Amorolfine hydrochloride cream and preparation method thereof

Abstract

The invention relates to an amorolfine hydrochloride emulsifiable paste. The amorolfine hydrochloride emulsifiable paste is prepared from the following raw materials in parts by weight: amorolfine hydrochloride, white vaseline, liquid paraffin, carbomer 934P, polyoxyl 40 stearate, stearyl alcohol, phenoxyethanol, edetate disodium, sodium hydroxide and water. The preparation method of the amorolfine hydrochloride emulsifiable paste comprises the following steps: S1, preparing a water phase; S2, preparing an oil phase; and S3, preparing the emulsifiable paste. The invention relates to preparation equipment of amorolfine hydrochloride cream. The preparation equipment comprises a main shell, an outer shell and a partition plate, according to the amorolfine hydrochloride emulsifiable paste and the preparation method thereof, the problem that an existing amorolfine hydrochloride emulsifiable paste preparation method is not prone to industrial large-scale preparation is solved, and the preparation method and preparation equipment are simple in technological process, easy to operate and suitable for industrial large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to an amorolfine hydrochloride cream and a preparation method thereof. Background Art

[0002] The active ingredient of Amorolfine hydrochloride is Amorolfine. The chemical name of Amorolfine is Morpholinerofine, and the chemical name is (±) cis-4-[2-methyl-3-(p-tert-amylphenyl)propyl]-2,6-dimethylmorpholine. It is a topical antifungal drug. Its appearance is white or off-white powder, which is soluble in methanol, glacial acetic acid, ethanol, slightly soluble in acetonitrile, and difficult to dissolve in water.

[0003] Amorolfine hydrochloride is a derivative of morpholine and a new broad-spectrum antifungal drug. It achieves antibacterial and bactericidal effects by interfering with the biosynthesis of ergosterol in the fungal cell membrane. Currently, there are two dosage forms on the market in China: cream and liniment. The specification of amorolfine hydrochloride cream preparation is 0.25%, and it is clinically used to treat dermatophyte diseases caused by dermatophytes; tinea pedis (tinea pedis, athlete's foot), tinea cruris, tinea corporis, and cutaneous candidiasis. According to clinical experimental results, the cure rate of fungal diseases is 80% to 90%.

[0004] The instructions for the French Galderma Amorolfine Hydrochloride Cream state that its auxiliary materials are polyoxyl 40 stearate, liquid paraffin, white vaseline, stearyl alcohol, carbomer, sodium hydroxide, phenoxyethanol, disodium edetate and water. From the above introduction, it can be seen that amorolfine hydrochloride is difficult to dissolve in water, and the raw material drug is also insoluble in the oil phase during the experiment, that is, how to use the emulsifier polyoxyl 40 stearate to prepare a stable state in which the raw material drug exists better than the commercial product; in addition, the CN101485625A patent proposes that the use of polyoxyl 40 stearate as an emulsifier requires high-speed stirring and high-speed homogenization when the oil and water phases are mixed. The order of adding materials to the traditional O / w cream is that the oil phase is added to the water phase, and white vaseline is more sensitive to temperature (melting point is 45-60°C), so how to provide a preparation method that is easy to scale up in industry is still a research hotspot in this field. Summary of the invention

[0005] In view of the shortcomings of the prior art, an amorolfine hydrochloride cream and a preparation method thereof are provided to solve the problem that the current amorolfine hydrochloride cream preparation method is not easy to prepare on an industrial scale. The preparation method and the preparation equipment process are relatively simple, easy to operate, and suitable for industrial scale production.

[0006] The present invention is achieved through the following technical solutions:

[0007] The invention discloses an amorolfine hydrochloride cream, which is composed of the following raw materials in parts by weight: 0.01-1 part of amorolfine hydrochloride, 1-10 parts of white vaseline, 1-15 parts of liquid paraffin, 0.5-10 parts of carbomer 934P, 1-10 parts of polyoxyl 40 stearate, 0.5-15 parts of stearyl alcohol, 0.1-1.0 parts of phenoxyethanol, 0.05-0.2 parts of disodium edetate, 0.1-1.0 parts of sodium hydroxide and an appropriate amount of water.

