High Pressure Homogenizers

High-Pressure Homogenizers (HPHs) are used for the homogenization of compounds requiring high pressure. These equipment are applicable in the biotechnology, pharmaceutical, food, cosmetic, chemical, and environmental industries, where it is essential to reach particle sizes in a nano range.

High Pressure Homogenizers

Overview

High-pressure homogenizers prepare nanomaterial by producing high flow velocity through a small orifice, using an internal fixed geometry under ultra-high pressure (up to 60,000 psi). During the homogenization process, changes in physical, chemical, and structural properties occur, and as a result, the homogeneous suspension takes place at the nanoscale. A conventional homogenizer has a pressure of up to 15,000 psi, a high-pressure homogenizer can achieve 30,000 psi, and an ultra-high-pressure homogenizer can reach up to 60,000 psi.

High-pressure homogenizers can obtain high-concentrated FLG suspensions with low defect concentrations.

The global high-pressure homogenizers market is growing annually, concurrently raising the nanotechnology market. High-pressure homogenizers, such as nanogenizers, are used to prepare pharmaceutical nanoemulsions. Their pressure exceeds 20,000 psi and features high-quality diamond interaction chambers to achieve a uniform, pharmaceutical-grade nanoparticle size distribution.

The major players in the high-pressure homogenizers market are Krones AG, Genizer LLC, GEA Group, SPX Corporation, Sonic Corporation, Avestin Inc., Bertoli s.r.l, FBF Italia s.r.l, Netzsch Group (Erich NETZSCH GmbH & Co. Holding KG), PHD Technology International LLC, Microfluidics International Corporation, Ekato Holding GmbH, Alitec, Simes SA, Goma Engineering Pvt. Ltd., Milkotek-Hommak, BOS Homogenizers B.V., Silverson Machines Inc., and Frymakoruma GmbH.

Key Principles

The critical component of a high-pressure homogenizer includes a homogenization unit such as a diamond interaction chamber, and a high-pressure pump unit. There is a fixed geometry inside the diamond interaction chamber. Strokes of the piston in the high-pressure pump unit drive the samples through the interaction chamber at supersonic speed. In the chamber, materials are simultaneously subjected to mechanical forces such as high shearing, high-frequency oscillation, cavitation, convective impact, and corresponding thermal effects. These mechanical and physiochemical effects induce changes in the materials' physical, chemical, and particle structure. This results in uniform and smaller nanoparticle size, achieving a homogenization effect.

The interaction chamber is the core of the high-pressure homogenizer, and its geometric internal structure is the main factor determining the effectiveness of the homogenization process. The intensifier pump exerts the required pressure for materials to pass through the interaction chamber at high speed. The pressure's strength and stability ensure the production of high-quality nanomaterials.

Genizer is the leading supplier of high-pressure homogenizers worldwide equipped with microfluidic diamond interaction chambers.

Applications

The high-pressure homogenizers are used extensively in the pharmaceutical, biotechnology, chemical, energy, cosmetic/cosmeceutical, and food/nutraceutical industries in the application of nanoemulsions, nano-dispersions, vaccine adjuvants, lipid nanoparticles, food homogenization, fine chemicals, dairy products, cell disruption, nanoencapsulation, liposomes, deagglomeration, and particle size reduction.

The high-pressure homogenizer utilizes top-down nanotechnology to prepare nanomaterials. The homogenizer and its interaction chamber have several applications in producing nanomaterial and nanotechnology. These applications include:

• Preparation of fat emulsion, microemulsions, liposomes, nanosuspensions, and nanoparticles in the pharmaceutical industry. The high-pressure homogenizer (HPH) in the pharmaceutical industry is used explicitly for size reduction, mixing, and stabilization of dispersions or droplets. In HPH, the liquid is passed through a narrow gap under high pressure, where the different processing parameters lead to changes in globule/particle size.
• Cell disruption, microcapsules, and vaccine adjuvants in biotechnology products;
• Homogenization and emulsification in the food and beverage industry to improve stability, taste, appearance, and encapsulation of nutrients in food products;
• Homogeneous dispersion of products in the cosmetics, fine chemical, and other industries to improve product functionality, increase value, and ensure process stability;
• Dispersion and exfoliation of conductive paste, resistance paste, graphene, carbon nanotubes, and nano-oxides.

Classification

1. By Energy Source

Electric

Electric homogenizers are powered by an electric motor. This category of the homogenizer is further subdivided into two types: direct-drive and intensifier.

Direct-Drive Type

The motor drives the crankshaft to move the plunger back and forth, directly pressurizing the material. Multiple plungers in the crankshaft work together to produce constant pressure and a high flow rate; large quantities of materials are required to produce the constant pressure. To drive the crankshaft, the motor requires a multi-stage gear reduction mechanism, which makes the equipment large in size. The homogenizer with a crankshaft is suitable for large-scale production with low-pressure applications.

