Method for preparing ethyl cellulose aqueous dispersion by one-pot method based on ultrasonic treatment

Abstract

The invention provides a method for preparing an ethyl cellulose aqueous dispersion through a one-pot method based on ultrasonic treatment, and belongs to the technical field of ethyl cellulose aqueous dispersion preparation. The method comprises the following steps: mixing and dissolving ethyl cellulose and a solvent under an ultrasonic condition to obtain an ethyl cellulose solution; the preparation method comprises the following steps: under an ultrasonic condition, sequentially adding a plasticizer, oleic acid, ammonia water, a defoaming agent and a suspending aid into an ethyl cellulose solution, uniformly mixing, and then adding water to obtain an oil-in-water type crude emulsion; under an ultrasonic condition, carrying out reduced pressure distillation on the oil-in-water type crude emulsion, and adjusting the solid content and the pH value to obtain a semi-finished product; and carrying out ultrasonic treatment on the semi-finished product to obtain the ethyl cellulose aqueous dispersion. By utilizing the method disclosed by the invention, the problems that the production efficiency is low in the existing ethyl cellulose aqueous dispersion preparation process, and the prepared ethyl cellulose aqueous dispersion is poor in stability and poor in particle uniformity can be solved; the method has the characteristics of high efficiency, simplicity, convenience and low energy consumption, and has popularization and application values.

Description

Technical Field

[0001] This invention belongs to the field of ethyl cellulose aqueous dispersion preparation technology, specifically relating to a one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment. Background Technology

[0002] Ethyl cellulose aqueous dispersions are complex systems formed by dispersing tiny ethyl cellulose (EC) particles in water, with particle sizes typically ranging from 50 to 500 nm. This dispersion possesses numerous excellent properties: it can form mechanically sound films, exhibits good biocompatibility and thermal stability, and remains insoluble in the acidic environment of the human stomach. Based on these properties, ethyl cellulose aqueous dispersions are widely used in the field of pharmaceutical excipients and are included in the Chinese Pharmacopoeia, commonly used as coating materials for sustained-release and controlled-release formulations. Compared to organic solvent coating materials, ethyl cellulose aqueous dispersions, using water as the dispersion medium, offer advantages such as better safety, no environmental pollution, high liquid-to-solid content, low viscosity, ease of handling, and short coating time, and have become one of the important raw materials for drug coating.

[0003] Based on whether volatile solvents are used to dissolve EC during the preparation of ethyl cellulose aqueous dispersions, preparation methods can be divided into solvent-based and solvent-free methods. Traditional solvent-free methods typically require high-temperature screw compounding and plasticizing of ethyl cellulose, resulting in high energy consumption and the risk of oxidative discoloration. Solvent-based methods generally include steps such as dissolution, emulsification, solvent removal, and homogenization. While these methods avoid potential oxidation and discoloration at high temperatures, the presence of surfactants during solvent removal easily generates numerous bubbles, leading to low production efficiency. Furthermore, viscous materials require transport and transfer between multiple devices, resulting in high equipment investment costs, low production efficiency, and difficult equipment cleaning. In addition, particle size is a crucial indicator affecting the storage and application of ethyl cellulose aqueous dispersions. Generally, smaller particle sizes result in higher storage stability and better film uniformity. To ensure product quality, particle size D50 ≤ 300 nm is typically required. Traditional processes often employ energy-intensive high-shear or high-pressure homogenization methods to reduce product particle size.

[0004] To promote the rapid development of the ethyl cellulose and pharmaceutical excipients industry, it is of great significance to develop a method for preparing ethyl cellulose aqueous dispersions that is efficient, simple, low-energy, and easy to industrialize. Summary of the Invention

[0005] The problem this invention aims to solve is to provide a one-pot method for preparing ethyl cellulose aqueous dispersions based on ultrasonic treatment, thereby addressing the issues of low production efficiency and poor stability and particle uniformity in existing ethyl cellulose aqueous dispersion preparation processes.