[0008] A preparation method of amorolfine hydrochloride cream comprises the following steps:

[0009] S1, preparing an aqueous phase, dissolving disodium edetate and phenoxyethanol in parts by weight of the constituent raw materials in water, adding carbomer 934P to swell the dissolved phase, and heating the dissolved phase to 80° C. for standby use to obtain an aqueous phase liquid;

[0010] S2, prepare the oil phase, weigh the weight parts of liquid paraffin, white vaseline, polyoxyl 40 stearate and stearyl alcohol as the raw materials, add them into a container, heat to 80°C to melt, and obtain an oil phase liquid;

[0011] S3, prepare cream, add the aqueous phase liquid obtained in step S1 to the bottom of the container of step S2 under stirring, make the added aqueous phase liquid enter below the oil phase liquid, stir slowly for 20 minutes, then homogenize at high speed for 30 minutes, then add amorolfine hydrochloride raw material drug pre-sieved with 100 mesh sieve under the condition of cooling to 35-55°C; add sodium hydroxide aqueous solution after vacuum stirring for 60 minutes, stir for 20 minutes and then continue to slowly cool to 20-30°C to obtain amorolfine hydrochloride cream.

[0012] A preparation device for amorolfine hydrochloride cream, comprising a main shell, an outer shell and a partition, wherein the main shell is cylindrical, the partition is transversely arranged at the upper inner part of the main shell, and the partition divides the inner space of the main shell into an upper water phase cavity and a lower oil phase cavity, the outer shell is sleeved at intervals on the outer side of the circumference of the lower end of the main shell, and a heating cavity is formed between the outer shell and the main shell, the upper part of the heating cavity is connected to the lower part of the water phase cavity, and the lower part of the heating cavity is connected to the bottom of the oil phase cavity;

[0013] The oil phase chamber and the heating chamber are both provided with heating devices;

[0014] The top of the water phase chamber is provided with a water inlet and a powder inlet, the upper part of the oil phase chamber is provided with a feed pipe, a liquid inlet pipe and an air extraction pipe, the air extraction pipe is provided with a vacuum pump, and the bottom of the oil phase chamber is provided with an emulsion outlet.

[0015] In order to further realize the present invention, the following technical solutions may be preferably selected:

[0016] Preferably, the height position of the upper end of the outer shell is higher than the height position of the partition, the lower part of the water phase chamber passes through the main shell and is connected to the upper part of the heating chamber, and a solenoid valve is provided at the connection between the water phase chamber and the heating chamber.

[0017] Preferably, a liquid adding tube is provided between the heating chamber and the oil phase chamber. The liquid adding tube is longitudinally arranged, the upper end of the heating tube is connected to the bottom surface of the main shell body, and the lower end is fixed to the bottom surface of the outer shell body. An opening is provided at the lower part of the liquid adding tube, and a solenoid valve and a one-way valve are provided at the upper end of the liquid adding tube. The flow direction of the one-way valve is from the heating chamber to the oil phase chamber.

[0018] Preferably, the heating device in the oil phase cavity is arranged at the lower part and bottom surface of the oil phase cavity and is attached to the main shell, and the heating device in the heating cavity is arranged at the bottom of the heating cavity. Temperature sensors are arranged in the oil phase cavity and the heating cavity, and the temperature sensors are connected to the heating device signals.

[0019] Preferably, the liquid inlet pipe includes an integrally formed liquid inlet section and a heat preservation section, the heat preservation section is spirally arranged in the heating chamber, one end of the liquid inlet section is located outside the outer shell, and the other end is connected to the heat preservation section, one end of the heat preservation section away from the liquid inlet section is connected to the oil phase chamber, and the connection point between the heat preservation section and the oil phase chamber is located at the upper edge of the heating device in the oil phase chamber.

[0020] Preferably, the preparation equipment also includes a stirring mechanism, which includes a rotating shaft, which is rotatably arranged on the partition and located at the axis center of the main shell, the upper part of the rotating shaft is located at the lower part of the water phase chamber and a plurality of upper stirring rods are arranged along its radial direction, and the lower part of the rotating shaft is located at the lower part of the oil phase chamber and a plurality of lower stirring rods are arranged.

[0021] Preferably, the lower stirring rods are divided into two groups spaced longitudinally, and the lower stirring rods of the two groups are staggered one by one, the upper ends of the lower stirring rods located at the bottom are hinged to the lower end of the rotating shaft, and the upper ends of the lower stirring rods located at the top are hinged to the upper part of the rotating shaft.

