High Pressure Homogenizer – Principle, Types, Parts, Uses

What is Homogenizer?

• In today’s context, homogenizers are utilised to produce more consistent emulsions/suspension in a high efficiency process.
• A broad variety of homogenizers have been created to run at varied pressures and capacities depending on the product mixture.
• In addition to product enhancements, today’s homogenizers also feature reduced noise and vibration and reduced maintenance.
• Homogenization is the process of emulsifying two immiscible liquids (i.e. liquids that are not soluble in one another) or uniformly spreading solid particles throughout a liquid. Homogenization is a unit operation using a kind of processing equipment called to homogenizers that are oriented at lowering the size of droplets in liquid-liquid or solid liquid dispersions.
• The benefits include increased product stability, homogeneity, consistency, viscosity, shelf life, improved flavour and colour.
• It has become a standard industrial technique in food and beverage, chemical, pharmaceutical and personal care industries.
• The method of homogenization was created and patented by Auguste Gaulin in 1899 when he outlined a process for homogenising milk.
• Gaulin’s invention, a three-piston thruster furnished with small filtering tubes, was presented at the World Fair in Paris in 1900. Since then, his name has become synonymous with homogenization.
• High-pressure homogenizers have been employed to disrupt microbial cells for many years. The approach has been proven to be usually suitable for a variety of bacteria, yeast and mycelia.
• This sort of homogenizer works by driving cell suspensions through a very thin channel or aperture under pressure. Subsequently, and depending on the type of high- pressure homogenizer, they may or may not impinge at high velocity on a hard-impact ring or on another high-velocity stream of cells coming from the opposite direction. Machines which contain the impingement design are more effective than those which do not. Disruption of the cell wall happens by a combination of the huge pressure drop, highly focused turbulent eddies, and intense shearing pressures.

• The rate of cell rupture is proportional to approximately the third power of the turbulent velocity of the product flowing through the homogenizer channel, which in turn is directly proportional to the applied pressure.
• Thus, the higher the pressure, the higher the efficiency of disruption each run through the machine.
• The operational parameters which impact the efficiency of high- pressure homogenizers are as follows:
  • Pressure
  • Temperature
  • Number of passes
  • Valve and impingement design
  • Flow rate

What is High Pressure Homogenizer?

• A high pressure homogenizer is a machine that uses high pressure to emulsify, mix, or break down substances. It typically works by forcing a fluid through a small orifice or valve at high pressure, creating a high-energy impact that can break down particles or droplets in the fluid. This technology is commonly used in the food and beverage industry, as well as in pharmaceuticals and biotechnology, to create stable emulsions and suspensions, and to reduce the size of particles in a fluid. High pressure homogenizers can also be used to sterilize liquids, as the high pressure can kill microorganisms.
• High pressure homogenizers are important in many industries due to their ability to create stable emulsions and suspensions, and to reduce the size of particles in a fluid. This can improve the appearance, texture, and shelf-life of a product, as well as increase its bioavailability.
• In the food and beverage industry, high pressure homogenizers are used to create homogenous mixtures of liquids, such as milk and cream, and to create stable emulsions, such as salad dressings and mayonnaise. They can also be used to reduce the particle size of solids, such as cheese, to create a smoother texture.
• In the pharmaceutical and biotech industries, high pressure homogenizers are used to create stable suspensions and emulsions of drugs, as well as to reduce the particle size of drugs to increase their bioavailability. They can also be used to sterilize liquids, as the high pressure can kill microorganisms.
• In the cosmetics industry, high pressure homogenizers are used to create stable emulsions of oils and water, such as lotions and creams, and to reduce the particle size of pigments and other solid ingredients to improve the appearance and texture of the final product.
• Overall, High pressure homogenizers are versatile and efficient machines that can be used to improve the quality and stability of a wide range of products in various industries.
• Over the years, numerous theories on the mechanism of high pressure homogenization have been suggested. For a low-viscosity oil-in-water dispersion, such as milk, where the majority of droplets have a diameter on the order of 1 m (10–6 m), two ideas have persisted. Together, they provide an excellent description of how various parameters affect the homogenising impact.
• The notion of globule disruption by turbulent eddies (also known as “micro whirls”) is based on the formation of a liquid jet at the gap’s outflow. As the jet fragments, numerous minor eddies are produced. Faster pressure equals higher jet velocity, which results in fewer, more energy-dense eddies. If an eddy collides with an oil droplet of roughly the same size, the droplet will deform and eventually disintegrate. This hypothesis predicts the relationship between the homogenising effect and the homogenising pressure. Numerous studies have established this relationship.
• According to the cavitation theory, the fat droplets are disrupted by the shock waves released when the steam bubbles implode. According to this idea, homogenization occurs when the liquid leaves the gap; hence, the back pressure that is necessary to regulate cavitation is also necessary for homogenization. This has been demonstrated in practice. However, homogenization is feasible without cavitation, albeit at a lower efficiency.

