High-pressure homogenization (HPH) was first developed in the early 20th century by Auguste Gaulin for processing milk, utilizing pressures of up to 30 MPa to enhance product stability. The fundamental working principle of HPH has remained consistent, involving the use of a high-pressure pump to force fluid through small orifices. The initial success of HPH has broadened its user base, establishing it as a comprehensive unit operation for liquid product handling across various industries, including food and beverage, pharmaceuticals, wastewater treatment, materials production and processing, and bioprocess technology. The application areas for HPH are likely to continue expanding.
As new HPH applications emerge, significant efforts are required in both industry and academia to enhance our understanding of the impact of HPH processes. Various studies have examined the theoretical aspects of homogenization processes, including fluid flow in HPH valves and the mechanisms underlying complex processes such as emulsification. Additionally, research has focused on the operational aspects of HPH, exploring methods for process optimization and improving monitoring and characterization techniques. Recent equipment innovations, such as the development of new homogenization valve geometries and ultra-high pressure homogenization (UHPH) with pressures ranging from 300 to 400 MPa, demonstrate the ongoing advancements made by equipment manufacturers. This article will provide a brief overview of the typical and innovative applications of HPH across various fields, specifically highlighting three main areas: 1) food and beverages, 2) pharmaceuticals and biotechnology, and 3) materials and chemicals. The specific applications within each field are:
Food and beverage:
Functional food
Food additives
Alternative food
Pharmaceuticals and Biotechnology:
API processing
Excipient processing
Therapeutic nanoparticles
Cell disruption
Materials and chemicals:
Carbon nanotube/graphene
Nanofluids
Polymer
Nanocellulose
When utilizing HPH for new applications, it is essential to evaluate not only the relevance and appropriateness of homogenization effects for the intended application but also to consider the following factors to assess feasibility: a) pumpability, b) energy consumption, and c) the service life of wear parts (e.g., homogenizer/pump valves and gaskets/O-rings). The first factor pertains to the technical feasibility of operating the HPH process; raw materials with characteristics such as high viscosity or large, hard particles are often difficult to pump and may not be reliably fed into the homogenizer. Additionally, two other factors that influence the commercial viability of the HPH process are excessive energy consumption and/or significant wear of consumable parts, which can result in increased costs and production downtime.
Food and Beverage
With its origins in the food and beverage industry, HPH continues to operate as a comprehensive unit in various well-established applications, including ensuring food safety and enhancing the physical and chemical properties of food products, such as juices and dairy items. Consequently, numerous studies are still investigating areas that require improvement within these traditional applications.
In addition to concerns about food sustainability and climate change, alternative food innovations, including plant-based dairy and meat, lab-grown meat, precision-fermented proteins, and insect proteins, are gaining traction among both consumers and commercial entities. The application of HPH in alternative food products is functionally comparable to that in conventional foods, as both require similar processing objectives, such as enhanced product stability and sensory attributes, improved structural and physicochemical properties, and better processing characteristics. The similarities in processing goals, technical requirements, and implementation strategies contribute to the advancement of these alternatives, as extensive prior knowledge in conventional food processing aids in the development and scaling of alternative food production.
HPH has recently been utilized to convert meat waste into nutritional and functional products, which could enhance the sustainability of the meat industry. The intense force generated by the HPH valve can significantly alter the protein structure, leading to myofibril destruction, depolymerization, and protein unfolding. These changes result in substantial modifications to the physicochemical properties of the protein, including surface hydrophobicity and charge, thereby improving various functional properties such as solubility and foaming ability. Additionally, HPH facilitates the effective dispersion of additives, such as biopolymers, with proteins, enhancing properties like colloidal stability and film water vapor permeability. The improvements achieved through HPH enable low-value meat proteins, which might otherwise be discarded, to be transformed into high-value products.
HPH is also utilized to develop and produce innovative food products that offer optimized health benefits, such as functional foods, which frequently possess enhanced sensory properties and stability. Nanoemulsions—dispersions of two immiscible liquids emulsified with droplets measuring approximately 100 nm—play a significant role in this trend. These nanoemulsions enhance product appearance and stability, protect sensitive compounds, and improve the bioavailability of functional ingredients by incorporating lipophilic components.