[0022] Preferably, a feeding mechanism is provided in the middle of the rotating shaft, and the feeding mechanism is located on the lower side of the partition. The feeding mechanism includes a feeding rod and a feeding sleeve. The feeding sleeve is annular and rotatably sleeved on the rotating shaft. A closed feeding cavity is formed between the circumferential inner wall of the feeding sleeve and the circumferential outer wall of the rotating shaft. The feeding cavity is connected to the feeding pipe. The middle part of the rotating shaft is a hollow structure. The cavity of the hollow structure forms a material guiding cavity. The material guiding cavity is located in a section of the feeding sleeve and is connected to the feeding cavity. The feeding rod is a hollow rod structure with an outer end inclined downward and a closed end. The inner end of the feeding rod is fixedly connected to the rotating shaft and connected to the lower end of the material guiding cavity. A plurality of microholes are provided on the lower side of the feeding rod along its length.

[0023] Through the above technical solution, the beneficial effects of the present invention are:

[0024] Microscopic observation of the existing amorolfine hydrochloride cream shows that it does not belong to a suspension cream, but there is a small amount of undissolved raw material medicine in the microscopic field of view. The raw material medicine in the present invention is pre-treated by finding a suitable matrix, dissolving the drug in the matrix or dissolving the drug in a small amount of organic solvent, and then mixing with the matrix or grinding the drug into fine powder, first suspending in a suitable solvent, and then adding to the matrix or grinding the drug into fine powder. Adding to the matrix or special drugs should adopt a special adding method, and the specific pretreatment method can be determined according to the dosage composition of the prescription.

[0025] The method for preparing the cream of the present invention is different from that of conventional creams. The oil phase composition of the product contains white vaseline, stearyl alcohol and other oil phase components which are sensitive to temperature. According to conventional preparation methods, the feeding tank or pipeline needs to adopt insulation measures. The present invention adopts the method of adding the water phase to the oil phase, thereby avoiding the above-mentioned problem and adjusting the corresponding process parameters to prepare samples that meet the requirements.

[0026] The conventional cream preparation process includes water phase preparation, oil phase preparation and emulsification. The emulsification process adopts the order of adding oil phase to water phase to form colostrum. A small amount of oil phase at the same temperature is used to rinse the container to complete the material transfer to avoid material loss. Finally, high-speed stirring and / or high-speed homogenization are used to form a cream with uniform emulsion droplets.

[0027] Because the density of the oil phase is lower than that of the water phase, when the oil phase is added to the water phase, the oil phase will float on the upper layer of the water phase, which is conducive to subsequent homogenization. When the water phase is added to the oil phase, the water phase will sink to the lower layer of the oil phase. Its sinking path is uneven, which is not conducive to subsequent homogenization. Therefore, the emulsification process usually adopts the addition order of oil phase to water phase.

[0028] The preparation process of the present invention is different from that of conventional creams except for conventional water phase preparation and oil phase preparation. First, the oil phase composition of the product contains white vaseline, stearyl alcohol and other oil phase components that are sensitive to temperature. The melting point of white vaseline is 45-60°C, the coagulation temperature range of polyoxyl 40 stearate is 39-45°C, and the melting point of stearyl alcohol is 52-55°C. The conventional emulsification feeding sequence is that the oil phase is added to the water phase. If the conventional preparation method is followed, the product needs to separate a portion of the prescribed amount of oil phase or heat water to a suitable temperature to rinse the oil pan. The operation is cumbersome and the material transfer is incomplete due to the solidification of the material due to the low temperature of the initial pipeline. In order to avoid such a situation, insulation measures need to be taken.

[0029] The present invention adopts the method of adding the water phase to the oil phase. It is known that under the same conditions, the same mass of water heats up slowly, while the oil heats up quickly. When the temperature is raised to the same level, water absorbs more heat, and when dissipating heat within the same time, the temperature of the water drops slowly, while the oil is just the opposite. Therefore, the water phase is not easy to solidify compared with the oil phase, and large-scale production is easy to operate, so the above-mentioned problems will not occur. After the colostrum is formed, a cream with uniform emulsion droplets is prepared with the help of high-speed stirring and / or high-speed homogenization, and the corresponding key process parameters are subsequently adjusted to prepare samples that are equivalent to or better than commercial products.

[0030] According to the method for preparing amorolfine hydrochloride cream of the present invention, the sample prepared on the basis of the prescription composition and dosage of the commercial product has the advantages of being better than the commercial product in terms of stability and the microscopic state of the raw material in the cream matrix, and the product has the advantages of fine properties and the droplet particle size being comparable to that of the commercial product.

