A novel skeletal drug delivery system using self-setting calcium phosphate cement. 7. Effect of biological factors on indomethacin release from the cement loaded on bovine bone.
The use of self-setting bioactive calcium phosphate cement containing indomethacin as a model drug in bovine bone was investigated by means of an in vitro drug release test, mercury porosimetry, and scanning electron microscopy (SEM). Calcium phosphate cements containing 2 and 5% indomethacin after being mixed with dilute phosphoric acid were applied to defect sites and the medullary cavity of bovine bone and transformed into hydroxyapatite. The in vitro drug release from the cement loaded on the defect site into a simulated body fluid (SBF) containing 2.5 mM Ca2+ and 1.0 mM HPO4(2+) or 0.1 M phosphate buffer at pH 7.25 and 37 degrees C continued for more than 3 weeks. The release profiles of the drug-loaded cements in phosphate buffer were linear using the Higuchi plot; however, that was not the case for SBF. The drug release in SBF was much lower than that in phosphate buffer. The total pore volume of the cement after the drug release test in SBF was lower than its initial value. However, the pore size of 0.1-0.01 microns after drug release in phosphate buffer was higher than that seen in SBF. The micropore distribution results suggested that hydroxyapatite crystallized from SBF and the pore volume in the cement decreased after drug release. However, in phosphate buffer it appeared to dissolve. The SEM observations for cements loaded on the bone after drug release in phosphate buffer suggested that there was a boundary layer between the cement and natural bone, but this was not the case in SBF, where the cement bonded with the natural bone. The drug release rates from the cement-loaded bone were significantly higher than those from cement loaded on the dissolution holder. The results suggested that cement formation and drug release were affected by the presence of protein from natural bone. The drug release rates from the cement loaded on the defective bone were slower than those from the medullary cavity.
Otsuka
M
M
Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Japan.
Nakahigashi
Y
Y
Matsuda
Y
Y
Fox
J L
JL
Higuchi
W I
WI
D000818:Animals; D001843:Bone Cements / Q000737:chemistry; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002130:Calcium Phosphates / Q000737:chemistry; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D006882:Hydroxyapatites; D007213:Indomethacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D012995:Solubility
D001843:Bone Cements; D002130:Calcium Phosphates; D006882:Hydroxyapatites; D007213:Indomethacin