A novel skeletal drug delivery system using self-setting calcium phosphate cement VIII: the relationship between in vitro and in vivo drug release from indomethacin-containing cement

Abstract

The relationship between in vitro and in vivo drug release from a self-setting bioactive calcium phosphate cement containing indomethacin (IMC) as a model drug was investigated. The in vitro IMC release rate from 1, 2 and 5% drug-loaded cement systems in simulated body fluid (SBF) at pH 7.25, 37°C increased with increase of drug concentration in the cement. The decreasing amount of calcium concentration in SBF during the drug release increased with increase of time. This was attributed to in vitro precipitation and/or growth of hydroxyapatite on the cement. The plasma IMC concentration and the area under the curve (AUC) from 1, 2 and 5% IMC-loaded cements after s.c. administration in rat depended on the loaded IMC concentration in the cements. The in vivo IMC release profiles from the cement were deconvoluted from the plasma IMC profiles after s.c. administration of IMC solution in rats. The relationship between in vitro release in SBF and the in vivo release profiles of 1, 2 and 5% IMC-loaded cements showed a straight line in the initial stage, but did not in the later stages.