[0031] The amorolfine hydrochloride cream preparation equipment of the present invention has simple process and operation and is suitable for industrial scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 It is a structural cross-sectional view of the preparation equipment of the present invention;

[0033] Figure 2 It is a structural schematic diagram of the preparation equipment of the present invention;

[0034] Figure 3 For the present invention Figure 1 Sectional view at AA in the middle;

[0035] Figure 4 For the present invention Figure 1 Sectional view at the middle BB;

[0036] Figure 5 For the present invention Figure 1 Enlarged view of point C in the middle;

[0037] Figure 6 It is a schematic diagram of the connection between the liquid inlet pipe and the main housing of the present invention;

[0038] Figure 7 It is a structural schematic diagram of the stirring mechanism of the present invention;

[0039] Figure 8 It is a structural cross-sectional view of the stirring mechanism of the present invention;

[0040] Among them: 1-main shell; 2-outer shell; 3-partition; 4-water phase chamber; 5-oil phase chamber; 6-heating chamber; 7-heating device; 8-feed pipe; 9-liquid inlet pipe; 10-vacuum pipe; 11-liquid adding pipe; 12-rotating shaft; 13-upper stirring rod; 14-lower stirring rod; 15-feed rod; 16-feed sleeve; 901-liquid inlet section; 902-insulation section. DETAILED DESCRIPTION

[0041] In the description of the present invention, it is also necessary to explain that, unless otherwise clearly specified and limited, the terms "set", "install", "connect", and "connect" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0042] The following will be combined with the drawings in the embodiments of the invention to clearly and completely describe the technical solutions in the embodiments of the invention. Obviously, the described embodiments are only part of the embodiments of the invention, not all of the embodiments. Based on the embodiments of the invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the invention.

[0043] Embodiment 1:

[0044] The invention discloses an amorolfine hydrochloride cream, which is composed of the following raw materials in parts by weight: 0.2788 parts of amorolfine hydrochloride, 8 parts of white vaseline, 12 parts of stearyl alcohol, 10 parts of liquid paraffin, 5 parts of polyoxyl 40 stearate, 1.5 parts of carbomer 934P, 1 part of phenoxyethanol, 0.2 parts of disodium edetate, 0.5 parts of sodium hydroxide and an appropriate amount of water.

[0045] A preparation method of amorolfine hydrochloride cream comprises the following steps:

[0046] S1, preparing an aqueous phase, dissolving disodium edetate and phenoxyethanol in parts by weight of the constituent raw materials in water, adding carbomer 934P to swell the dissolved phase, and heating the dissolved phase to 80° C. for standby use to obtain an aqueous phase liquid;

[0047] S2, prepare the oil phase, weigh the weight parts of liquid paraffin, white vaseline, polyoxyl 40 stearate and stearyl alcohol as the raw materials, add them into a container, heat to 80°C to melt, and obtain an oil phase liquid;

[0048] S3, prepare cream, add the aqueous phase liquid obtained in step S1 to the bottom of the container of step S2 under stirring, make the added aqueous phase liquid enter below the oil phase liquid, stir slowly for 20 minutes, then homogenize at high speed for 30 minutes, then add amorolfine hydrochloride raw material drug pre-sieved with 100 mesh sieve under the condition of cooling to 35-55°C; add sodium hydroxide aqueous solution after vacuum stirring for 60 minutes, stir for 20 minutes and then continue to slowly cool to 20-30°C to obtain amorolfine hydrochloride cream.

[0049] Embodiment 2:

[0050] The invention discloses an amorolfine hydrochloride cream, which is composed of the following raw materials in parts by weight: 0.2788 parts of amorolfine hydrochloride, 8 parts of white vaseline, 12 parts of stearyl alcohol, 10 parts of liquid paraffin, 5 parts of polyoxyl 40 stearate, 1.5 parts of carbomer 934P, 1 part of phenoxyethanol, 0.2 parts of disodium edetate, 0.5 parts of sodium hydroxide and an appropriate amount of water.

[0051] During the preparation process: the original pretreated raw material drug is dispersed with phenoxyethanol and then added, and the rest of the process is the same as Example 1.