Working principle of high pressure homogenizer

High-pressure homogenization involves the use of high-pressure, compressed liquid material that flows through the gap at high speeds and is subjected to intense shear stresses. The collision of the liquid material on the metal ring generates a powerful impact force and an explosive force induced by the quick drop and rise in static pressure. With the use of comprehensive force, the transformation of the initial coarse emulsion or suspension into a very fine, stable emulsion or suspension.

When the homogenous material passes through the adjustable gap h (typically 011 mm) between the valve seat and the valve stem, the gap accelerates to 200 300 m/s in a split second, resulting in a significant pressure reduction. If the pressure falls to At the operating temperature, the saturated vapour pressure (or air separation) of a large number of micro-bubbles lowers the distance between the liquid and the gap outlet, hence increasing the pressure.

When the pressure reaches a particular level, the liquid begins “boiling,” rapid “vaporisation,” and the formation of a high number of bubbles. A phenomena is created when the bubbles in a liquid rapidly burst and re-condense, and a vast number of bubbles are made and burst in an instant. The phenomena appears to be an abundance of small zha bombs. Strong energy discharge generates profound high-frequency vibrations.

Simultaneously, the strong shear force caused by the strong turbulence, the softness of the liquid, the presence of semi-soft particles in the mixture, and the turbulent shearing all contribute to the instability of the fluid. Under the combined action of force and size, the force is fragmented into particles. The pulverised particles then made high-speed contact with the impact ring, where they were further pulverised and distributed.

• It is most widely used method for preparing nanosuspensions of many poorly aqueous soluble drugs. It involves three steps. 
• Firstly drug powders are dispersed in stabilizer solution to form pre-suspensions. 
• Secondly the pre-suspension is homogenized in high pressure homogenizer at a low pressure for premilling. 
• Finally homogenized at high pressure for 10 to 25 cycles until the nano-suspensions of desired size are formed.

Homogenization Mechanism

Two theories are proposed for high pressure homogenization

• Cavitation theory 
• Globule disruption by turbulent eddies (“micro whirls”) 

1. Cavitation theory

• The liquid encounters strong cavitation because of the large pressure drop via the valve. When the pressure drop is big enough, the vapour pressure of the liquid surpasses the ambient pressure triggering development of vapour bubbles (cavities in the liquid) (cavities in the liquid).
• When the cavitation bubbles rupture (collapse of the cavities), shock waves are generated in the liquid. These shock waves split apart the distributed droplets.

2. Globule disruption by turbulent eddies (“micro whirls”) 

• The notion of globule disruption by turbulent eddies (also known as “micro whirls”) is based on the formation of a liquid jet at the gap’s outflow.
• As the jet fragments, numerous minor eddies are produced.
• Faster pressure equals higher jet velocity, which results in fewer, more energy-dense eddies.
• If an eddy collides with an oil droplet of roughly the same size, the droplet will deform and eventually disintegrate.
• This hypothesis predicts the relationship between the homogenising effect and the homogenising pressure.

