Release behavior of VAN from four types of CaP-ceramic granules using various loading methods at two different degrees of acidity

Abstract

The release behavior of vancomycin (VAN) from beta-tricalciumphosphate (βTCP), hydroxyapatite (HA), glass ceramic (GC) and sponge-like collagen βTCP granule composite (sponge) was studied. Vacuum and drip loading methods were compared. The influence of VAN concentration and pH on release behavior was analyzed with respect to a stable release level of VAN above the minimum inhibitory concentration over 14 days. Initially the morphology of the granule carrier systems was examined with ESEM, stereomicroscopy, µCT-imaging and Camsizer® regarding porosity, interconnecting pores and granule size. Drug release patterns following a vacuum and a drip loading method with VAN at concentrations of 5 and 50 mg/ml were compared. The influence of pH 7.4 compared to pH 5.0 on release behavior was studied. The drug was released in bidistilled water at 37 °C, the concentration determined by photometry at 220 nm. For statistical purposes, the mean and standard deviation were calculated and analyzed by Origin 9.1 Professional SR1 (OriginLab). Due to low interconnectivity and low porosity, the vacuum loading method was unable to attain complete drug loading of the ceramic granules. The sponge showed an inhomogeneous distribution of βTCP granules. Drug release was high at pH 7.4, at pH 5.0 it practically did not occur. All samples except for the collagen-complex show an initial VAN burst release with a following steady release. Loading with 5 mg/ml concentrated VAN resulted in a higher percentage of available drug being released. However, when loaded with 50 mg/ml, the absolute amount of drug released was higher.

Graphical abstract

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