Intensifier Type

The motor drives the intensifier to pressurize the material through the interaction chamber in the high-pressure homogenizers. The intensifier system can provide higher pressure, thereby improving the performance of the homogenization process. The flow rate of the homogenizer with an intensifier is lower than it is for the homogenizer with a crankshaft, smaller amounts of materials are required, and the pressure is higher.

It can be used for laboratory applications with small amounts of samples and production applications with high pressure. When equipped with the diamond interaction chamber, the electric high-pressure homogenizer with an intensifier is categorized as a high-end homogenizer. This type is widely used in biology, pharmaceutical, and nanotechnology laboratories. The traditional intensifier is hydraulic, and the new electric cylinder by linear actuator emerges with more performance.

Hand Driven

Hand-driven homogenizers pressurize the material with manual power. The flow rate of a hand homogenizer is low, but it is portable and easy to assemble and disassemble. It requires tiny amounts of materials, making it suitable for small-scale experiments. This type of device is capable of supporting biopharmaceutical laboratories' research and development needs. The manual high-pressure homogenizer is also called the Handgenizer.

Air Driven

The air-driven homogenizer converts the pressure of compressed gas into hydraulic pressure. Therefore, it needs the support of a nitrogen cylinder or an air compressor. This homogenizer's gas consumption and noise levels are high, and its maximum homogenization pressure is generally low. However, since there is no separate intensifier pump structure, its volume is small and suitable for sites equipped with compressed nitrogen.

2. By Principle and Structure of The Interaction Chamber

First Generation: Impact Type

Cavitation Nozzles:

The primary function of this nozzle is cavitation, which leads to the separation of the emulsion and thereby increases the particle size. Under the pressure of the homogenizer, the materials flow into the cavitation nozzle with a tiny aperture at several times the speed of sound. Meanwhile, intense friction and collision occur between the particles and the metal valve parts. This friction reduces the service life of the equipment, and the collisions cause metallic particles to fall into the final products.

Impact Valve:

The impact valve and impact ring structure moderately reduce local wear and prolong the homogenization chamber's service life using tungsten alloy materials. The role of the impact valve is a combination of impact and cavitation. However, its basic principle is the collision of the material in the suspension with the structure of a high-hardness metal (such as tungsten alloy). Therefore, the impact valve still cannot solve the problem of metallic particle residue. Most high-pressure homogenizers have added impact valve components by the first decade of the 20th century.

Second Generation: Interaction Type

Y-Type Interaction Chamber:

The Y-type interaction chamber is a powerful homogenization chamber. In these systems, the flow stream is split into two channels redirected over the same plane at right angles and propelled into a single flow stream. High pressure promotes a high speed at the crossover of the two flows, which results in high shear, turbulence, and cavitation over the single outbound flow stream.

With the unique Y-type structure, the high-pressure solution's high-speed moving materials collide in a process that significantly improves the service life of the chamber over those with more conventional designs. The use of diamond material prevents the formation of metal particle residue.

The Y-type interaction chamber is widely used in preparing pharmaceutical emulsions because it minimizes cavitation and produces exquisite, stable particle size and PDI (poly dispersity index) control ability. Currently, the Y-type diamond interaction chamber is mainly used in high-end nanotechnology, occupying more than 90% of the US pharmaceutical industry. Genizer and Microfluidics Corp. are the leading manufacturers of the diamond interaction chamber. Genizer's temperature-controlled interaction chamber avoids temperature surges and enables working pressure up to 60,000 psi.

Low emulsification efficiency and metallic particle residue are problems caused by homogenization chambers designed with the impact principle. When particles collide with internal metal components during the production of pharmaceutical injections, residual inert metallic particles generate. These metallic particles may gather and form larger particles. In pharmaceutical applications, this is a problem because large particles will decrease capillary blood flow, which in turn will cause mechanical damage to tissues in the human body, causing acute or chronic inflammation. The interaction chamber solves the problems of particle residue and demulsification. However, the chamber's internal structure means that when the products' concentration and viscosity are high, the chamber is more prone to cause flow blocking than impact homogenizers are.

3. By The Principle of Pressurization

The ultra-high-pressure homogenizer needs a significant thrust to push the piston in the cylinder to achieve high-pressure levels. The rotating motor needs to reduce the speed, increase the torque, and convert the linear motion to obtain the linear reciprocating motion with high thrust. The principle of pressurization operates differently in direct-drive type and intensifier-type homogenizers.

Direct-Drive Type

The motor drives the crankshaft to move the plunger back and forth and pressurize the material. Multiple sets of plungers provide constant pressure, and the flow rate is high for this type of homogenizer. However, the minimum material requirements are also high, as is the amount of residual produced.

The crankshaft driven by the motor needs a multi-stage gear reduction mechanism, which limits these homogenizers to moderate efficiency and requires large unit dimensions. This homogenizer type is suitable for the food and chemical industries and other applications that do not have high-pressure requirements.

