Preparation and in vitro and in vivo study on tinidazole in situ forming sustained-release injection / 药学学报

ABSTRACT

This study is to prepare the in situ forming sustained-release injection which can perform sustained release behavior at the periodontal site for 7 days and to evaluate its in vitro and in vivo properties. After preparation of in situ forming sustained-release injection the in situ time was studied. And the surface of the solid injection was characterized by SEM. The rheological curve at 0 degrees C, 25 degrees C, 37 degrees C was determined and the impact of the temperature on the viscosity was examined. The in vitro release behavior was investigated. At last, rabbit periodontitis model was established to study its pharmacokinetics. The injection was stable, hard to stratify and decompose. The in situ forming time was about 6 seconds. It can easily adhere into periodontal pockets. There were lots of holes on the surface of the solid injection for the drug to diffuse. The drug releasing curves could be fit by Korsmeyer-Peppas equation. The drug smoothly released for 7 days at pH 7.4 PBS buffer with a very slight burst release and maintained a certain concentration. In vivo pharmacokinetics results indicated that after administration with the in situ forming injection, achievement of tinidazole (TNZ) concentration in gingival crevicular fluid (GCF) was more comparable and long-lasting than usual solution of TNZ management and relatively constant TNZ levels were attained until 168 h. All these results supported the prospect of tinidazole in situ forming sustained-release injection in clinical applications.