Working of High Pressure Homogenizer

• The non-homogenized product enters the valve seat with low velocity and high pressure.
• As the product enters the (adjustable) narrow clearance between the valve and the seat, its velocity and pressure rapidly increase and decrease, respectively.
• The particles are torn apart by turbulence and localised pressure differences caused by the tremendous energy release.
• The homogenised product strikes the impact ring and exits at a sufficient pressure for progression to the next stage.

Homogenization valve Assembly 

• Homogenizers can have a single valve assembly (single-stage) or two valves connected in series (two-stage).
• For the majority of items, a single-stage valve is adequate. A two-stage assembly that applies less than 10% of the total pressure to the second stage regulates back pressure and reduces clumping.
• This enhances the droplet size reduction and the particle size distribution narrowing. When great homogenization efficiency is desired, two-stage homogenization is typically employed.

Physical Process inside the homogenization valves 

• On entering the homogenization valve, the flow speed greatly increases → pressure drops (Bernoulli) to reach the vapor pressure P_D at point A.
• Since P_D is lower than the external pressure P_A → cavitation and two phase fluid flow.
• Pressure signal transduction in multi-phase flows is slower than in single phase flow → equilibration with external pressure occurs late (close to exit).
• Sudden pressure jump leads to collapse of cavitational bubbles and the flow reverts to a one-phase flow
• Droplet disruption is therefore due to 
  • Laminar and turbulent flow at entrance of valve (a) 
  • Growth of cavitational bubbles in zone (b) 
  • Collapse of bubbles in zone (c)

Homogenization in Aqueous media (Dissocubes) 

• Forcing the of the suspension under pressure through a narrow aperture valve. 
• Dissocubes was developed by Muller et al in 1999. 
• This instrument can be operated at pressure varying from 100-1500 bars (2800-21300 psi).
• It is the most widely used method for the preparation of nanosuspensions of many poorly water soluble drugs. Dissocubes are engineered using Piston-gap-type high pressure homogenizers. 
• A commonly used homogenizer is the APV Micron LAB 40. However, other piston-gap homogenizers from Avestin and Stansted can also be used Gap. 
• A high-pressure homogenizer consists of a high pressure plunger pump with a subsequent relief valve (homogenizing valve). 
• The task of the plunger pump is to provide the energy level required for the relief. The relief valve consists of a fixed valve seat and an adjustable valve. These parts form an adjustable radial precision gap. The gap conditions, the resistance and thus the homogenizing pressure vary as a function of the force acting on the valve

Principle of Dissocubes 

• Particle size reduction in piston gap homogenizers is based on the cavitation principle. Particles are also diminished as a result of significant shear forces and collisions between particles.
• The dispersion enclosed in a cylinder with a 3 cm diameter abruptly travels through a 25 m-wide slit.
• According to Bernoulli’s Law, the liquid flow volume per cross section in a closed system is constant. The drop in diameter from 3 centimetres to 25 micrometres causes an increase in dynamic pressure and a decrease in static pressure below the boiling point of water at ambient temperature.
• As a result, water begins to boil at ambient temperature and generates gas bubbles, which implode when the suspension leaves the gap (known as cavitation) and normal air pressure is achieved.
• The achievable size of drug nanocrystals is primarily determined by temperature, number of homogenization cycles, homogenizer power density, and homogenization pressure.

Homogenization in Non-Aqueous media (Nanopure)

• The drug suspensions in the non- aqueous media were homogenized at 0^oC or even below the freezing point and hence are called Deepfreeze homogenization 
• Advantages: 
  • Evaporation is faster and under milder conditions. 
  • This is useful for temperature sensitive drugs. 

Types of High Pressure Homogenizer

Types of High Pressure Homogenizer By energy source

1. Electric

An electric motor powers electric homogenizers. This homogenizer category can be further broken into two types: direct-drive and intensifier.

