Study On Drug Release Kinetics From Tetracycline Hydrochloride/α-TCP Bone Cement And In Vitro Dissolution Kinetics Of α-TCP Bone Cement

Calcium phosphate cements (CPC) are used for bone defect filling and may also be used as delivery systems for active agents. In the present PhD dissertation, hydration property of Tetracycline Hydrochloride (TTCH) / a-tricalcium phosphate (a-TCP) bone cement, and its drug release kinetics, dissolution kinetics and surface and interfacial energy parameters of hardened body have been studied.The hydration of a-TCP is not prevented by TTCH, but setting time of CPC is prolonged with the increase in added amount of TTCH. Compressive strength of the cement hardened body with certain amount of TTCH is higher than that of without, but too much can do harm to its compressive strength. The strengthening structure may be related with the change in morphology of apatite crystals and the formation of a polymeric network between the entangled crystals of apatite.Released antimicrobial agents from setted a-TCP cements with different content of TTCH immersed in static physiological saline(PS) at 37C can sustain over 8 weeks, and release profile of the cements vary depending on the content of TTCH added, which resulted from a strong affinity for adsorption of TTCH on calcium phosphates. It has been showed that TTCH release was controlled by two mechanisms: (1) diffusion of free TTCH molecules through the porous cement(square-root-of-time kinetics), namely Higuchi model; and (2) dissociation of TTCH from the apatite-TTCH complex (zero-order kinetics). The first mechanism was predominant in high concentration TTCH-loaded apatite cement systems, whereas for low content TTCH-loaded apatite cements system at later release stage, the second mechanism becomes important at later release times. In dynamic release media, drug release from drug-loaded cements in PS is similar to that in static media, but not the case for the simulated body fluid (SBF). The drug release in SBF was much lower than that in PS, and is according to Higuchi model only at initial stage because of forming hydroxyapatite(HA) precipitate in SBF. When TTCH-loaded a-TCP cements were cured by water vapour, the rate of drug release is much lower compared with that without.In PS, the existence of individual Ca2+ and HPO42" has no influence on the drug release rate from TTCH-loaded cement, and the existence of HPO42" does almost the same in SBF. However existence of Ca2+ individual in SBF will decrease the release rate of TTCH. On the other hand, it is also showed that Ca2+ in solution has no influence on TTCH adsorption and precipitation on apatite surface, even if Ca2+will precipitate on apatite surface accompanied chelated TTCH.Dissolution process of a-TCP cement hardened body accords with the kinetic model equation: y = -ln(l-x) =kt05 , its activation energy is 9.87 kJ/mol, which means dissolution is diffusion control. The dissolution mechanism of a-TCP cement may be considered as dissolution and reprecipitation of defective calcium hydroxy- apatite (CDHA) hydrated from a-TCP. It has been shown that dissolution process of TTCH-loaded a-TCP cement accords with kinetic model equation: y = -ln(l-x) =kt04, and dissolution activation energy of a-TCP cement hardened body with 1% (w/w) TTCH is about 7.17kJ/mol, however the dissolution rate constant decreases with increasing the content of TTCH.The contact angles of liquids with a-TCP cement hardened body change when TTCH is added in, but almost does not change after content of TTCH is over l%(w/w). The measurement and calculation of interface intension of a-TCP cementhardened body with water indicate that addition of TTCH results in the increasing hydrophobicity and the interface intension of apatite surface with water.