Pharmaceutical and Biotechnology
The recent widespread use of HPH in the pharmaceutical industry is based on their established capabilities in new applications and improvements to existing products and processes. Broadly speaking, the pharmaceutical applications of HPH can be categorized into two main areas: the processing of excipients, particularly polymer types, and active pharmaceutical ingredients (APIs), specifically nanoparticle systems, aimed at enhancing drug delivery.
Processing of Excipients: Polymers and gums, such as alginates and cellulose derivatives, are common pharmaceutical excipients utilized in drug delivery systems. These polymeric systems are widely employed as thickeners or stabilizers in drug delivery and tissue engineering vehicle liquids, suspensions, or transdermal products. HPH is frequently used in the production and modification of these polymers. In oral solid dosage forms, polymer excipients also serve as fillers, binders, and disintegrants. HPH is often applied to modify polymers and gums because it can alter their properties through intense high shear and turbulence. This process can lead to changes in rheological properties, viscosity reduction, zeta potential, molecular weight, and fluid dynamics. The reduction in particle size enhances processing properties and enables innovative formulation strategies, such as incorporating highly viscous polymer gels into formulations or improving product quality by increasing film strength and water resistance.
Processing of APIs: The ability of HPH to reduce the size of APIs can impart a variety of beneficial properties to the final drug product. One particularly noteworthy application is the formation of API nanocrystals and nanosuspensions. By preparing the API as a nanosuspension, solubility can be enhanced, thereby improving the bioavailability of poorly soluble drugs. This improvement in drug solubility enables the commercialization of drugs that were previously deemed unfeasible due to their poor solubility. While this approach is not new, increasing research is focusing on better understanding the relationship between product and process, including the impact of formulation selection, HPH operating conditions, and process type and configuration. Another noteworthy application of HPH in API processing is the preparation of nanoemulsions. Hydrophobic drugs are dissolved in an oil phase and subsequently emulsified into oil-in-water (O/W) nanoemulsions for use in various drug delivery systems, such as sprays, creams, and capsules. The advantages of drug nanoemulsions include enhanced bioavailability, improved stability, and controlled release. Beyond the pharmaceutical field, recent research on different aspects of the nanoemulsion process has contributed to a better understanding of both process and product through the optimization of emulsifier types and concentrations, HPH operating conditions, equipment design, and process configurations. Many insights from these studies offer valuable guidance for utilizing HPH in the preparation of nanoemulsions within the pharmaceutical and related industries.
Nanoparticle Systems: Nanoparticle systems play a crucial role in the pharmaceutical industry, serving as a vital platform to achieve various clinical and therapeutic objectives, such as targeted drug delivery and the development of effective and safer imaging agents. HPH has emerged as a viable method for processing three types of nanoparticle systems: lipid nanoparticles, polymer nanoparticles, and inorganic/hybrid nanoparticles. The application of HPH in the processing of therapeutically relevant nanoparticles is on the rise. Most literature focuses on the development of nanoparticle products and formulations of different APIs, using lipid and polymer nanoparticles for gene therapy, molecular targeting agents, and imaging agents. The use of HPH in nanoparticle production has been extensively investigated by the industry, providing valuable insights for scale-up, process control, and optimization.
Biopharmaceutical and Biotechnology: Biopharmaceutical and biotech applications involving HPH rely on its proven cell disruption/lysis capabilities. These applications include the development of cell-free protein systems using various cell types in both batch and continuous modes, downstream processing to produce recombinant proteins and virus-like particles, and the extraction of oils and other products from algae. Current research focuses on analyzing the specific nuances of these processes and products to identify methods for enhancing efficiency, quality, and control. This research encompasses the study of interactions between upstream and downstream unit operations on inclusion body quality and yield, the improvement of monitoring strategies for cell disruption processes, and the optimization of overall process strategies.
Advanced Materials and Chemical Applications
Polymer Production and Processing: Natural biopolymers are being investigated as alternative and sustainable materials for various applications, including substitutes for synthetic polymers, therapeutic uses, and electronic materials. HPH, combined with other techniques such as enzymatic hydrolysis, has been effectively employed in the production of biopolymers, including nanocellulose, starch nanoparticles, chitin nanofibers, and silk nanofibers. Typically, natural biopolymers lack the physicochemical properties necessary for further processing or for use in final products. Therefore, chemical treatments to modify rheological properties or the addition of modifiers, such as plasticizers, to create composites may be required. In most instances, HPH is primarily utilized to produce the target material, which is subsequently processed using additional techniques.