• Direct-drive type: The motor drives the crankshaft to reciprocate the plunger, directly applying pressure on the material. Multiple plungers on the crankshaft collaborate to generate consistent pressure and a high flow rate; vast volumes of materials are necessary to generate constant pressure. The motor requires a multi-stage gear reduction mechanism to drive the crankshaft, which makes the equipment bulky. The homogenizer with a crankshaft is appropriate for low-pressure, large-scale manufacturing applications.
• Intensifier type: In intensifier-type high pressure homogenizers, the motor presses the material through the interaction chamber by driving the intensifier. The intensifier system may generate a higher pressure, hence enhancing the efficiency of the homogenization procedure. Compared to the homogenizer with a crankshaft, the homogenizer with an intensifier has a lower flow rate, requires less material, and has a greater pressure. It can be utilised for laboratory applications involving small sample volumes and industrial applications involving high pressure. When fitted with a diamond interaction chamber, the electric high pressure homogenizer with an intensifier is categorised as a premium homogenizer. This type is commonly used in laboratories for biology, pharmaceuticals, and nanotechnology. The conventional intensifier is hydraulic, but a new type of electric cylinder with a linear actuator is more effective.

2. Hand Driven

Manually powered homogenizers provide pressure on the material. A hand homogenizer has a low flow rate, but it is portable and simple to instal and disassemble. It is useful for small-scale investigations because to the minimal amount of materials required. This type of gadget is capable of meeting the research and development requirements of biopharmaceutical laboratories. Manual high-pressure homogenizers are also known as Handgenizers.

3. Air Driven

The air-powered homogenizer transfers compressed gas pressure to hydraulic pressure. Therefore, it requires a nitrogen cylinder or an air compressor for assistance. This homogenizer has a high gas consumption, significant noise levels, and a relatively low maximum homogenization pressure. Due to the absence of a separate intensifier pump structure, its volume is modest, and it is suited for sites with compressed nitrogen.

Types of High Pressure Homogenizer By principle and structure of the interaction chamber

1. First Generation: Impact Type

• Cavitation nozzles: The primary function of this nozzle is cavitation, which separates the emulsion and increases particle size. The materials flow into the cavitation nozzle with a very small aperture at several times the speed of sound under the pressure of the homogenizer. In the meantime, there is strong friction and impact between the particles and the metal valve components. This friction decreases the equipment’s service life, and the impacts cause metal particles to enter the final goods.
• Impact valve: Using tungsten alloy materials, the impact valve and impact ring structure moderately reduce local wear and extend the homogenization chamber’s service life. The impact valve’s function is a combination of impact and cavitation. Nonetheless, its fundamental idea is the collision of the suspended substance with the structure of a high-hardness metal (such as tungsten alloy). Consequently, the impact valve cannot resolve the issue of metallic particle residue. In the first decade of the 20th century, the majority of high-pressure homogenizers included an impact valve.

2. Second Generation: Interaction Type (Y-type interaction chamber)

Several firms in the United States have utilised the Y-type interaction chamber, considered one of the most effective homogenization chambers to date. In these systems, the flow stream is divided into two channels, which are then redirected at right angles over the same plane and driven into a single flow stream. A high pressure encourages a high velocity at the intersection of the two flows, resulting in severe shear, turbulence, and cavitation over the single outgoing flow stream.

With the distinctive Y-type structure, the high-velocity moving materials in the high-pressure solution clash with each other, a process that significantly increases the chamber’s service life compared to conventional designs. Utilizing diamond material inhibits metal particle residual generation.

Because it minimises cavitation and produces excellent, stable particle size and PDI (poly dispersity index) control ability, the Y-type interaction chamber is commonly employed in the manufacturing of pharmaceutical emulsions. The major manufacturers of the diamond interaction chamber are Genizer and Microfluidics Corp. Currently, the Y-type diamond interaction chamber is mostly utilised in high-end nanotechnology and accounts for more than 90% of the US pharmaceutical sector. The temperature-controlled interaction chamber of Genizer prevents temperature spikes and enables up to 60,000 psi of working pressure.

