Formulation and thermal sterile stability of a less painful intravenous clarithromycin emulsion containing vitamin E

The purpose of this study is to develop a less painful intravenous clarithromycin emulsion (ClaE) and investigate its thermal sterile stability. The formulation of ClaE is composed of clarithromycin 0.25% (w/v), vitamin E 5% (w/v), medium chain triglyceride (MCT) 10% (w/v), egg lecithin 1.0% (w/v), Cremophor EL-40 (EL-40) 2% (w/v), Pluronic F-68 (F-68) 0.2% (w/v), Tween80 0.2% (w/v), glycerol 2.5% (w/v) and l-cysteine 0.05% (w/v) in water. High-pressure homogenization, photon correlation spectroscopy (PCS) and electrophoretic light scattering (ELS) technology, light microscopy and high-performance liquid chromatography (HPLC) methods were used in the preparation and evaluation of ClaE. Investigation of thermal sterile stability included the effects of different thermal sterile methods, thermal sterile time, drug concentrations and pH values. Sterilization in a 100 °C rotating water bath for 30 min was finally adopted as the sterilization method. The drug remaining was 98.6% and 96.5%, respectively, before and after thermal sterilization. Moreover, the pH value, particle size distribution (PSD), ζ-potential and entrapment efficiency (EE) of ClaE after sterilization were 7.95, 213.6 nm, −22.29 mV and 96.35%, respectively. This showed that ClaE had sufficient physicochemical stability to resist the sterilization process. Tests using animal models demonstrated that there was a marked pain reduction following the injection of ClaE compared with clarithromycin solution. Overall, ClaE described in this paper may be very suitable for industrial-scale production and clinical application.