In certain instances, HPH is utilized for subsequent modification and processing steps, including the modification of starch nanoparticles, rheological and structural modification of polymer dispersions, and the formation of nanofibrillated cellulose composites. Nanocellulose, a cellulosic material at the nanoscale, warrants special attention and is available in three primary forms: nanocrystalline cellulose, bacterial nanocellulose, and nanofibrillated cellulose (NFC). Various types of nanocellulose have garnered significant interest from the industry due to their numerous advantageous properties, such as being a biodegradable natural product with high strength and stiffness, as well as the potential for surface chemical modification. Nanocellulose has found applications across multiple fields, including food, composites and packaging, electronics, biomedicine, and pharmaceuticals. HPH has emerged as a convenient, scalable, and relatively environmentally friendly technology for processing and producing nanocellulose and its derivatives. The application of HPH induces a range of physicochemical changes in cellulose, including internal and external fibrillation, a reduction in average particle size and crystallinity, and alterations in molecular weight distribution due to the scission of long polymer chains. The intense shear forces generated during the HPH process are believed to be the primary mechanism of action.
Nanoscale Materials and Fluids: HPH has been utilized for the large-scale production of various nanomaterials, including boron nitride nanosheets, transition metal dichalcogenide nanosheets, and graphene along with its derivatives, through liquid-phase exfoliation. Subsequent applications of these nanomaterials often necessitate their dispersion in a suitable medium; in some instances, the dispersion generated during the liquid-phase exfoliation process can be used directly. Consequently, HPH is well-suited for the direct production of a wide range of dispersions and has proven to be an effective technique for both dispersing and potentially modifying nanomaterials. Numerous studies have successfully employed HPH as a processing step to create advanced materials, such as graphene films and inks, polymer composites that incorporate nanomaterials to enhance mechanical, thermal, and electrical properties, and nanofluids. One application of particular interest is the production of graphene/carbon nanotube slurries for battery electrode coatings, which has recently gained significant traction in the industrial sector.
Nanofluids consist of various types of nanoparticles, including metal nanoparticles, their oxides, and carbon-based materials such as carbon nanotubes and graphite, suspended in a base fluid. These fluids have emerged as a promising class of advanced thermal fluids capable of enhancing heat transfer performance and thermal efficiency in applications such as engine cooling and building temperature management systems. HPH has been successfully employed to produce nanofluids containing carbon nanoparticles, including carbon nanotubes, diamond, graphite, and graphene, as well as metal oxides. Additionally, the homogenization process has been utilized in the production of phase change material emulsions, which are currently under investigation as advanced thermal fluids and energy storage media.
Since its establishment, Antuos Nanotechnology (Suzhou) Co., Ltd., a Duoning company, has been dedicated to independent research and development, as well as the introduction of advanced pharmaceutical equipment and technologies. The company provides cutting-edge pharmaceutical equipment solutions for both of scientific research institutions and pharmaceutical companies. It has received positive feedback from customers worldwide and has become a preferred choice for many users.
Antuos High Pressure Homogenizers from Lab-Scale to Production Scale
Antuos Nanotechnology (Suzhou) Co., Ltd. specializes in nanotechnology, bioengineering, and nanochemical technology. Our primary products are utilized in the research, development, and production of liposome drugs, microsphere-based drugs, vaccines, diagnostic reagents, and more. We offer a comprehensive range of high-pressure homogenizers and are recognized as a leader in high-pressure homogenization technology. Antuos's products have been extensively adopted by major scientific research institutions and pharmaceutical companies worldwide, spanning various industries, including the biological sector (protein drugs, diagnostic reagents, enzyme engineering, human vaccines, veterinary vaccines, etc.), the nanotechnology industry (fat emulsions, liposomes, nanoparticles, microspheres, etc.), the food industry (beverages, dairy products, food additives, etc.), and the chemical industry (new energy batteries, nanocellulose, coatings, papermaking, polymer materials, etc.). Currently, we serve over 1,000 end users, providing thousands of systems, with dozens of systems utilized for commercial production.
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