[0024] The present invention will be further described below in conjunction with the drawings and specific embodiments.
[0025] figure 1 This is the schematic diagram of the injection microemulsion preparation system.
[0026] Such as figure 1 As shown, the flurbiprofen axetil injection microemulsion preparation system includes: oil phase tank, water phase tank, mixing pump, high pressure homogenizer, 1# turnover tank, 2# turnover tank, 3# turnover tank and liquid storage tank.
[0027] The oil phase tank has a built-in stator rotor dispersion stirring device, and a jacketed container outside, which plays the role of two-phase mixing and homogenization. The water phase tank has a built-in stirring device and a jacketed container for uniform mixing. The high-pressure homogenizer makes the material in the suspension state flow through the cavity with special internal structure at high speed under the action of ultra-high pressure, and finally achieves the homogenization effect. 1# turnover tank, 2# turnover tank, and 3# turnover tank are all jacketed containers, which act as temporary storage for liquid turnover. The liquid storage tank has a built-in stirring and a jacketed container for cooling and storage.
[0028] The outlets of the oil phase tank and the water phase tank are connected with the inlet of the mixing pump. The outlet of the mixing pump is connected to the inlet of the high-pressure homogenizer. The high-pressure homogenizer has a first homogenization outlet X1 and a homogenization second outlet X2. The homogeneous first outlet X1 is connected with the inlet of the 1# turnover tank, and the outlet of the 1# turnover tank is connected with the inlet of the oil phase tank and/or the water phase tank. The homogeneous second outlet X2 is connected with the inlet of 2# turnover tank; the outlet of 2# turnover tank is connected with the inlet of 3# turnover tank. The 3# turnover tank has a turnover first outlet Y1 and a turnover second outlet Y2. The first outlet Y1 of the turnover is connected with the inlet of the high-pressure homogenizer. The turnover second outlet Y2 is connected with the inlet of the liquid storage tank.
[0029] Homogeneous first outlet X1 has a homogeneous first valve FX1; Homogeneous second outlet X2 has a homogeneous second valve FX2; Turnover first outlet Y1 has a turnover first valve FY1; Turnover second outlet Y2 has a Turnover the second valve FY2. The first homogenization valve FX1 is opened, the second homogenization valve FX2 is closed, and the material in the high-pressure homogenizer is pressed into the 1# turnover tank. The first homogenization valve FX1 is closed, the second homogenization valve FX2 is opened, and the material in the high-pressure homogenizer is pressed into the 2# turnover tank. The first turnover valve FY1 is opened, the second turnover valve FY2 is closed, and the material in the 3# turnover tank is pressed into the high-pressure homogenizer. The first turnover valve FY1 is closed, the second turnover valve FY2 is opened, and the material in the 3# turnover tank is pressed into the liquid storage tank.
[0030] Preheat the oil phase tank and/or water phase tank to 70±5°C. 1# turnover tank, 2# turnover tank, 3# turnover tank are kept at 55±5℃. 3# A filter membrane is set between the turnover tank and the liquid storage tank. The liquid storage tank is cooled while stirring, and the materials are temporarily stored at 22±2℃.
[0031] Preparation method of flurbiprofen axetil injection microemulsion:
[0032] Step A: The oil phase materials enter the oil phase tank for mixing and homogenization, while the water phase materials enter the water phase tank for mixing and homogenization.
[0033] Weigh the main drug flurbiprofen and the auxiliary egg yolk lecithin according to the prescription, add them to the oil phase tank, mix well, and preheat to 70±5℃. Then weigh the soybean oil according to the prescription and add it to the oil phase tank. The oil phase tank is continuously protected by nitrogen, and a stator-rotor emulsifier is used for high-speed shearing.
[0034] Weigh the water for injection WFI according to the prescription and add it to the water phase tank, and then weigh the auxiliary materials according to the prescription: citric acid, glycerin and anhydrous disodium hydrogen phosphate, add them to the water phase tank, stir to dissolve, and then add WFI for injection to the full amount , Preheat to 70±5℃, mix well. Continuous nitrogen protection in the water phase tank.
[0035] Step B: Disperse and homogenize the oil phase tank material and dissolve and mix the water phase tank material through a mixing pump into a high-pressure homogenizer for emulsification and homogenization.
[0036] Step C. The materials in the high-pressure homogenizer are pressed into the 1# turnover tank for heat preservation; the 1# turnover tank is insulated at 55±5℃, and the 1# turnover tank is continuously supplied with nitrogen for protection. The materials in the 1# turnover tank are then pressed into the oil phase tank and/or the water phase tank for mixing, and then pressed into the high pressure homogenizer for emulsification.
[0037] Step C circulates twice to achieve the purpose of dispersing, stirring and homogenizing the materials; then enter step D.
[0038] Step D. The materials in the high-pressure homogenizer are pressed into the 2# turnover tank for heat preservation; at this time, the 2# turnover tank is kept at 55±5℃, and the 2# turnover tank is continuously protected by nitrogen. Then, the material in the 2# turnover tank is pressed into the 3# turnover tank for heat preservation, and the 3# turnover tank is also insulated at 55±5℃, and the 3# turnover tank is continuously supplied with nitrogen for protection. When the 3# turnover tank reaches full volume, the material is pumped into the high-pressure homogenizer by the pump, and then pressed into the high-pressure homogenizer for emulsification and homogenization.
[0039] Step D is cycled three times to achieve the purpose of homogenizing and emulsifying the material. Then go to step E.
[0040] Step E. The material in the high-pressure homogenizer is pressed into the 2# turnover tank for heat preservation; the material in the 2# turnover tank is then pressed into the 3# turnover tank for heat preservation; the material from the 3# turnover tank is filtered through a 1μm filter membrane and enters the liquid storage Tank, the materials in the tank are cooled while stirring, and temporarily stored at 22±2℃.
[0041] The injection microemulsion preparation method in this embodiment is for flurbiprofen axetil injection. The liquid microemulsion preparation method of the present invention can be applied to other injection microemulsion processes, where the cycles of step C and step D can be Adjust according to actual situation.
[0042] Although the content of the present invention has been described in detail through the above preferred embodiments, it should be recognized that the above description should not be considered as limiting the present invention.