Intensifier Type

The intensifier-type homogenizer is the result of the development of ultra-high-pressure technology in recent years. One of its mechanisms involves the motor driving the oil pump to pressurize the material through the hydraulic system. The pressure provided by the hydraulic system is higher than in direct-drive homogenizers, while the volume and the minimum material requirement are smaller. The intensifier-type homogenizer can be applied to laboratory and production homogenizers with high pressure.

Hydraulic homogenizers are expensive, but the hydraulic intensifier can achieve low-frequency and high-thrust piston movement, which increases the machine's service life and reduces its maintenance costs. Using parallel four-cylinder technology, stable pressure can be obtained without an accumulator, achieving ultra-high pressure of up to 45,000 psi. In the past, most high-pressure homogenizers were the direct-drive type, but this type's disadvantage is obvious. Its service life is short, and its wearing parts need frequent maintenance, especially those pressure-bearing parts when the pressure is above 100 MPa. Hydraulic homogenizers have a high manufacturing cost but offer a long service life and lower maintenance costs for wearing parts.

Selection

1. Selecting a High-Pressure Generator

Overall, a cylinder with an intensifier is superior to a direct-drive one. Under the same flow rate, higher pressure produces lower frequency, fewer pressure fluctuations, better product quality, and greater equipment durability. At 30,000 psi, a laboratory high-pressure homogenizer can reach less than 10 Hz fluctuation levels instead of 60 Hz from a normal homogenizer.

High-pressure piston materials can be divided into ceramics, tungsten carbide, and hardened stainless steel, with ceramics as the costliest option and hardened stainless steel as the most affordable. Quality and durability align with a cost: Ceramic materials offer the highest quality, followed by hard tungsten alloy, with hardened stainless steel as a lower-quality option.

2. Selecting Homogenization Parts

As a core component of homogenizers, homogenization chambers play a decisive role in achieving optimum results for the process. Different inner constructions of homogenization chambers lead to different results and applications. When selecting a suitable homogenizer, the purchaser must consider both performance and cost. In general, the cost of the first-generation homogenization chamber is more economical, but its performance in the homogenization process is not as good as the second generation's. The second-generation homogenization chamber produces a superior product, but when processing materials with high concentration and viscosity, it is more likely to block than first-generation machines, and its cost is also higher. The interaction chamber with a cooling system, developed by Genizer, can be used for thermally unstable biological and pharmaceutical products.

3. Maximum Homogenizing Pressure

In general, higher homogenizing pressure leads to better quality. This is because the particle size will be much smaller and more uniform if the homogenizer's pressure is higher, which means processors produce the nanomaterial more efficiently. Higher homogenizing pressure also allows more kinds of samples to be processed. For example, emulsions usually require a homogenizing pressure of 20,000 psi to achieve a particle size of 100 nm, while suspensions typically require at least 45,000 psi to reach the nanoscale. It should also be noted that high temperatures will affect the results of the homogenization process. The higher the pressure is, the higher the temperature will be. Because of this, 30,000 psi is the maximum pressure for high-pressure homogenization without a cooling system. Due to the high temperature, the homogenization effect of more than 30,000 psi does not increase with pressure. The development of the ultra-high pressure diamond interaction chamber with a cooling system can effectively reduce the content of large particles and solve the problem of emulsion stability caused by high temperatures. Therefore, machines equipped with this type of chamber can achieve pressures up to 60,000 psi.

4. Product Uniformity

Generating a uniform particle size distribution is essential during the production process. A wide particle size distribution from nanometer to micron is not acceptable, especially if particles larger than 5 um are present in a pharmaceutical emulsion. USP (US Pharmacopeia) regulates the particle size distribution of pharmaceutical emulsions. Interaction chambers produce a more uniform particle size distribution than impact valve homogenizers.

The Future of High-Pressure Homogenizers

In 2010, the FDA announced a recall of eleven batches of clevidipine butyrate injection emulsion across the United States due to the possibility that the emulsion contained inert metallic particles. Particles gathering and forming larger particles would theoretically clog blood capillaries, causing mechanical damage to the body or other acute or chronic inflammations.

Therefore, using the impact type of homogenization chamber in the pharmaceutical industry is not recommended. These models are no longer suitable for mass production of pharmaceutical emulsion injection. The interaction mechanism is also more durable in ultra-high-pressure machines with temperature control. With the increasing demand for nanomaterials, which require higher pressure and higher performance in nano-dispersion, interaction chambers will be more widely used in nanotechnology fields, such as pharmaceuticals, semiconductors, and microelectronics.

In the past century, the homogenizer has experienced many changes, from the shift from low pressure (10,000 psi) to high (20,000 psi) and ultra-high pressure (60,000 psi), from the homogenizing valve design to the use of interaction chambers and chambers with temperature control; from the direct-drive type to the intensifier and multi-pump constant pressure types.

With the development of the high-thrust linear actuator system, high-thrust and low-speed linear motors will be applied in ultra-high-pressure homogenizers. As the pressure increases, temperature control will be a significant technical challenge—and therefore, a temperature-controlled and ultra-high pressure-durable interaction chamber is a major avenue for future development.