[0006] The technical solution adopted to solve the technical problem is to provide a one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment, including the following steps: (1) Under ultrasonic conditions, ethyl cellulose is mixed and dissolved with a solvent to obtain an ethyl cellulose solution; (2) Under ultrasonic conditions, plasticizer, oleic acid, ammonia, defoamer and suspending agent are added to the ethyl cellulose solution in sequence and mixed well. Then water is added to obtain an oil-in-water crude emulsion. (3) Under ultrasonic conditions, the oil-in-water crude emulsion was subjected to vacuum distillation, and the solid content and pH value were adjusted to obtain a semi-finished product; (4) The semi-finished product is subjected to ultrasonic treatment to obtain ethyl cellulose aqueous dispersion.

[0007] The beneficial effects of the above-mentioned technical solution in this invention are as follows: Ultrasonic waves are characterized by mild conditions, low energy consumption, and ease of use. They exhibit significant cavitation effects and mechanical vibrations. During the preparation of the crude emulsion, the ultrasonic waves propagate through the liquid, generating alternating high-pressure and low-pressure regions. In the low-pressure region, tiny cavitation bubbles form. When these bubbles rapidly collapse, they release enormous energy, generating strong shear forces, microjets, and turbulence. This breaks down the interfacial tension of the liquid, breaking the dispersed phase into micron- or even nano-sized particles, which are then uniformly dispersed in the continuous phase. As the amount of water added increases, the system undergoes a phase reversal, ultimately forming a stable oil-in-water crude emulsion. Further, during the vacuum distillation of the crude emulsion, the enormous collapse energy released by the cavitation effect directly tears apart the interfacial film formed by the surfactant, breaking the stable structure of the bubbles and causing them to collapse rapidly. Simultaneously, the high-frequency mechanical vibrations of the ultrasonic waves drive the violent movement of liquid molecules within the system, reducing local viscosity and accelerating the rise of bubbles from the liquid phase, preventing bubble retention. This ensures rapid solvent removal from the resulting semi-finished product, avoiding material loss and ensuring the stability of the final ethyl cellulose aqueous dispersion.

[0008] Preferably, in step (1), the ethoxy content of ethyl cellulose is 44-51%, and the viscosity is 3-110 mPa·s; the solvent is at least one of dichloromethane, trichloromethane, and ethyl acetate; the mass ratio of solvent to ethyl cellulose is 2-5:1; the mixing and dissolving temperature is 20-35℃; the ultrasonic frequency is 20-100 kHz, and the power density is 10-300 W / cm². 2 .

[0009] More preferably, in step (1), the ethoxy content of ethyl cellulose is 48-51%, the viscosity is 7-55 mPa·s; the mass ratio of solvent to ethyl cellulose is 3-4:1; the mixing and dissolving temperature is 25-35℃; the ultrasonic frequency is 40-80 kHz, and the power density is 10-200 W / cm².2 .

[0010] More preferably, in step (1), the ethoxy content of ethyl cellulose is 48.3%, the viscosity is 10 mPa·s; the mass ratio of solvent to ethyl cellulose is 4:1; the mixing and dissolving temperature is 25°C; the ultrasonic frequency is 60 kHz, and the power density is 30 W / cm². 2 .

[0011] More preferably, the viscosity of ethyl cellulose is the capillary viscosity of a 5 wt% ethyl cellulose solution measured at 25°C; the solvent of the 5 wt% ethyl cellulose solution is a mixed solvent of ethanol and toluene in a mass ratio of 1:4.

[0012] Preferably, in step (2), the plasticizer is at least one of medium-chain triglycerides, dibutyl sebacate, diethyl phthalate, and dibutyl phthalate; the mass concentration of ammonia is 10-28%; the defoamer is at least one of organosilicon, polyether, and polyether-modified polysiloxane defoamers; and the suspending agent is fumed silica and / or magnesium aluminum silicate.

[0013] More preferably, the mass concentration of ammonia water is 28%.

