Optimization of Process Parameters of High-Pressure Homogenizer

A high-pressure homogenizer (HPH) is a device utilized in the pharmaceutical industry for size reduction, mixing, and stabilization of dispersions, including macroemulsions, microemulsions, and suspensions. It generates extremely high local stresses, resulting in a significant reduction in particle size. Continuous production under large-scale conditions makes this type of equipment suitable for scale-up processes. In HPH, a liquid is passed through a narrow gap under high pressure. The liquid fed into the homogenizer can be a macroemulsion, microsuspension, or dispersion, commonly referred to as a premix. Depending on the available equipment, the HPH operates at pressures ranging from 50 to 500 MPa. Among these, homogenizers that can operate at pressures of 200 MPa and above are classified as ultra-high pressure homogenizers (UHPH). Pressure units include MPa, psi, and bar. The homogenization pressure is essential for forcing the liquid through the narrow gap, and the sudden passage of the premix through the narrow cavity under high pressure causes size reduction and droplet breakup.

During the process of liquid passing through a high-pressure homogenizer, the liquid assembles molecules in various configurations. These molecules interact with both the liquid and solid at the interface, altering the molecular dynamics of the liquid. The molecular dynamics provide insights into the coexistence of numerous interfacial phenomena that occur simultaneously or in parallel. Investigating these interfacial phenomena is crucial for maintaining product quality consistency, particularly in the development of new drug delivery systems. Although nanodrug delivery systems are well-known for their unique characteristics—such as protecting drug moieties, controlling release through encapsulation, enabling dual drug loading, reducing size, and increasing surface area—a significant number of batch failures occur during scale-up. This issue arises from insufficient attention to each process parameter and a lack of research on the interdependence of these parameters. Therefore, it is essential to employ Design of Experiments (DoE) and Quality by Design (QbD) methodologies to ensure consistent parameters across each batch and to investigate the interrelationships among the parameters.

The importance of understanding the process parameters of high-pressure homogenizers is crucial, as these variables significantly influence various physicochemical characteristics, including particle size, surface charge, and polydispersity index (PDI). These characteristics, in turn, affect the stability and cellular uptake of nanoparticles. By optimizing the physicochemical properties of nanoparticles, it is possible to enhance the efficacy of drug release from nanosuspensions, nanoemulsions, or self-nanoemulsifying drug delivery systems.

Parameters Affecting the Process

Homogenization Pressure

Homogenization pressure refers to the pressure at which a liquid is forced through a narrow gap, typically ranging from 10 to 500 MPa. During this process, the liquid droplets experience shear, cavitation, and turbulence, which contribute to their fragmentation into smaller droplets. Droplets will only break apart when the shear force is sufficient to overcome the Laplace pressure. An increase in homogenization pressure generates stronger vortices, further facilitating the reduction of droplet size. Additionally, higher pressure results in a greater pressure drop, which can effectively surpass the Laplace pressure, leading to further size reduction. Consequently, homogenization pressure has a direct impact on particle size through turbulence, making it a critical process parameter. Force density also becomes an essential parameter to adjust in order to achieve the desired average particle size.

The Number of Passes and Time

Under specified pressure conditions, the collected premix is recirculated through the narrow gap, completing one pass. As the liquid undergoes shear, cavitation, and turbulence again, the droplet size is further reduced. Consequently, under constant pressure conditions, the number of passes or recirculations is directly related to the average droplet diameter. The time required to complete a pass depends on the viscosity of the liquid. As the droplet size decreases, the viscosity of the emulsion diminishes after two or three passes, thereby reducing the time needed to complete each pass.

Fluid Dynamics

In certain product lines, the fluid dynamics within pilot and production-scale homogenizers may differ slightly due to the increased gap height in production-scale homogenizers. For high-pressure homogenizers, whether at the production or pilot scale, that utilize three or five piston pumps, the resulting pulses are minimal, leading to only slight oscillations in the flow field. This phenomenon does not impact efficiency and indicates that studies on production and pilot-scale high-pressure homogenizers support continuous inflow. Conversely, in laboratory-scale equipment, the pulses are significant enough to alter the flow field. When all other parameters remain constant, these pulses are expected to enhance the efficiency of breakdown, as the flow rate is higher during passage through the gap. Therefore, when translating results from laboratory to production-scale high-pressure homogenizers, it is essential to consider the variability inherent to each scale.

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.