[0052] Embodiment 3:

[0053] The invention discloses an amorolfine hydrochloride cream, which is composed of the following raw materials in parts by weight: 0.2788 parts of amorolfine hydrochloride, 8 parts of white vaseline, 12 parts of stearyl alcohol, 10 parts of liquid paraffin, 5 parts of polyoxyl 40 stearate, 1.5 parts of carbomer 934P, 1 part of phenoxyethanol, 0.2 parts of disodium edetate, 0.5 parts of sodium hydroxide and an appropriate amount of water.

[0054] During the preparation process: the original pretreated raw material drug is dispersed with part of liquid paraffin and then added, and the rest of the process is the same as Example 1.

[0055] The formula of the amorolfine hydrochloride cream of the above embodiment is summarized in the table below. The test results of the amorolfine hydrochloride cream content, pH value, droplet size, and in vitro release are as follows:

[0056]

[0057] The properties, related substances, content, pH value and particle size of the amorolfine hydrochloride cream prepared according to Example 1 were tested under accelerated conditions (temperature 40±2°C, relative humidity 75%±5%) for 2 months and fast accelerated conditions (temperature 50±2°C, relative humidity 75%±5%) for 30 days. The test results are as follows:

[0058]

[0059]

[0060]

[0061] As can be seen from the above table, the properties, pH value, particle size, content and related properties of the amorolfine hydrochloride cream of Example 1 did not change significantly during the stability period, indicating that the preparation process is stable and can meet the needs of large-scale production.

[0062] Embodiment 4:

[0063] like Figure 1-Figure 8As shown, a preparation device for amorolfine hydrochloride cream comprises a main shell 1, an outer shell 2 and a partition 3, the main shell 1 is cylindrical, the partition 3 is transversely arranged at the upper inner part of the main shell 1, the partition 3 divides the inner space of the main shell 1 into an upper water phase chamber 4 and a lower oil phase chamber 5, the outer shell 2 is sleeved at intervals on the outer side of the lower end of the main shell 1, a heating chamber 6 is formed between the outer shell 2 and the main shell 1, the upper part of the heating chamber 6 is connected to the lower part of the water phase chamber 4, and the lower part of the heating chamber 6 is connected to the bottom of the oil phase chamber 5;

[0064] The oil phase chamber 5 and the heating chamber 6 are both provided with a heating device 7;

[0065] A water inlet and a powder inlet are arranged at the top of the water phase chamber 4, a feed pipe 8, a liquid inlet pipe 9 and an air extraction pipe 10 are arranged at the upper part of the oil phase chamber 5, the air extraction pipe 10 is provided with a vacuum pump, and an emulsion outlet is arranged at the bottom of the oil phase chamber 5.

[0066] The height position of the upper end of the outer shell 2 is higher than the height position of the partition 3. The lower part of the water phase chamber 4 passes through the main shell 1 and is connected to the upper part of the heating chamber 6. A solenoid valve is provided at the connection between the water phase chamber 4 and the heating chamber 6.

[0067] A liquid adding pipe 11 is arranged between the heating chamber 6 and the oil phase chamber 5. The liquid adding pipe 11 is arranged longitudinally. The upper end of the heating pipe is connected to the bottom surface of the main shell 1, and the lower end is fixed to the bottom surface of the outer shell 2. An opening is arranged at the lower part of the liquid adding pipe 11. A solenoid valve and a one-way valve are arranged at the upper end of the liquid adding pipe 11. The flow direction of the one-way valve is from the heating chamber 6 to the oil phase chamber 5.

[0068] In order to facilitate accurate control of the temperature in the oil phase chamber 5 and the heating chamber 6, the heating device 7 in the oil phase chamber 5 is arranged at the lower part and bottom surface of the oil phase chamber 5 and is attached to the main shell 1, and the heating device 7 in the heating chamber 6 is arranged at the bottom of the heating chamber 6. Temperature sensors are provided in the oil phase chamber 5 and the heating chamber 6, and the temperature sensors are connected with the heating device 7 by signal; the heating device 7 in the oil phase chamber 5 heats the materials in the oil phase chamber 5 and the materials in the heating chamber 6 at the same time, and the heating device 7 in the heating chamber 6 heats the materials in the heating chamber 6.

[0069] In order to avoid material adhesion and clogging or adhesion to the tube wall or the inner wall of the main shell 1, the liquid inlet pipe 9 includes an integrally formed liquid inlet section 901 and an insulation section 902. The insulation section 902 is spirally arranged in the heating chamber 6. One end of the liquid inlet section 901 is located on the outside of the outer shell 2, and the other end is connected to the insulation section 902. The end of the insulation section 902 away from the liquid inlet section 901 is connected to the oil phase chamber 5. The connection between the insulation section 902 and the oil phase chamber 5 is located on the upper edge of the heating device 7 in the oil phase chamber 5.