[0014] More preferably, the defoamer is at least one of polyoxyethylene polyoxypropylene stearate glycerol ether, polyoxyethylene polyoxypropylene glycerol ether, dimethyl silicone oil, polyoxypropylene glycerol ether, diaminopropyl polydimethylsiloxane, and α-[3-[1,3,3,3-tetramethyl-1-(trimethylsilyl-oxo)disiloxane]-propyl-ω-hydroxypolyoxyethylene].

[0015] More preferably, the mass ratio of ethyl cellulose, plasticizer, oleic acid, ammonia, suspending agent and water is 1:0.1~0.25:0.05~0.15:0.1~0.4:0.01~0.08:2.7~5.2; and the mass ratio of defoamer to oil-in-water crude emulsion is 0.05~1:100.

[0016] More preferably, the mass ratio of ethyl cellulose, plasticizer, oleic acid, ammonia, suspending agent and water is 1:0.1~0.2:0.08~0.15:0.15~0.3:0.02~0.06:3.2~4.1; and the mass ratio of defoamer to oil-in-water crude emulsion is 0.3~0.6:100.

[0017] More preferably, the mass ratio of ethyl cellulose, plasticizer, oleic acid, ammonia, suspending agent and water is 1:0.12:0.12:0.18:0.03:3.5; and the mass ratio of defoamer to oil-in-water crude emulsion is 0.11:100.

[0018] Preferably, in step (2), the frequency of the ultrasonic wave is 20~80 kHz and the power density is 10~50 W / cm². 2 The ultrasound time is 3 to 20 minutes.

[0019] More preferably, in step (2), the frequency of the ultrasound is 20~40 kHz and the power density is 10~30 W / cm². 2 The ultrasound time is 8-15 minutes.

[0020] More preferably, in step (2), the frequency of the ultrasound is 30 kHz and the power density is 20 W / cm². 2 The ultrasound time was 10 minutes.

[0021] Preferably, in step (3), the frequency of the ultrasonic wave is 50~100 kHz and the power density is 5~30 W / cm². 2 The vacuum distillation temperature is 20~50℃, and the gauge pressure is -0.090~-0.099 MPa.

[0022] More preferably, in step (3), the frequency of the ultrasound is 60~80 kHz and the power density is 5~15 W / cm². 2 The vacuum distillation temperature is 30~40℃, and the gauge pressure is -0.095~-0.099 MPa.

[0023] More preferably, in step (3), the frequency of the ultrasound is 60 kHz and the power density is 10 W / cm². 2 The vacuum distillation temperature is 35℃ and the gauge pressure is -0.097 MPa.

[0024] Preferably, in step (3), the solid content and pH value are adjusted by adding water and ammonia.

[0025] More preferably, in step (3), the solid content is adjusted to 24.6-24.9% and the pH value is 10.5-10.7.

[0026] Preferably, in step (4), the frequency of the ultrasonic wave is 20~80 kHz and the power density is 50~300 W / cm². 2 The ultrasonic treatment is performed at a temperature of 20-50℃ for 3-30 minutes.

[0027] More preferably, in step (4), the frequency of the ultrasonic wave is 20~40 kHz and the power density is 80~200 W / cm². 2 The ultrasonic treatment is performed at a temperature of 30-45℃ for 5-10 minutes.

[0028] More preferably, in step (4), the frequency of the ultrasound is 30 kHz and the power density is 100 W / cm². 2 The ultrasonic treatment was performed at a temperature of 35°C for 8 minutes.

[0029] The present invention has the following beneficial effects: (1) In the one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment of the present invention, all steps can be completed in one reactor. The viscous material does not need to be transported and transferred between multiple devices, which can greatly improve production efficiency and reduce the difficulty of equipment cleaning. Moreover, the device used does not require a traditional mechanical stirring structure, which can significantly reduce the cost of equipment and improve the sealing performance of the reactor. It has the characteristics of high efficiency, simplicity, low energy consumption and easy industrial production.

