Nanosuspension for parenteral delivery of a p-terphenyl derivative: Preparation, characteristics and pharmacokinetic studies

• H2, a novel synthesized p-terphenyl derivative, is a promising and potential anti-cancer drug.
• Two different methods: precipitation method and microfluidization method were combined to prepare nanosuspensions.
• Increased saturation solubility and accelerated dissolution velocity were achieved.
• The pharmacokinetics test indicated that nanosuspensions we prepared would improve the bioavailability of H2

Recently, nanosuspension technology has evolved into a mature drug delivery system, which can enhance the saturation solubility and dissolution velocity of poorly soluble drugs. In this study, nanosuspensions of a p-terphenyl derivative (H2) were prepared by combining microfluidization and precipitation method and transformed into dry powder by lyophilization. The resultant nanosuspensions had a mean particle size of 201.7 ± 5.87 nm and a zeta potential of −21.07 ± 0.57 mV. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analysis verified that the crystalline state of H2 was not transformed when it was prepared to nanosuspensions. An increased saturation solubility (1.46ug/ml) and accelerated dissolution velocity were achieved. The percent drug release of bulk H2 and H2 nanosuspension dried powder was 7.16% and 93.5% at 120 min point, respectively. The pharmacokinetic test in rats indicated that the area under plasma concentration-time curve (AUC0~∞) value of H2 nanosuspension (5.183 mg/L h) was about 5-fold higher than that of H2 solution (1.094 mg/L h). Additionally, the mean retention time (MRT) value of H2 nanosuspension (2.832 h) was significantly longer than that of H2 solution (0.997 h).

Preparation procedure of a p-terphenyl derivative nanosuspension.Figure optionsDownload as PowerPoint slide