The in vitro and in vivo indomethacin release from self-setting bioactive glass bone cement

Article type: Research Article

Authors: Otsuka, Makoto^; | Nakahigashi, Yoshinori | Matsuda, Yoshihisa | Kokubo, Tadashi | Yoshihara, Satoru | Fujita, Hiroshi | Nakamura, Takashi

Affiliations: Departmenf of Pharmaceutical Technology, Kobe Pharmaceutical University, Higashi-Nada, Kobe 658, Japan | Faculty of Engineering, Kyoto University, Sakyo, Kyoto 606-01, Japan | Nippon Electric Glass Co., Ohtsu 520, Japan | Faculty of Medicine, Kyoto University, Sakyo, Kyoto 606, Japan

Note: [] Correspondence to: Makoto Otsuka, Ph.D., Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyama-Kitamachi, Higashi-Nada, Kobe 658, Japan. Tel.: +81 78 441 7531; Fax: +81 78 441 7532; E-mail: m-otsuka@kobepharma-u.ac.jp.

Abstract: The in vivo and in vitro drug release profiles from a self-setting bioactive CaO-SiO2-P2O5 glass bone cement containing indomethacin as a model drug were investigated. The cement containing 2% and 5% indomethacin (IMC) powder hardened within 5 min after mixing with ammonium phosphate buffer. After setting, in vitro drug release from drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37°C continued for two weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite during the drug release test in SBF. An IMC-loaded cement device (2% and 5% drug) was implanted in the subcutaneous tissue on the back of rats. The in vivo IMC release from the cement increased and attained maximum levels (Cmax of 2% and 5% drug-loaded cements was 0.27 and 3.37 μg/ml, respectively) at Tmax, 3 and 0.5 d, respectively, upon subcutaneous (s.c.) administration in rats. This suggested that the s.c. administration of the cement provided IMC release for a much longer period than s.c. administration of the solution, and the plasma IMC concentration was dependent on the drug concentration in the cement. The plasma IMC concentration and the area under the curve from 2% and 5% IMC-Ioaded cements in rats were dependent on the concentration of IMC in the cements. The in vivo IMC concentration in plasma obtained by the deconvolution method was much lower than that delivered in SBF in vitro. Scanning electron microscopy and photomicrographs of cross sections showed that the bioactive bone cement had excellent biocompatibility with the surrounding soft tissues.

Keywords: Hydroxyapatite, biomaterial, artificial bone, self-setting bone cement, bioactive bone glass cement, a drug delivery system for skeletal tissue, in vivo drug release test

DOI: 10.3233/BME-1997-7502

Journal: Bio-Medical Materials and Engineering, vol. 7, no. 5, pp. 291-302, 1997