Low emulsification efficiency and metallic particle residue are two issues generated by impact-designed homogenization chambers. During the manufacturing of pharmaceutical injections, inert metallic particles are generated when particles clash with internal metal components. These metallic particles might combine to generate larger particles. In pharmaceutical applications, this is a problem since large particles reduce capillary blood flow, which in turn causes mechanical damage to human tissues, resulting in acute or chronic inflammation. The interaction chamber eliminates particle residue and demulsification issues. However, because of the chamber’s internal structure, when the concentration and viscosity of the product are high, the chamber is more likely to produce flow blockage than impact homogenizers.

Types of High Pressure Homogenizer By principle of pressurization

To achieve high pressure levels, the ultra-high pressure homogenizer requires a considerable thrust to propel the piston in the cylinder. The rotating motor must reduce speed, increase torque, and convert linear motion to linear reciprocating motion with high thrust in order to obtain linear reciprocating motion. The pressurisation principle acts differently in homogenizers of the direct-drive and intensifier types.

1. Direct-drive type

The motor drives the crankshaft to reciprocate the plunger and directly apply pressure to the material. Multiple sets of plungers generate consistent pressure, and the homogenizer’s flow rate is high. However, both the minimal material requirements and the amount of residue produced are significant.

The motor-driven crankshaft of these homogenizers requires a multi-stage gear reduction mechanism, limiting their efficiency and necessitating huge unit dimensions. This type of homogenizer is appropriate for use in the food and chemical industries, as well as other low-pressure applications.

2. Intensifier type

The intensifier-type homogenizer is the outcome of recent technological advancements in ultra-high pressure. The motor operating the oil pump to pressurise the material through the hydraulic system is one of its mechanisms. The hydraulic system provides greater pressure than direct-drive homogenizers, but the volume and minimum material demand are reduced. The intensifier-type homogenizer is applicable to both high-pressure laboratory and industrial homogenizers.

The hydraulic intensifier may accomplish low-frequency and high-thrust piston movement, which extends the machine’s service life and saves its maintenance expenses. Using parallel four-cylinder technology, ultra-high pressure of up to 45,000 psi can be maintained without the use of an accumulator.

In the past, the majority of high pressure homogenizers were direct-drive models, despite the apparent disadvantages of this design. It has a short service life and requires frequent maintenance on its wearing parts, especially when the pressure exceeds 100 MPa. Hydraulic homogenizers are expensive to manufacture, but they have a long service life and require little wear-parts maintenance.

Parts of High Pressure Homogenizer

A high pressure homogenizer typically has several key parts, including:

1. A high pressure pump: This generates the high pressure needed to homogenize the sample.
2. A homogenization valve: This regulates the flow of the sample and controls the pressure at which it is homogenized.
3. A homogenization chamber: This is where the sample is subjected to high pressure, causing it to be homogenized.
4. A cooling system: This is used to cool the sample and prevent overheating during the homogenization process.
5. A pressure gauge: This measures the pressure inside the homogenizer.
6. A control panel: This allows the operator to adjust the settings of the homogenizer, such as pressure and flow rate.
7. A pressure relief valve: This releases excess pressure to prevent damage to the homogenizer.
8. An inlet and outlet: These are used to feed the sample into the homogenizer and to remove the homogenized sample from the homogenizer.

Applications of High a Pressure Homogenizer

High pressure homogenizers are used in a variety of industries and applications, including:

1. Food and Beverage Processing: Homogenization is used to create emulsions, such as salad dressings and mayonnaise, and to reduce particle size in products like milk and juice.
2. Pharmaceuticals: Homogenization is used to create stable suspensions and emulsions of drugs, and to improve the bioavailability of drugs by reducing particle size.
3. Biotechnology: Homogenization is used to break open cells and release intracellular content for downstream processing in applications such as cell lysis, protein extraction and purification.
4. Cosmetics: Homogenization is used to create stable emulsions for lotions, creams, and other personal care products.
5. Chemical and Petroleum: High pressure homogenization is used to create stable emulsions for chemical reactions, and to reduce particle size of suspensions in oil drilling.
6. Environmental: High pressure homogenization is used in the treatment of industrial effluents and municipal wastewater.
7. Biomedical: High pressure homogenization is used to prepare samples for analysis in biomedical research, such as the isolation of specific cell types or the preparation of samples for microscopy.

