Studies On Tetracaine Hydrochloride Liposome Gel

Tetracaine hydrochloride was a common used local anesthetic.It was good at strength of penetration and diffusibility. It mainly used on endometrium quickly but it can’t stay long local anesthetic time. Because of its toxicity and these disadvantages, we hoped to develop a new dosage form with longer local anesthetic time and less disadvantages. We prepared tetracaine hydrochloride to liposome gel.The results suggested that the liposome gel be stabilizer than liposome, more convenient to patients and hold longer local anesthetic time and less disadvantages than tetracaine hydrochloride solution.Tetracaine hydrochloride was big dissolubility in water, which molecular Weight was 300.83 and pKa was 8.5.Due to alkalescence, we used ammonium sulfate gradient method to prepare tetracaine hydrochloride liposome. Liposomes and free drug were separated effectively by Sephadex-G-50 minicolumn centrifugation method. And orthogonal test was employed to optimize the conditions of preparation with entrapment efficiency of liposomes and appearance judgement. The optimum conditions for the preparation of liposomes were as follows:the ratio of lecithin to cholesterol was 4:1,the ratio of drug to lecithin was 1:14.4, the concentration of lecithin was 4% and the concentration of ammonium sulphate was 300mmol·L-1.The physicochemical properties of tetracaine hydrochloride liposome were studied. The liposome was spheroidal and uniform, the volume diameters of tetracaine hydrochloride liposome suspension was 170±23nm and entrapment efficiency reached 83.9%.After determining the kind of gel ground, we optimized the optimum conditions for preparing liposome gel by the quality of drug transdermal accumulative release at the rat skin. We optimize the conditions of preparation tetracaine hydrochloride liposome gel with 1%(w/w) carbopol 940,3%(W/W)Azone and 10%(W/W) 1,2-propylene glycol.The effect on accumulative release and the content of drug in rat skin were studied by using Franz diffusion cell and rat skin. The results suggested that comparison to gel, liposome gel was increase in accumulative release(or so 1.5 times) and high in the content of drug in rat skin(or so 2 times).The effect on drug release between liposome gel and gel was studied by using Franz diffusion cell and bag filter. The results suggested that the release rate of liposome gel was slower than gel.We studied the content assay and the physicochemical properties of liposome gel. Its content was 2mg·g-1 and pH was 6.49.The results of stability tests indicated that liposome gel stabilize on 25℃and 4℃.The results of pharmacodynamics indicated that comparison to gel, liposome gel stayed a long local anesthetic time and high local anesthetic strength. We studied irritation test of liposome gel that had no irritation to intact skin and damaged skin by rabbit.