[0070] In order to optimize the product structure, in this embodiment, the preparation equipment also includes a stirring mechanism, which includes a rotating shaft 12, which is rotatably arranged on the partition 3 and located at the axis center of the main shell 1, the upper part of the rotating shaft 12 is located at the lower part of the water phase chamber 4 and is radially provided with a plurality of upper stirring rods 13, and the lower part of the rotating shaft 12 is located at the lower part of the oil phase chamber 5 and is provided with a plurality of lower stirring rods 14; one power source is used to simultaneously stir the water phase chamber 4 and the oil phase chamber 5, which simplifies the equipment and is more conducive to large-scale industrial production.

[0071] In order to ensure uniform shaping and mixing of the cream, the lower stirring rods 14 are divided into two groups spaced apart longitudinally. The lower stirring rods 14 of the two groups are staggered one by one. The upper end of the lower stirring rod 14 located at the bottom is hinged to the lower end of the rotating shaft 12, and the upper end of the lower stirring rod 14 located at the top is hinged to the upper part of the rotating shaft 12.

[0072] In order to further improve the uniformity, a feeding mechanism is provided in the middle of the rotating shaft 12, and the feeding mechanism is located on the lower side of the partition 3. The feeding mechanism includes a feeding rod 15 and a feeding sleeve 16. The feeding sleeve 16 is annular and rotatably sleeved on the rotating shaft 12. A closed feeding chamber is formed between the circumferential inner wall of the feeding sleeve 16 and the circumferential outer wall of the rotating shaft 12, and the feeding chamber is connected to the feeding pipe 8. The middle part of the rotating shaft 12 is a hollow structure, and the cavity of the hollow structure forms a material guiding chamber, which is located in a section of the feeding sleeve 16 and is connected to the feeding chamber. The feeding rod 15 is a hollow rod structure with an outer end inclined downward and a closed end. The inner end of the feeding rod 15 is fixedly connected to the rotating shaft 12 and is connected to the lower end of the material guiding chamber. A plurality of micropores are provided on the lower side of the feeding rod 15 along its length.

[0073] Embodiment 5:

[0074] First, water, disodium edetate and phenoxyethanol are sequentially injected into the water phase chamber 4 through the water inlet, and stirred evenly to dissolve the disodium edetate and phenoxyethanol in the water. Then, carbomer 934P is injected into the water phase chamber 4 through the powder inlet for swelling. After the swelling is completed, the solenoid valve at the connection between the water phase chamber 4 and the heating chamber 6 is opened, and the liquid in the water phase chamber 4 flows into the heating chamber 6. The heating device 7 in the heating chamber 6 heats the liquid therein to 80° C. to obtain a water phase liquid.

[0075] While preparing the aqueous phase liquid, liquid paraffin, white vaseline, polyoxyl 40 stearate and stearyl alcohol are injected into the oil phase cavity 5 through the liquid inlet pipe 9, and the heating device 7 in the oil phase cavity 5 heats the materials therein to 80° C. to melt them and obtain the oil phase liquid; at this time, the temperature in the oil phase cavity 5 is relatively high, the heating device 7 in the oil phase cavity 5 operates at high power, and the heating device 7 in the heating cavity 6 operates at low power, so that the aqueous phase liquid in the heating cavity 6 is maintained at 80° C.; when injecting liquid paraffin, white vaseline, polyoxyl 40 stearate and stearyl alcohol, the vacuum pump can be started to generate suction in the oil phase cavity 5, so as to facilitate the materials to enter the oil phase cavity 5 and avoid blockage.

[0076] First start the vacuum pump, and then open the solenoid valve at the upper end of the liquid adding pipe 11. At this time, the feed pipe 8 and the liquid inlet pipe 9 are both in a closed state. The vacuum pump extracts the air in the oil phase chamber 5 and at the same time extracts the water phase liquid in the heating chamber 6 into the oil phase chamber 5. When the water phase liquid entering the oil phase chamber 5 reaches a predetermined amount, the solenoid valve and the vacuum pump are closed in turn.

