Emulsion particle size control method based on high-pressure homogenization process

Abstract

The invention discloses an emulsion particle size control method based on a high-pressure homogenization process, which comprises the following steps: premixing: mixing an oil phase, a water phase and an emulsifier, and carrying out preliminary emulsification to obtain a crude emulsion; primary homogenization: carrying out primary high-pressure homogenization treatment on the crude emulsion under a first pressure condition of 15-25 MPa to obtain a primary emulsion; second-stage homogenization: carrying out second high-pressure homogenization treatment on the first-stage emulsion under a second pressure condition of 50MPa-70MPa to obtain a second-stage emulsion; and third-stage homogenization: carrying out third high-pressure homogenization treatment on the second-stage emulsion under a third pressure condition of 5-15 MPa to obtain the target emulsion. According to the emulsion particle size control method based on the high-pressure homogenization process, through a three-stage pressure cooperation strategy of'low-first high-second low-first ', the excellent control ability on emulsion particle size distribution is achieved, the smaller average particle size can be obtained, and the polydispersity index can be obviously reduced.

Description

Technical Field

[0001] This invention relates to the field of chemical technology, and in particular to a method for controlling the particle size of emulsions based on a high-pressure homogenization process. Background Technology

[0002] In modern chemical, pharmaceutical, food, and cosmetic fields, emulsions, as a dispersion system that uniformly mixes two immiscible solutions (usually oil and water), have extremely wide applications. From oral liquids and injections to high-end skincare products, the physical stability and functional properties of emulsions largely determine the quality, safety, and efficacy of the final product. Many properties of emulsions, such as appearance, stability, bioavailability, and the delivery efficiency of active ingredients, are closely related to the particle size and uniformity of their internal droplets. Generally speaking, the smaller the droplet size and the narrower the distribution range, the higher the physical stability of the emulsion, and the more aesthetically pleasing and delicate the system. At the same time, an increased specific surface area also facilitates the release and absorption of functional ingredients.

[0003] High-pressure homogenization is currently the most mainstream and efficient mechanical method for obtaining micro-sized emulsion droplets in industrial production. Its basic principle is to force a premixed coarse emulsion through an extremely narrow homogenizing slit or a homogenizing valve with a specific structure under extremely high pressure. During this process, the fluid is subjected to enormous shear forces, impact forces, and cavitation effects, thereby breaking the dispersed phase droplets into even finer particles.

[0004] Despite the powerful capabilities of high-pressure homogenization technology, traditional single-stage or simple multi-stage homogenization processes still have significant limitations in precisely controlling particle size distribution. Firstly, many existing processes tend to use a single high pressure for repeated processing to achieve the smallest possible particle size. However, this approach involves overly concentrated and abrupt energy input, easily leading to localized overheating, which can denature or degrade shear-sensitive active ingredients (such as proteins and certain polymer emulsifiers), while also exacerbating equipment wear. More importantly, while high pressure alone can break up most droplets, it is difficult to eliminate the problem of a wide particle size distribution caused by re-agglomeration between droplets or residual large particles that have not been sufficiently broken up. This means that the product may contain both excessively fine droplets and insufficiently broken large droplets simultaneously, and this inhomogeneity poses a threat to the long-term stability of the emulsion.

[0005] Secondly, another type of process may employ constant medium or low pressure for multi-stage processing. While this method is gentler, it has limited ability to break down initial droplets, often failing to overcome particle size limits and thus unable to obtain highly concentrated submicron or nanoscale emulsions, limiting its application in high-end products.

[0006] Furthermore, existing production processes are mostly open-loop systems, lacking real-time monitoring and dynamic adjustment capabilities. Even minute batch-to-batch variations in materials, fluctuations in ambient temperature, or slight changes in equipment condition can lead to variations in the particle size of the final product, affecting batch-to-batch consistency. This unpredictability is unacceptable for fields requiring stringent quality control, such as the pharmaceutical industry.

[0007] Therefore, it is necessary to provide a new method for controlling emulsion particle size based on high-pressure homogenization process to solve the above-mentioned technical problems. Summary of the Invention

[0008] To address the aforementioned technical problems, this invention provides a homogenization process that can balance efficient crushing with fine finishing. It not only produces emulsions with sufficiently small average particle size but also achieves a highly uniform particle size distribution. Furthermore, it possesses good process robustness and a high level of intelligence to cope with various variables in industrial production and stably produce high-quality products.