[0030] (2) In the one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment of the present invention, the use of ultrasound in the preparation of crude emulsion helps to improve the preparation efficiency, control the particle size of the product, obtain a more uniform crude emulsion, and reduce the difficulty of subsequent ultrasonic homogenization; secondly, the use of the cavitation effect of ultrasound to assist in descaling during the desolvation process can accelerate the elimination of bubbles under depressurization conditions, greatly improve the desolvation efficiency, and prevent bubbles from carrying materials into the pipeline; finally, the use of high energy density ultrasound for homogenization treatment can achieve the same effect as high pressure homogenization treatment, which is far superior to high shear equipment, with low energy consumption and higher efficiency.

[0031] (3) The ethyl cellulose aqueous dispersion prepared by the method of the present invention has a narrow and uniform particle size distribution, D50≤300nm, and the product does not show obvious stratification after being stored at room temperature for 6 months, which meets the requirements of the relevant indicators for ethyl cellulose aqueous dispersion (type B) in the Chinese Pharmacopoeia. Attached Figure Description

[0032] Figure 1 This is a photograph of the ethyl cellulose aqueous dispersion prepared in Example 1; Figure 2 This is a particle size distribution diagram of the ethyl cellulose aqueous dispersion obtained in Example 1; Figure 3 The particle size distribution diagram of the ethyl cellulose aqueous dispersion prepared in Comparative Example 1 is shown. Figure 4 This is a particle size distribution diagram of the ethyl cellulose aqueous dispersion prepared in Comparative Example 4. Figure 5 This is a particle size distribution diagram of the ethyl cellulose aqueous dispersion prepared in Comparative Example 5. Figure 6 The particle size distribution diagram is shown for the ethyl cellulose aqueous dispersion prepared in Comparative Example 6. Detailed Implementation

[0033] The principles and features of the present invention are described below with reference to embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise specified in the embodiments, conventional conditions or conditions recommended by the manufacturer should be followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0034] Example 1 A method for preparing ethyl cellulose aqueous dispersion in a one-pot process based on ultrasonic treatment includes the following steps: (1) Take 100 g of ethyl cellulose with an ethoxy content of 48.3% and a viscosity of 10 mPa·s, and heat it at 25℃, a frequency of 60kHz and a power density of 30 W / cm². 2 Ethyl cellulose was mixed and dissolved in 400 g of dichloromethane under ultrasonic conditions to obtain a transparent ethyl cellulose solution. (2) At a frequency of 30 kHz and a power density of 20 W / cm 2 Under ultrasonic conditions, 12 g of medium-chain triglycerides, 12 g of oleic acid, 18 g of ammonia water with a mass concentration of 28%, 1 g of diaminopropyl polydimethylsiloxane and 3 g of fumed silica were added sequentially to an ethyl cellulose solution and mixed well. Then, 350 g of deionized water was added and the mixture was continuously ultrasonicated for 10 min to obtain an oil-in-water crude emulsion. (3) At a frequency of 60 kHz and a power density of 10 W / cm² 2 Under ultrasonic conditions and a temperature of 35°C, the oil-in-water crude emulsion was subjected to vacuum distillation at a gauge pressure of -0.097 MPa until no solvent was distilled off. Then, 3 g of deionized water and 5 g of ammonia solution with a mass concentration of 28% were added and mixed to obtain a semi-finished product. (4) The semi-finished product was subjected to a temperature of 35℃, a frequency of 30 kHz, and a power density of 100 W / cm². 2 After ultrasonic treatment for 8 minutes, an aqueous dispersion of ethyl cellulose was obtained.

[0035] The actual product of the ethyl cellulose aqueous dispersion prepared in this embodiment is shown in the figure. Figure 1 Particle size distribution is shown in Figure 2 .from Figures 1-2 As can be seen from the above, the ethyl cellulose aqueous dispersion prepared in this embodiment is a milky white suspension with a relatively uniform particle size distribution, a D50 of 177 nm, a D90 of 370 nm, and no obvious stratification after natural storage for 6 months.

