A novel skeletal drug delivery system using a self-setting calcium phosphate cement. 5. Drug release behavior from a heterogeneous drug-loaded cement containing an anticancer drug.
A novel drug delivery device based on a self-setting bioactive calcium phosphate cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro using the anticancer agent 6-mercaptopurine (6-MP) as a model compound. X-ray diffraction results suggest that equimolar mixtures of the calcium phosphate salts were transformed into hydroxyapatite after being mixed with a dilute phosphoric acid solution, even in the presence of various amounts of 6-MP powder. The inclusion of 6-MP in the reaction mixture resulted in the formation of a homogeneous drug-containing cement. Alternatively, the drug was loaded after cement formation to produce a heterogeneous drug-containing pellet. In vitro drug release from both the homogeneous and heterogeneous drug-loaded cement pellets into simulated body fluid (pH 7.25, 37.0 degrees C) was measured using the rotating-disk method. Release from the homogeneous 5% drug-loaded cements did not obey the Higuchi equation. The release rate from the heterogeneous drug-loaded cements of different thicknesses (1, 2, and 3 mm) was a function of thickness, indicating that release kinetics could be controlled by the design of the cement formulation.
Otsuka
M
M
Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Japan.
Matsuda
Y
Y
Suwa
Y
Y
Fox
J L
JL
Higuchi
W I
WI
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001843:Bone Cements / Q000737:chemistry; D001842:Bone and Bones / Q000378:metabolism*; D002130:Calcium Phosphates / Q000737:chemistry; D016503:Drug Delivery Systems; D006882:Hydroxyapatites; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers; D012995:Solubility; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D001843:Bone Cements; D002130:Calcium Phosphates; D006882:Hydroxyapatites; D011108:Polymers; D015122:Mercaptopurine