Advantages of High a Pressure Homogenizer

High pressure homogenizers offer several advantages over traditional homogenization methods, including:

1. High Efficiency: High pressure homogenization can produce smaller and more consistent particle sizes than traditional methods, resulting in a more homogeneous final product.
2. High Throughput: High pressure homogenizers can process large volumes of sample quickly, making them suitable for industrial and large-scale applications.
3. High-pressure sterilization: High-pressure homogenization can inactivate microorganisms such as bacteria, viruses and spores, making it a good alternative to traditional sterilization methods such as heat and chemicals.
4. Flexibility: High pressure homogenizers can be used with a wide variety of samples, including liquids, suspensions, and emulsions, making them versatile for different applications.
5. Energy efficient: High pressure homogenization process is more energy efficient than traditional methods that use mechanical force or high-energy inputs.
6. Cost-effective: High pressure homogenization process can be more cost-effective than other methods, such as ultrasonication, in terms of both equipment and operating costs.
7. Safety: High pressure homogenization is a relatively safe process, it does not generate heat or create a risk of fire and explosion.

Disadvantages of High a Pressure Homogenizer

While high pressure homogenizers offer many advantages, they also have some limitations and disadvantages, including:

1. High cost: High pressure homogenizers can be expensive to purchase and maintain, making them less accessible for some users.
2. Complexity: High pressure homogenizers can be complex to operate and maintain, requiring specialized training and knowledge.
3. Sample size: High pressure homogenizers typically require larger sample sizes than other methods, which can be limiting for some applications.
4. Sample compatibility: High pressure homogenization may not be suitable for certain types of samples, such as heat-sensitive samples or samples that are prone to oxidation.
5. Shear sensitivity: High pressure homogenization can cause some damage to sensitive samples, such as cells and enzymes, due to the high shear forces involved in the process.
6. Noise: High pressure homogenizers can be quite loud during operation, which can be a concern in some lab settings or when working with sensitive samples.
7. Equipment maintenance: High pressure homogenizers require regular maintenance and cleaning to maintain optimal performance and safety.
8. High pressure pump maintenance: High pressure pumps used in homogenization are prone to wear and tear and need regular maintenance and service to keep running smoothly.

References

• Chen, Qishen & Xue, Feng & Ding, Enyong. (2019). Preparation of POSS-triol/wollastonite composite particles by Liquid phase mechanochemical method and its application in UV curable coatings. Science and Engineering of Composite Materials. 26. 183-196. 10.1515/secm-2019-0001.
• Chen, Qishen & Xue, Feng & Ding, Enyong. (2019). Preparation of POSS-triol/wollastonite composite particles by Liquid phase mechanochemical method and its application in UV curable coatings. Science and Engineering of Composite Materials. 26. 183-196. 10.1515/secm-2019-0001.
• Bonthagarala, Brahmaiah & Balamarkonda, CH & Rao, V & Adamkhan, Patan & Sreekanth, Dr. Nama. (2013). A REVIEW ON SIGNIFICANCE OF NANOCRYSTALS IN DRUG DELIVERY. International Journal of Pharmacy. 3. 56-61.
• https://dairyprocessinghandbook.tetrapak.com/chapter/homogenizers
• https://www.slideshare.net/AnilPethe/high-pressure-homogenization-107148064
• https://www.sciencedirect.com/topics/engineering/high-pressure-homogenisation#:~:text=The%20principle%20behind%20high%2Dpressure,11.3).
• https://www.slideshare.net/AnilPethe/high-pressure-homogenization-107148064
• https://www.solidswiki.com/index.php/High_Pressure_Homogenizers
• https://homogenizers.net/pages/ac-high-pressure-homogenization
• https://www.pmg.engineering/high-pressure-homogenization/
• https://www.scientzbio.com/info/working-principle-of-high-pressure-homogenizer-44061763.html