[0009] This invention provides a method for controlling emulsion particle size based on high-pressure homogenization process, comprising the following steps: S1: Premixing: The oil phase, aqueous phase and emulsifier are mixed and pre-emulsified to obtain a crude emulsion; S2: Primary homogenization: The crude emulsion is subjected to a first high-pressure homogenization treatment under a first pressure condition of 15 MPa to 25 MPa to obtain a primary emulsion. S3: Secondary homogenization: The primary emulsion is subjected to a second high-pressure homogenization treatment under a second pressure condition of 50MPa to 70MPa to obtain a secondary emulsion; S4: Third-stage homogenization: The secondary emulsion is subjected to a third high-pressure homogenization treatment under a third pressure condition of 5 MPa to 15 MPa to obtain the target emulsion.

[0010] Preferably, the first pressure ranges from 17 MPa to 22 MPa, the second pressure ranges from 55 MPa to 65 MPa, and the third pressure ranges from 5 MPa to 12 MPa.

[0011] Preferably, the first pressure is 20 MPa, the second pressure is 60 MPa, and the third pressure is 10 MPa.

[0012] Preferably, in step S2 and / or step S3 and / or step S4, the type of homogenizing valve used in the high-pressure homogenization process is selected from one of the following: slit valve, collision valve, or jet homogenizing valve.

[0013] Preferably, the high-pressure homogenization process in step S2 is repeated 1 to 3 times; and / or, the high-pressure homogenization process in step S3 is repeated 2 to 5 times; and / or, the high-pressure homogenization process in step S4 is repeated 2 to 5 times.

[0014] Preferably, after step S4, the method further includes: S5: Feedback adjustment: Online detection of the average particle size of the target emulsion; The detected average particle size is compared with a predetermined target range, and based on the comparison result, the magnitude of the first pressure and / or the second pressure is dynamically adjusted by ±2 MPa.

[0015] Compared with related technologies, the emulsion particle size control method based on high-pressure homogenization process provided by the present invention has the following beneficial effects: This invention provides an emulsion particle size control method based on high-pressure homogenization. Through a three-stage pressure synergy strategy of "low pressure first, then high pressure, then low pressure again," it achieves excellent control over the emulsion particle size distribution. The first stage of low-pressure treatment gently and effectively breaks down the coarse emulsion, avoiding excessive energy concentration that could lead to emulsifier structural damage or localized overheating. The second stage of high-pressure treatment is the core stage for achieving droplet nano-scale formation. Within a selected high-pressure range, intense shearing, cavitation, and impaction processes efficiently refine the droplets to the target nanoscale. The third stage of low-pressure treatment plays a crucial "polishing" and homogenization role, effectively eliminating any small aggregates or abnormally large particles that may have been generated in the preceding high-pressure stage. This significantly narrows the emulsion particle size distribution, resulting not only in a smaller average particle size but also a significant reduction in the polydispersity index, leading to a better monodispersity and more concentrated distribution in the emulsion system. This fundamentally improves the physical stability of the product and effectively delays phenomena such as stratification, flocculation, and Australtic ripening during storage.

[0016] Secondly, this method not only improves product quality but also reflects process optimization and intelligence. By rationally distributing the total energy input to different process stages, it avoids excessive mechanical shear stress on emulsifiers and active ingredients, helping to protect shear-sensitive substances and enhancing the functionality of the final product. The introduced online detection and feedback adjustment mechanism transforms the entire production process from a static, experience-driven model to a dynamic, data-driven intelligent model. The system can automatically detect minor deviations in product quality and adjust key process parameters in a timely and accurate manner to compensate, greatly enhancing the robustness of the production line and ensuring a high degree of consistency in product quality between different production batches, thus meeting high-standard quality control requirements. Attached Figure Description

[0017] Figure 1 The flowchart of the emulsion particle size control method based on high-pressure homogenization process provided by the present invention is shown. Detailed Implementation

[0018] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0019] Example 1 like Figure 1 As shown in the figure, this embodiment provides a method for controlling emulsion particle size based on high-pressure homogenization process, and the specific steps are as follows: S1: Premix: Weigh 10 parts by weight of oil phase (soybean oil) and 8 parts by weight of emulsifier (Tween-80), and stir evenly in a 60℃ water bath; separately weigh 82 parts by weight of aqueous phase (ionized water), and slowly add the aqueous phase to the oil phase mixture at a stirring speed of 800 rpm, and continue stirring for 30 minutes to carry out preliminary emulsification and obtain crude emulsion.

