| Liquid crystal is a novel drug delivery system for local anesthetic,which is firstly applied in cosmetics for the last few years. Tetracaine liquid crystal,used as a model in our study,is prepared and evaluated in vitro to provide a rapid action and a reduction of ache for preoperative surface anesthesia. Various purity lecithin is used as surfactant while isopropyl myristate is employed as oil phase and anhydrous alcohol as co surfactant. The influence of purity of lecithin and the ratio of lecithin to anhydrous alcohol (Km) on the formation of liquid crystal is studied.Tetracaine is a long action local anesthetic and its anesthetic potency is 16 times as high as procaine. It is accepted as effective surface anesthetics. An ultra-violet spectrophotography (UV) method is developed to determine the concentration of tetracaine in liquid crystal. The UV detective wavelength of tetracaine is 310nm and under this condition the interference of blank accessories can be avoided. The mean recovery in the concentration range of 5 to 50(ag/ml is 100.11 + 1.21%,while the precision of determination within day and between day respectively is 1.81+0.23% and 2.02 + 0.05%. A high performance liquid chromatography (HPLC) method is established to determine the permeation effect of tetracaine liquid crystal through skin in vitro. The chosen detective UV wavelength is 3 lOnm and there is no interference of blank permeation liquid through skin. The conditions are as follows,Waters HPLC instrument:Sanrui SR2000 workstation,510 HPLC pump,Waters 2487 UV detector. Mobile phase:methanol-water- triethylamine (75:25:0.04),flow rate l.Oml/min. Detective wavelength 310nm. Sensitivity 0.01AUFS. The mean recovery in the concentration range of 20 to 100jag/ml is 100.23 + 1.99%,and the precision of determination within day and between day is 1.96 + 0.05% and 1.78 + 0.09% respectively. The mean recovery in the concentration range of 100 to 700g/ml is 100.87+1.54%,and the precision of determination within day and between day respectively is 0.53 + 0.09% and 1.67 + 0.67%.The permeation of tetracaine liquid crystal through exercised mouse skin in the presence of lecithin,oil phase,Km and water phase is performed with modified Franz-diffusion cells. With the orthogonal design and according to the various permeation velocity the best formula is chosen to go ahead. The viscosity,stability,toxicity,stimulation and skin allergic reaction tests are made using this best formula and the controlled anesthetic pharmacodynamic test is holden using rabbit cornea reflection method with EMLA cream as contrast.Pseudo-ternary phase diagrams have been constructed for lecithin of various purity and various ratio of lecithin to alcohol (Km). It is showed that the liquid crystal formation region is wider when high purity lecithin is used than low purity lecithin used. At the same time,the change of the liquid crystal formation brought by the alteration of Km also shows that it needs a lot of surfactant during the process of liquid crystal formulation.The best formula is chosen according to the various permeation velocity with the orthogonal design. The stability of tetracaine liquid crystal is tested respectively at 40c and 60c. It shows that this formulation is stable at room centigrade but may have inversion easily at higher centigrade. The results of toxicity,stimulation and skin allergic reaction tests show that tetracaine liquid crystal has good stability and no toxicity or allergic reaction. It is a safe surface anesthetic.The rabbit cornea reflection method is used in controlled anesthetic pharmacodynamic test of tetracaine liquid crystal with EMLA cream as contrast. The results show tetracaine liquid crystal has no significant difference on anesthesia effect with EMLA cream.
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