[0036] Example 2 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment, differing from Example 1 only in that step (2) is: at a frequency of 30 kHz and a power density of 40 W / cm². 2Under ultrasonic conditions, 12 g of medium-chain triglycerides, 12 g of oleic acid, 18 g of ammonia water with a mass concentration of 28%, 1 g of diaminopropyl polydimethylsiloxane, and 3 g of fumed silica were added sequentially to an ethyl cellulose solution and mixed thoroughly. Then, 350 g of deionized water was added and the mixture was continuously ultrasonicated for 10 min to obtain an oil-in-water crude emulsion. The remaining parameters and steps were the same as in Example 1.

[0037] Example 3 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment, differing from Example 1 only in that step (2) is: at a frequency of 30 kHz and a power density of 20 W / cm². 2 Under ultrasonic conditions, 12 g of medium-chain triglycerides, 12 g of oleic acid, 18 g of ammonia water with a mass concentration of 28%, 1 g of diaminopropyl polydimethylsiloxane, and 3 g of fumed silica were added sequentially to an ethyl cellulose solution and mixed thoroughly. Then, 350 g of deionized water was added and the mixture was continuously ultrasonicated for 3 min to obtain an oil-in-water crude emulsion. The remaining parameters and steps were the same as in Example 1.

[0038] Example 4 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment, differing from Example 1 only in that step (3) is: at a frequency of 80 kHz and a power density of 10 W / cm². 2 Under ultrasonic conditions and a temperature of 35°C, the oil-in-water crude emulsion was subjected to vacuum distillation at a gauge pressure of -0.097 MPa until no solvent was distilled off. Then, 3 g of deionized water and 5 g of ammonia solution with a mass concentration of 28% were added and mixed to obtain a semi-finished product. The remaining parameters and steps were the same as in Example 1.

[0039] Example 5 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment, differing from Example 1 only in that step (3) is: at a frequency of 60 kHz and a power density of 25 W / cm². 2 Under ultrasonic conditions and a temperature of 35°C, the oil-in-water crude emulsion was subjected to vacuum distillation at a gauge pressure of -0.097 MPa until no solvent was distilled off. Then, 3 g of deionized water and 5 g of ammonia solution with a mass concentration of 28% were added and mixed to obtain a semi-finished product. The remaining parameters and steps were the same as in Example 1.

[0040] Example 6 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment differs from Example 1 only in that step (4) involves subjecting the semi-finished product to ultrasonic treatment at a temperature of 35°C, a frequency of 30 kHz, and a power density of 100 W / cm³. 2The ethyl cellulose aqueous dispersion was obtained by ultrasonic treatment for 5 min; the remaining parameters and steps were the same as in Example 1.

[0041] Example 7 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment differs from Example 1 only in that step (4) involves subjecting the semi-finished product to ultrasonic treatment at a temperature of 35°C, a frequency of 30 kHz, and a power density of 200 W / cm³. 2 The ethyl cellulose aqueous dispersion was obtained by ultrasonic treatment for 8 min; the remaining parameters and steps were the same as in Example 1.

[0042] Comparative Example 1 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment, differing from Example 1 only in that step (2) is: at a frequency of 30 kHz and a power density of 5 W / cm². 2 Under ultrasonic conditions, 12 g of medium-chain triglycerides, 12 g of oleic acid, 18 g of ammonia water with a mass concentration of 28%, 1 g of diaminopropyl polydimethylsiloxane, and 3 g of fumed silica were added sequentially to an ethyl cellulose solution and mixed thoroughly. Then, 350 g of deionized water was added and the mixture was continuously ultrasonicated for 10 min to obtain an oil-in-water crude emulsion. The remaining parameters and steps were the same as in Example 1.