[0077] First, stir slowly. At this time, the rotation speed of the shaft 12 is relatively low, and the lower stirring rod 14 is maintained at the lowest state, stirring the liquid in the oil phase chamber 5 to the maximum extent to ensure the mixing effect. Then, homogenize at high speed. At this time, the rotation speed of the shaft 12 is high, and the lower stirring rod 14 is turned upward by the centrifugal force to ensure the homogenization effect.

[0078] The power of the heating device 7 in the oil phase chamber 5 is reduced to reduce the temperature in the oil phase chamber 5 to 35-55° C., and then the vacuum pump is started and the feed pipe 8 is in an open state and the liquid feed pipe 9 is in a closed state. The amorolfine hydrochloride bulk drug pre-screened with a 100-mesh sieve enters the feed rod 15 through the feed chamber and the guide chamber, and is evenly sprinkled into the oil phase chamber 5 while the feed rod 15 rotates. Then the feed pipe 8 is in a closed state. At this time, the oil phase chamber 5 is in a closed state. The vacuum pump continues to work until the oil phase chamber 5 is in a vacuum state, and the stirring is continued. After stirring for a period of time, the liquid inlet pipe 9 is opened, and the sodium hydroxide aqueous solution enters the oil phase chamber 5 through the liquid inlet pipe 9. After continuing to stir for a period of time, the power of the heating device 7 in the oil phase chamber 5 is further reduced to reduce the temperature in the oil phase chamber 5 to 20-30°C, and amorolfine hydrochloride cream is obtained; when the power of the heating device 7 in the oil phase chamber 5 is reduced, its heat conduction to the aqueous phase liquid in the heating chamber 6 is reduced. In order to maintain the aqueous phase liquid in the heating chamber 6 at 80°C, the power of the heating device 7 in the heating chamber 6 should be increased accordingly.

[0079] Finally, it should be noted that the above are only preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An amorolfine hydrochloride cream, characterized in that: The amorolfine hydrochloride cream is composed of the following raw materials in parts by weight: 0.01-1 part of amorolfine hydrochloride, 1-10 parts of white vaseline, 1-15 parts of liquid paraffin, 0.5-10 parts of carbomer 934P, 1-10 parts of polyoxyl 40 stearate, 0.5-15 parts of stearyl alcohol, 0.1-1.0 parts of phenoxyethanol, 0.05-0.2 parts of disodium edetate, 0.1-1.0 parts of sodium hydroxide, and an appropriate amount of water.

2. A method for preparing amorolfine hydrochloride cream, characterized in that: The following steps are involved: S1, preparing an aqueous phase, dissolving disodium edetate and phenoxyethanol in parts by weight of the constituent raw materials in water, adding carbomer 934P to swell the dissolved phase, and heating the dissolved phase to 80° C. for standby use to obtain an aqueous phase liquid; S2, prepare the oil phase, weigh the weight parts of liquid paraffin, white vaseline, polyoxyl 40 stearate and stearyl alcohol as the raw materials, add them into a container, heat to 80°C to melt, and obtain an oil phase liquid; S3, prepare cream, add the aqueous phase liquid obtained in step S1 to the bottom of the container of step S2 under stirring, make the added aqueous phase liquid enter below the oil phase liquid, stir slowly for 20 minutes, then homogenize at high speed for 30 minutes, then add amorolfine hydrochloride raw material drug pre-sieved with 100 mesh sieve under the condition of cooling to 35-55°C; add sodium hydroxide aqueous solution after vacuum stirring for 60 minutes, stir for 20 minutes and then continue to slowly cool to 20-30°C to obtain amorolfine hydrochloride cream.

3. A preparation device for amorolfine hydrochloride cream, the preparation device is based on the preparation method of amorolfine hydrochloride cream according to claim 2, characterized in that: The preparation device comprises a main shell (1), an outer shell (2) and a partition (3); the main shell (1) is cylindrical; the partition (3) is transversely arranged at the upper inner portion of the main shell (1); the partition (3) divides the inner space of the main shell (1) into an upper water phase chamber (4) and a lower oil phase chamber (5); the outer shell (2) is sleeved on the outer circumference of the lower end of the main shell (1); a heating chamber (6) is formed between the outer shell (2) and the main shell (1); the upper portion of the heating chamber (6) is connected to the lower portion of the water phase chamber (4); and the lower portion of the heating chamber (6) is connected to the bottom of the oil phase chamber (5); The oil phase chamber (5) and the heating chamber (6) are both provided with a heating device (7); The top of the water phase chamber (4) is provided with a water inlet and a powder inlet, the upper part of the oil phase chamber (5) is provided with a feed pipe (8), a liquid inlet pipe (9) and an air extraction pipe (10), the air extraction pipe (10) is provided with a vacuum pump, and the bottom of the oil phase chamber (5) is provided with an emulsion outlet.