[0020] S2: Primary homogenization: The crude emulsion is transferred to the feed tank of a high-pressure homogenizer. The first pressure is set to 20 MPa. A slit-type homogenizer valve is selected to circulate the crude emulsion twice under this pressure to obtain the primary emulsion.

[0021] S3: Secondary homogenization: The obtained primary emulsion is placed in the same high-pressure homogenizer, the second pressure is adjusted to 60MPa, and the jet homogenizer valve is replaced. The primary emulsion is circulated 4 times under this pressure condition to obtain the secondary emulsion.

[0022] S4: Three-stage homogenization: The obtained secondary emulsion is introduced into a high-pressure homogenizer, the third pressure is adjusted to 10MPa, and a collision valve is used to circulate the secondary emulsion three times under this pressure condition to obtain the target emulsion.

[0023] The target emulsion, obtained by offline detection using a laser particle size analyzer, had an average particle size of 235 nm and a polydispersity index (PDI) of 0.12.

[0024] Example 2 A method for controlling emulsion particle size based on high-pressure homogenization process, including feedback adjustment, is described below: S1: Premix: Weigh 60 parts by weight of oil phase (medium-chain triglycerides) and 4 parts by weight of emulsifier (soybean lecithin), mix and heat to 70°C to dissolve; separately weigh 5 parts by weight of glycerol, dissolve in 31 parts by weight of water for injection, heat to the same temperature as the aqueous phase, use a high-shear dispersing emulsifier (10000rpm) to pour the aqueous phase into the oil phase, shear for 3 minutes to obtain a crude emulsion.

[0025] S2: Primary homogenization: The crude emulsion is processed by a high-pressure homogenizer, with the first pressure set at 17 MPa. A slit valve is used, and the process is repeated 3 times to obtain the primary emulsion.

[0026] S3: Secondary homogenization: The primary emulsion is further processed by setting the second pressure to 55 MPa, replacing it with a collision valve, and repeating the process 5 times to obtain the secondary emulsion.

[0027] S4: Three-stage homogenization: The secondary emulsion is further processed, and the third pressure is set to 5 MPa. The collision valve is still used, and the process is repeated 4 times to obtain the preliminary target emulsion.

[0028] S5: Feedback Adjustment: An online dynamic light scattering particle size analyzer is integrated at the homogenizer outlet to detect the average particle size of the target emulsion in real time. The predetermined target average particle size range is set to 280±15nm. The first detection yields an average particle size of 310nm, which exceeds the upper limit of the target range. Based on the comparison result, the control system dynamically adjusts the process parameters: the second pressure (originally 55MPa) is increased by +2MPa to 57MPa. Subsequently, the system reprocesses a batch of crude emulsion according to the adjusted parameters (first pressure 17MPa, second pressure 57MPa, third pressure 5MPa), and the online detection is performed again. The resulting emulsion has an average particle size of 285nm, which falls within the target range. The system locks this set of parameters for subsequent production.

[0029] Example 3 This embodiment provides a method for preparing nanoemulsions loaded with active ingredients based on a high-pressure homogenization process. The specific steps are as follows: S1: Premix: Weigh 2 parts by weight of vitamin A palmitate (active ingredient in the oil phase), 28 parts by weight of caprylic / capric triglyceride (carrier in the oil phase) (total 30 parts by weight of oil phase), and 7 parts by weight of polysorbate-80 (emulsifier). Mix them evenly. Weigh 5 parts by weight of 1,3-butanediol and dissolve it in 58 parts by weight of purified water as the aqueous phase. Add the aqueous phase to the oil phase while stirring at 500 rpm. Then homogenize the mixture at 8000 rpm for 2 minutes using a high-speed homogenizer to obtain a crude emulsion.

[0030] S2: Primary homogenization: The crude emulsion is transferred to a high-pressure homogenizer, the first pressure is set to 22 MPa, a jet-type homogenizer valve is selected, and the process is repeated once to obtain the primary emulsion.

[0031] S3: Secondary homogenization: The primary emulsion is further processed by setting a second pressure of 65 MPa and using a jet homogenizing valve. The process is repeated 3 times to obtain the secondary emulsion.

[0032] S4: Three-stage homogenization: The secondary emulsion is further processed, the third pressure is set to 12MPa, the valve is replaced with a slit valve, and the process is repeated twice to obtain the target emulsion.

