 mol% dimethyldiethoxysilane at two different doses of dexmedetomidine) were studied in dogs. Sustained delivery of dexmedetomidine was obtained for at least 48 h.
Kortesuo
P
P
Orion Corporation Orion Pharma, P.O. Box 425, FIN-20101, Turku, Finland. pirjo.kortesuo@orionpharma.com
Ahola
M
M
Kangas
M
M
Leino
T
T
Laakso
S
S
Vuorilehto
L
L
Yli-Urpo
A
A
Kiesvaara
J
J
Marvola
M
M
D000478:Alkylation; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D003692:Delayed-Action Preparations; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004285:Dogs; D004337:Drug Carriers; D004343:Drug Implants; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D058428:Silica Gel; D012822:Silicon Dioxide; D012995:Solubility
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D058428:Silica Gel; D020927:Dexmedetomidine; D012822:Silicon Dioxide