4. A preparation device for amorolfine hydrochloride cream according to claim 3, characterized in that, The height position of the upper end of the outer shell (2) is higher than the height position of the partition (3); the lower part of the water phase chamber (4) passes through the main shell (1) and is connected to the upper part of the heating chamber (6); and a solenoid valve is provided at the connection point between the water phase chamber (4) and the heating chamber (6).

5. A preparation device for amorolfine hydrochloride cream according to claim 3, characterized in that, A liquid adding pipe (11) is provided between the heating chamber (6) and the oil phase chamber (5). The liquid adding pipe (11) is arranged longitudinally, the upper end of the heating pipe is connected to the bottom surface of the main shell (1), and the lower end is fixed to the bottom surface of the outer shell (2). An opening is provided at the lower part of the liquid adding pipe (11), and a solenoid valve and a one-way valve are provided at the upper end of the liquid adding pipe (11). The flow direction of the one-way valve is from the heating chamber (6) to the oil phase chamber (5).

6. A preparation device for amorolfine hydrochloride cream according to claim 3, characterized in that, The heating device (7) in the oil phase chamber (5) is arranged at the lower part and bottom surface of the oil phase chamber (5) and is attached to the main housing (1); the heating device (7) in the heating chamber (6) is arranged at the bottom of the heating chamber (6); temperature sensors are arranged in both the oil phase chamber (5) and the heating chamber (6); and the temperature sensors are connected to the heating device (7) by signals.

7. A preparation device for amorolfine hydrochloride cream according to claim 6, characterized in that, The liquid inlet pipe (9) comprises an integrally formed liquid inlet section (901) and a heat-insulating section (902); the heat-insulating section (902) is spirally arranged in the heating chamber (6); one end of the liquid inlet section (901) is located outside the outer shell (2) and the other end is connected to the heat-insulating section (902); one end of the heat-insulating section (902) away from the liquid inlet section (901) is connected to the oil phase chamber (5); and the connection point between the heat-insulating section (902) and the oil phase chamber (5) is located at the upper edge of the heating device (7) in the oil phase chamber (5).

8. A preparation device for amorolfine hydrochloride cream according to claim 3, characterized in that, The preparation device further comprises a stirring mechanism, the stirring mechanism comprising a rotating shaft (12), the rotating shaft (12) being rotatably disposed on the partition (3) and located at the axis of the main shell (1), the upper portion of the rotating shaft (12) being located at the lower portion of the water phase chamber (4) and having a plurality of upper stirring rods (13) disposed along its radial direction, and the lower portion of the rotating shaft (12) being located at the lower portion of the oil phase chamber (5) and having a plurality of lower stirring rods (14) disposed thereon.

9. A preparation device for amorolfine hydrochloride cream according to claim 8, characterized in that, The lower stirring rods (14) are divided into two groups spaced apart longitudinally. The lower stirring rods (14) of the two groups are arranged alternately one by one. The upper ends of the lower stirring rods (14) located at the lower end are hinged to the lower end of the rotating shaft (12), and the upper ends of the lower stirring rods (14) located at the upper end are hinged to the upper part of the rotating shaft (12).

10. The preparation equipment of amorolfine hydrochloride cream according to claim 8, characterized in that: A feeding mechanism is provided in the middle of the rotating shaft (12), and the feeding mechanism is located on the lower side of the partition (3). The feeding mechanism comprises a feeding rod (15) and a feeding sleeve (16). The feeding sleeve (16) is annular and is rotatably sleeved on the rotating shaft (12). A closed feeding cavity is formed between the circumferential inner wall of the feeding sleeve (16) and the circumferential outer wall of the rotating shaft (12). The feeding cavity is connected to the feeding pipe (8). The middle of the rotating shaft (12) is a hollow structure. The cavity of the hollow structure forms a guide cavity. The guide cavity is located in a section of the feeding sleeve (16) and is connected to the feeding cavity. The feeding rod (15) is a hollow rod structure with an outer end inclined downward and a closed end. The inner end of the feeding rod (15) is fixedly connected to the rotating shaft (12) and is connected to the lower end of the guide cavity. A plurality of micropores are provided on the lower side of the feeding rod (15) along its length.

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