title: Effect of synthesis parameters of the sol-gel-processed spray-dried silica gel microparticles on the release rate of dexmedetomidine.
abstract: The objective of this study was to evaluate the possibilities to control the release rate of dexmedetomidine (DMED) from different spray-dried silica gel microparticle formulations. Microparticles were prepared by spray drying a silica sol polymer solution containing the drug. Drug release was investigated both in vitro and in vivo. The influence of sol-gel synthesis parameters, like pH and the water/alkoxide ratio (r) of the sol, on the release behaviour of the drug was studied. Silica gel microparticles had a smooth surface. Microparticles prepared from diluted sol, however, were more aggregated and clustered. The drug release conformed to zero order release from microparticles prepared near the isoelectric point of silica (pH 2.3 and pH 3) and to the square root of time kinetics from microparticles prepared at pH 1 and pH 5. The release also showed a dual-phasic profile with an initial burst and after that a slower release period. The dexmedetomidine release conformed to zero order kinetics from microparticles prepared at water/ alkoxide ratios between r = 6 and r = 35 (at pH 2.3). The release rate was the slowest from microparticles prepared with water/ alkoxide ratio 35. The bioavailability of dexmedetomidine in dogs showed that the release was sustained from silica gel microparticles as compared with a subcutaneously administered reference dose of 0.1 mg.
authors.affiliation: Pharmaceutical Development Department, Orion Corporation, Turku, Finland. pirjo.kortesuo@leiras.fi
authors.forename: Pirjo
authors.initials: P
authors.lastname: Kortesuo
authors.forename: Manja
authors.initials: M
authors.lastname: Ahola
authors.forename: Minna
authors.initials: M
authors.lastname: Kangas
authors.forename: Mika
authors.initials: M
authors.lastname: Jokinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Leino
authors.forename: Lauri
authors.initials: L
authors.lastname: Vuorilehto
authors.forename: Sirpa
authors.initials: S
authors.lastname: Laakso
authors.forename: Juha
authors.initials: J
authors.lastname: Kiesvaara
authors.forename: Antti
authors.initials: A
authors.lastname: Yli-Urpo
authors.forename: Martti
authors.initials: M
authors.lastname: Marvola
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D006863:Hydrogen-Ion Concentration; D007526:Isoelectric Point; D007700:Kinetics; D008297:Male; D011108:Polymers / Q000737:chemistry; D058428:Silica Gel; D012822:Silicon Dioxide / Q000737:chemistry*; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D018712:Analgesics, Non-Narcotic; D011108:Polymers; D014867:Water; D058428:Silica Gel; D020927:Dexmedetomidine; D012822:Silicon Dioxide