[0043] The particle size distribution of the ethyl cellulose aqueous dispersion prepared in this comparative example is as follows: Figure 3 As shown. From Figure 3 As can be seen from the data, the particle size D50 of the ethyl cellulose aqueous dispersion prepared in this comparative example is 244 nm, which is lower than 300 nm, but from the data... Figure 3 It can be seen that there are still many particles with a diameter of several micrometers. This is because the ultrasonic power density is too low to provide enough energy for the formation of the coarse emulsion, resulting in insufficient uniformity of the coarse emulsion, and therefore large particles appear in the final product.

[0044] Comparative Example 2 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment, differing from Example 1 only in that step (3) is: at a frequency of 30 kHz and a power density of 10 W / cm². 2 Under ultrasonic conditions and a temperature of 35°C, the oil-in-water crude emulsion was subjected to vacuum distillation at a gauge pressure of -0.097 MPa until no solvent was distilled off. Then, 3 g of deionized water and 5 g of ammonia solution with a mass concentration of 28% were added and mixed to obtain a semi-finished product. The remaining parameters and steps were the same as in Example 1.

[0045] Observations during vacuum distillation revealed that a large number of bubbles were generated during the desolventizing process, and these bubbles were difficult to eliminate quickly on their own. The bubbles carried the material rapidly into the vacuum pipeline, resulting in significant material loss. This was because the ultrasonic frequency was too low, producing larger cavitation bubbles that released stronger energy upon collapse. While defoaming, this also caused the solvent to evaporate, generating even more bubbles. Consequently, the bubbles could not be eliminated in time, making it impossible to stably prepare the product.

[0046] Comparative Example 3 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment, differing from Example 1 only in that step (3) is: at a frequency of 60 kHz and a power density of 3 W / cm². 2 Under ultrasonic conditions and a temperature of 35°C, the oil-in-water crude emulsion was subjected to vacuum distillation at a gauge pressure of -0.097 MPa until no solvent was distilled off. Then, 3 g of deionized water and 5 g of ammonia solution with a mass concentration of 28% were added and mixed to obtain a semi-finished product. The remaining parameters and steps were the same as in Example 1.

[0047] During vacuum distillation, it was observed that the desolvation time using this method was as long as 145 min, which was much longer than the 36 min in Example 1, resulting in low production efficiency. This was because the energy input by the ultrasound was too low, resulting in a limited cavitation effect, thus the defoaming effect was insufficient and the desolvation time was too long.

[0048] Comparative Example 4 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment differs from Example 1 only in that step (4) involves subjecting the semi-finished product to ultrasonic treatment at a temperature of 35°C, a frequency of 30 kHz, and a power density of 350 W / cm³. 2 The ethyl cellulose aqueous dispersion was obtained by ultrasonic treatment for 8 min; the remaining parameters and steps were the same as in Example 1.

[0049] The particle size distribution of the ethyl cellulose aqueous dispersion prepared in this comparative example is as follows: Figure 4 As shown. From Figure 4 As can be seen from the results, the ethyl cellulose aqueous dispersion prepared in this comparative example has an uneven particle size distribution, with a D50 exceeding 300 nm. It separates into layers after 6 months of storage, indicating poor stability. This is because the ultrasonic power density is too high, causing partial demulsification of the product, resulting in particle agglomeration and the formation of large particles of tens of micrometers. After 6 months of storage, the sedimentation of these large particles leads to the separation of the system.

[0050] Comparative Example 5 A one-pot method for preparing ethyl cellulose aqueous dispersion based on ultrasonic treatment differs from Example 1 only in that step (4) involves subjecting the semi-finished product to ultrasonic treatment at a temperature of 35°C, a frequency of 100 kHz, and a power density of 100 W / cm³. 2The ethyl cellulose aqueous dispersion was obtained by ultrasonic treatment for 8 minutes; the remaining parameters and steps were the same as in Example 1.

[0051] The particle size distribution of the ethyl cellulose aqueous dispersion prepared in this comparative example is as follows: Figure 5 As shown. From Figure 5 As can be seen, the ethyl cellulose aqueous dispersion prepared in this comparative example has an uneven particle size distribution, with large particles of several micrometers present. This is because the ultrasonic frequency is too high, providing more dispersed and gentler energy, thus resulting in insufficient homogenization and the presence of larger particles.