[0033] The target emulsion was tested and found to have an average particle size of 210 nm, a PDI of 0.18, high encapsulation efficiency, and good stability.

[0034] The three-stage homogenization and feedback control method provided by this invention achieves precise, efficient and stable control of emulsion particle size through stepwise pressure setting and dynamic optimization.

[0035] This invention provides an emulsion particle size control method based on high-pressure homogenization. Through a three-stage pressure synergy strategy of "low pressure first, then high pressure, then low pressure again," it achieves excellent control over the emulsion particle size distribution. The first stage of low-pressure treatment gently and effectively breaks down the coarse emulsion, avoiding excessive energy concentration that could lead to emulsifier structural damage or localized overheating. The second stage of high-pressure treatment is the core stage for achieving droplet nano-scale formation. Within a selected high-pressure range, intense shearing, cavitation, and impaction processes efficiently refine the droplets to the target nanoscale. The third stage of low-pressure treatment plays a crucial "polishing" and homogenization role, effectively eliminating any small aggregates or abnormally large particles that may have been generated in the preceding high-pressure stage. This significantly narrows the emulsion particle size distribution, resulting not only in a smaller average particle size but also a significant reduction in the polydispersity index, leading to a better monodispersity and more concentrated distribution in the emulsion system. This fundamentally improves the physical stability of the product and effectively delays phenomena such as stratification, flocculation, and Australtic ripening during storage.

[0036] Secondly, this method not only improves product quality but also reflects process optimization and intelligence. By rationally distributing the total energy input to different process stages, it avoids excessive mechanical shear stress on emulsifiers and active ingredients, helping to protect shear-sensitive substances and improving the functionality of the final product. More importantly, the introduced online detection and feedback adjustment mechanism transforms the entire production process from a static, experience-driven model to a dynamic, data-driven intelligent model. The system can automatically detect minor deviations in product quality and adjust key process parameters in a timely and accurate manner to compensate, greatly enhancing the robustness of the production line and ensuring a high degree of consistency in product quality between different production batches, thus meeting high-standard quality control requirements.

[0037] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural or procedural transformations made based on the content of the present invention specification and drawings, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. A method for controlling emulsion particle size based on high-pressure homogenization process, characterized in that, Includes the following steps: S1: Premixing: The oil phase, aqueous phase and emulsifier are mixed and pre-emulsified to obtain a crude emulsion; S2: Primary homogenization: The crude emulsion is subjected to a first high-pressure homogenization treatment under a first pressure condition of 15 MPa to 25 MPa to obtain a primary emulsion. S3: Secondary homogenization: The primary emulsion is subjected to a second high-pressure homogenization treatment under a second pressure condition of 50MPa to 70MPa to obtain a secondary emulsion; S4: Third-stage homogenization: The secondary emulsion is subjected to a third high-pressure homogenization treatment under a third pressure condition of 5 MPa to 15 MPa to obtain the target emulsion.

2. The method for controlling emulsion particle size based on high-pressure homogenization process according to claim 1, characterized in that, The first pressure ranges from 17 MPa to 22 MPa, the second pressure ranges from 55 MPa to 65 MPa, and the third pressure ranges from 5 MPa to 12 MPa.

3. The method for controlling emulsion particle size based on high-pressure homogenization process according to claim 2, characterized in that, The first pressure is 20 MPa, the second pressure is 60 MPa, and the third pressure is 10 MPa.

4. The method for controlling emulsion particle size based on high-pressure homogenization process according to claim 1, characterized in that, In step S2 and / or step S3 and / or step S4, the type of homogenizing valve used in the high-pressure homogenization process is selected from one of the following: slit valve, collision valve, or jet homogenizing valve.

5. The method for controlling emulsion particle size based on high-pressure homogenization process according to claim 1, characterized in that, The high-pressure homogenization process in step S2 is repeated 1 to 3 times; and / or, the high-pressure homogenization process in step S3 is repeated 2 to 5 times; and / or, the high-pressure homogenization process in step S4 is repeated 2 to 5 times.

6. The method for controlling emulsion particle size based on high-pressure homogenization process according to claim 1, characterized in that, Following step S4, the following is also included: S5: Feedback adjustment: Online detection of the average particle size of the target emulsion; The detected average particle size is compared with a predetermined target range, and based on the comparison result, the magnitude of the first pressure and / or the second pressure is dynamically adjusted by ±2 MPa.

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