High-Pressure Homogenizer Applications in Pharmaceutical Industry

High-pressure homogenizers are extensively utilized in the pharmaceutical industry due to their versatility. This technology enhances bioavailability by reducing particle size, increases drug delivery, and improves stability and shelf life through homogeneous dispersion and reduced chemical degradation. Additionally, it helps ensure consistent product quality. By addressing these critical factors, high-pressure homogenizers play a vital role in the development and production of safe, effective, and high-quality pharmaceutical products. In this article, we will explore some typical applications of high-pressure homogenization in the pharmaceutical industry.

Nanoparticle Size Reduction

High-pressure homogenizers are primarily utilized for particle size reduction in the pharmaceutical industry. They employ pressure to break down granules and globules in a premix into uniformly sized particles. This technology is often preferred because it is effective for both aqueous and non-aqueous feeds, addressing the limitations of traditional ball milling methods, which can lead to high levels of amorphization, polycrystallization, and metal contamination. Reducing particle size not only decreases the required dosage, thereby minimizing side effects, but also enhances bioavailability and dissolution characteristics.

Improved Solubility and Bioavailability

Previous studies have demonstrated that high-pressure homogenizers can enhance the dissolution rate and bioavailability of BCS Class II drugs, such as spironolactone, budesonide, and omeprazole, by effectively reducing particle size to the nanoscale. Additionally, the application of high-pressure homogenizers in the preparation of nifedipine nanoparticles has successfully improved both the dissolution rate and saturated solubility. Furthermore, a study utilized antisolvent precipitation combined with high-pressure homogenization to prepare celecoxib nanoparticles. The results indicated that celecoxib samples produced using high-pressure homogenization exhibited superior solubility properties compared to those prepared via the antisolvent precipitation method. This enhanced solubility is attributed to the conversion to a more stable crystalline form following treatment with a high-pressure homogenizer.

The bioavailability and dissolution rate of poorly water-soluble drugs are often low. In such cases, reducing the particle size can effectively enhance bioavailability. For nanoemulsions, incorporating drugs into the oil phase of oil-in-water (O/W) nanoemulsions results in improved absorption. The presence of nanodroplets increases the contact area between the nanoemulsions and the gastrointestinal mucosa, leading to a significantly higher absorption rate compared to that of conventional emulsions.

Reduced Droplet Re-Agglomeration

The two regions of active homogenization are referred to as the narrow zone and the re-agglomeration zone. In the narrow zone, droplets break apart rapidly with minimal re-agglomeration. Conversely, in the re-agglomeration zone, droplet interactions become more pronounced, leading to a decrease in turbulence intensity. Effective control of droplet size is achieved through a balance between breakup and re-agglomeration, which can be minimized by:

Addition of Emulsifiers/Surfactants - The addition of emulsifiers and surfactants addresses thermodynamic instability by coating newly formed droplets, thereby stabilizing them and preventing coalescence. The choice of emulsifiers or surfactants may vary based on the residence time of the emulsion in the dispersion zone.

Optimizing Energy Input in the Emulsification Process - Within a specific range, droplet size cannot be further reduced, and the efficiency of the emulsifier may also decrease. Excessive processing can result in poor droplet stability.

Dispersed Phase Concentration - An increased concentration of the dispersed phase leads to larger droplet sizes, complicating the droplet breakdown process. Consequently, the effectiveness of the emulsifier in covering newly formed droplets diminishes.

Temperature - The application of thermal homogenization processes increases the velocity of drug particles, thereby enhancing drug distribution and facilitating size reduction. This method is primarily utilized for lipid carriers. However, it also presents certain disadvantages, such as limited applicability for heat-labile substances, potential degradation, and uncertain lipid conversion. Cold homogenization can address these drawbacks. Both methods hold their own significance and can be employed independently or in combination to achieve the desired size reduction.

Improved Drug Loading Capacity and Encapsulation Efficiency

Nanostructured lipid carriers loaded with didanosine were prepared by combining conventional homogenization with both cold and hot homogenization techniques. The drug loading capacity and encapsulation efficiency of the nanostructured lipid carriers loaded with didanosine, produced using a high-pressure homogenizer, were initially very low due to the hydrophilicity of the drug. However, the loading and encapsulation efficiency values for didanosine increased to 3.39 ± 0.63% and 51.58 ± 1.31%, respectively, when employing cold and hot homogenization methods. This improvement indicates that the solubility of didanosine in the lipid phase was significantly enhanced, achieved by reducing its particle size through the hot high-pressure homogenization process.

Reduce the Aggregation of Liposome Vesicles

Small unilamellar liposome vesicles are known to enhance plasma circulation time and achieve improved tissue localization. High-pressure homogenizers are an emerging technology widely utilized to minimize vesicle aggregation, which can decrease the prevalence of multilamellar liposomes. For instance, the albumin-bound paclitaxel drug delivery system employs a high-pressure homogenizer to incorporate albumin and paclitaxel. Furthermore, when preparing vesicular phospholipid gels, the intense pressure conditions of the high-pressure homogenizer are utilized to hydrolyze phospholipids, resulting in the formation of small unilamellar vesicles.

Preparation of Colloidal Formulations

The premixes used for the preparation of nanoparticles with high-pressure homogenizers can consist of coarse emulsions, dispersions, or suspensions. These premixes are created by dispersing a liquid phase (the dispersed phase) into another phase (the dispersion medium) through mechanical shearing or the application of physical energy. For suspensions and dispersions containing larger particle sizes, it is advisable to pre-treat them using high-energy systems such as ultrasound, high-shear homogenizers, or membrane emulsification systems before processing them in the high-pressure homogenizer. This pretreatment is essential, as larger particles may obstruct the gaps within the homogenizer.

In a high-pressure homogenizer, the premix is forced from the inlet chamber to the outlet chamber through a narrow gap under high pressure. The homogenized product can be recirculated into the feeder to continue the homogenization process, allowing for further particle size reduction. The final product is then freeze-dried. The versatility of high-pressure homogenizers has made them more popular than other methods in the development of lipid nanoparticles. Both hot homogenization and cold homogenization have yielded positive results in nanoparticle development.

Conclusion

Formulating nanoparticles with high-pressure homogenizers enables the customization of various physicochemical properties, thereby enhancing the stability, efficacy, and delivery of active pharmaceutical ingredients (APIs).

An added advantage of the high-pressure homogenizer is its ability to utilize two forces: one resulting from mechanical action and the other from pressure, to process particles. This dual action enables the production of consistent and uniform particle sizes. The processing steps of molecular liquids—including impact, cavitation, turbulence, and shear forces—significantly influence the formation of uniformly sized particles and enhance their stability. The outcomes of high-pressure homogenizer processing can impact various therapeutic approaches, including bioavailability and improved targeting capabilities. These factors are crucial for drug delivery systems in nanomedicine, as achieving a small particle size with the appropriate surface area is essential for the effective treatment of diseases. High-pressure homogenizer technology is poised to have a broader impact at both industrial and research levels, benefiting from substantial advancements in the capabilities of high-pressure homogenizers, which will provide greater flexibility and functionality for desired drug applications.

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.