[0052] Comparative Example 6 A method for preparing ethyl cellulose aqueous dispersion in a one-pot process based on ultrasonic treatment is different from Example 1 only in that step (4) is omitted, and the semi-finished product obtained in step (3) is the ethyl cellulose aqueous dispersion; the remaining parameters and steps are the same as in Example 1.

[0053] The particle size distribution of the ethyl cellulose aqueous dispersion prepared in this comparative example is as follows: Figure 6 As shown. From Figure 6 As can be seen, the ethyl cellulose aqueous dispersion prepared in this comparative example has an uneven particle size distribution, with large particles of several micrometers present. This is because the volatilization of ammonia during the desolventizing process reduces the content of the emulsifier ammonium oleate in the system, thereby reducing the emulsification effect and causing some particles to agglomerate, resulting in a large number of large particles.

[0054] Test case The properties of the ethyl cellulose aqueous dispersions prepared in Examples 1-7 and Comparative Examples 1-6 were tested according to the Chinese Pharmacopoeia (2025 edition), and the results are shown in Table 1.

[0055] Table 1. Performance test results of ethyl cellulose aqueous dispersion

[0056] As can be seen from Table 1, the physicochemical properties of the ethyl cellulose aqueous dispersion prepared by the method of the present invention meet the requirements of the Chinese Pharmacopoeia. The average particle size is ≤300 nm, the storage stability is good, and there is no obvious stratification after 6 months of natural storage. Moreover, the desolvation time is short, which is conducive to improving production efficiency. In contrast, the production efficiency of the comparative method is poor, the ethyl cellulose aqueous dispersion particles are unevenly dispersed, and it is very easy to settle or stratify, resulting in poor storage effect.

[0057] The present invention has been described according to the above embodiments. It should be understood that the above embodiments do not limit the present invention in any way. All technical solutions obtained by equivalent substitution or equivalent transformation fall within the scope of the present invention.

Claims

1. A method for the one-pot preparation of an ethyl cellulose aqueous dispersion based on ultrasonic treatment, characterized in that, The method comprises the following steps: (1) dissolving ethyl cellulose and solvent under ultrasonic condition to obtain ethyl cellulose solution; (2) adding plasticizer, oleic acid, ammonia, defoaming agent and suspending agent into the ethyl cellulose solution under ultrasonic condition, mixing, and then adding water to obtain oil-in-water coarse emulsion; (3) performing vacuum distillation on the oil-in-water coarse emulsion under ultrasonic condition, and adjusting solid content and pH value to obtain semi-finished product; (4) performing ultrasonic treatment on the semi-finished product to obtain ethyl cellulose water dispersion.

2. The process for the one-pot preparation of an ethyl cellulose aqueous dispersion based on ultrasonic treatment according to claim 1, characterized in that, The ethoxyl content of the ethyl cellulose in step (1) is 44-51%, and the viscosity is 3-110 mPa·s; the solvent is at least one of dichloromethane, trichloromethane and ethyl acetate; the mass ratio of the solvent to ethyl cellulose is 2-5:1; the temperature of the mixing and dissolving is 20-35℃; the frequency of the ultrasonic wave is 20-100 kHz, and the power density is 10-300 W / cm 2 .

3. The one-pot process for the production of an ethyl cellulose aqueous dispersion based on ultrasonic treatment according to claim 1, characterized in that, The plasticizer in step (2) is at least one of medium-chain triglyceride, dibutyl sebacate, diethyl phthalate and dibutyl phthalate; the mass concentration of the ammonia is 10-28%; the defoaming agent is at least one of silicone, polyether and polyether-modified polysiloxane defoaming agent; and the suspending agent is fumed silica and / or magnesium aluminum silicate.

4. The one-pot process for the production of an ethyl cellulose aqueous dispersion based on ultrasonic treatment according to claim 3, characterized in that, The defoaming agent is at least one of polyoxyethylene polyoxypropylene stearate glycerol ether, polyoxyethylene polyoxypropylene glycerol ether, dimethyl silicone oil, polyoxypropylene glycerol ether, bisaminopropyl polydimethylsiloxane and alpha-[3-[1,3,3,3-tetramethyl-1-(trimethylsilyl-oxo)disiloxane]-propyl-omega-hydroxypolyoxyethylene).

5. The one-pot process for the preparation of an ethyl cellulose aqueous dispersion based on ultrasonic treatment according to any one of claims 1 to 4, characterized in that, The mass ratio of the ethyl cellulose, plasticizer, oleic acid, ammonia, suspending agent and water is 1:0.1-0.25:0.05-0.15:0.1-0.4:0.01-0.08:2.7-5.2; and the mass ratio of the defoaming agent to the oil-in-water coarse emulsion is 0.05-1:

100.

6. The one-pot ultrasonic treatment based process for preparing an ethyl cellulose aqueous dispersion according to claim 1, characterized in that, The frequency of the ultrasonic wave in the step (2) is 20-80 kHz, the power density is 10-50 W / cm 2 , and the ultrasonic time is 3-20 min.

7. The one-pot ultrasonic wave treatment based process for the preparation of an ethyl cellulose aqueous dispersion according to claim 1, characterized in that, The frequency of the ultrasonic wave in the step (3) is 50-100 kHz, and the power density is 5-30 W / cm 2 ; the reduced pressure distillation temperature is 20-50℃, and the pressure is -0.090--0.099 MPa.

8. The one-pot ultrasonic treatment based process for preparing an ethyl cellulose aqueous dispersion according to claim 1, characterized in that, The adjustment of the solid content and pH value in step (3) is performed by adding water and ammonia. The method comprises the following steps: (1) dissolving ethyl cellulose and solvent under ultrasonic condition to obtain ethyl cellulose solution; (2) adding plasticizer, oleic acid, ammonia, defoaming agent and suspending agent into the ethyl cellulose solution under ultrasonic condition, mixing, and then adding water to obtain oil-in-water coarse emulsion; (3) performing vacuum distillation on the oil-in-water coarse emulsion under ultrasonic condition, and adjusting solid content and pH value to obtain semi-finished product; (4) performing ultrasonic treatment on the semi-finished product to obtain ethyl cellulose water dispersion. The plasticizer in step (2) is at least one of medium-chain triglyceride, dibutyl sebacate, diethyl phthalate and dibutyl phthalate; the mass concentration of the ammonia is 10-28%; the defoaming agent is at least one of silicone, polyether and polyether-modified polysiloxane defoaming agent; and the suspending agent is fumed silica and / or magnesium aluminum silicate. The defoaming agent is at least one of polyoxyethylene polyoxypropylene stearate glycerol ether, polyoxyethylene polyoxypropylene glycerol ether, dimethyl silicone oil, polyoxypropylene glycerol ether, bisaminopropyl polydimethylsiloxane and alpha-[3-[1,3,3,3-tetramethyl-1-(trimethylsilyl-oxo)disiloxane]-propyl-omega-hydroxypolyoxyethylene). The mass ratio of the ethyl cellulose, plasticizer, oleic acid, ammonia, suspending agent and water is 1:0.1-0.25:0.05-0.15:0.1-0.4:0.01-0.08:2.7-5.2; and the mass ratio of the defoaming agent to the oil-in-water coarse emulsion is 0.05-1:

100. The adjustment of the solid content and pH value in step (3) is performed by adding water and ammonia.

9. The one-pot ultrasonic treatment based process for the preparation of an ethyl cellulose aqueous dispersion according to claim 1, characterized in that, The frequency of the ultrasonic wave in the step (4) is 20-80 kHz, and the power density is 50-300 W / cm 2 ; the temperature of the ultrasonic treatment is 20-50℃, and the time is 3-30 min.

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