An Overview of NanoCluster Powder Formulation Technology - Pharmaceutical Technology

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An Overview of NanoCluster Powder Formulation Technology
The authors describe a technique designed to yield low-density powders with a tailored particle-size distribution over a broad range of respiratory flow rates.


Pharmaceutical Technology
Volume 10, Issue 34, pp. 72-78


Figure 2: The influence of respiratory flow rate on the Aerodynamic particle-size distribution of the budesonide NanoCluster (Savara Pharmaceuticals, Austin, TX) inhalation powder. The authors used an Andersen cascade impactor at 25 C and 45% relative humidity.
Cascade-impaction studies have repeatedly demonstrated the aerodynamic performance of the NanoCluster technology using various formulations and active pharmaceutical ingredients, including steroids, beta-agonists, antihypertension drugs, antibiotics, and compounds to treat autoimmune diseases (17–21). Figure 2 shows the aerodynamic particle-size distribution results from cascade-impaction tests with a budesonide NanoCluster inhalation powder at different respiratory flow rates. These results demonstrate that the budesonide NanoCluster inhalation powder's aerodynamic performance and deposition is only minimally affected by airflow rate, an important characteristic for pharmaceuticals delivered with passive DPIs. Passive devices rely upon the patient's inhalation rate, which naturally varies from person to person. Consistent aerosol performance independent of inhalation rate is therefore highly desired, particularly for lung-compromised, elderly, and pediatric patients.

Manufacturing


Figure 3: Flow chart of the NanoCluster (Savara Pharmaceuticals, Austin, TX) manufacturing process.
High-performance particle-engineering technologies will not be actualized if they cannot be scaled into robust, repeatable, and cost-effective industrial processes. NanoCluster technology can be scaled up for industrial-quantity production. Unlike other particle technologies that require complex, expensive processing equipment to conduct a multistep manufacturing process, NanoCluster powders typically are produced through simplified manufacturing steps (see Figure 3). Active pharmaceutical ingredient powders are reduced to nanosized particles by well-established and accepted processes such as precipitation or mechanical methods such as media milling. In the postprocessing agglomeration approach shown in Figure 3, the nanoparticles are discharged into a tank to form a quasi-stable colloid before agglomeration. Agglomeration can be accomplished through several methods, including the metered addition of a small amount of an excipient or the simple adjustment of processing parameters. NanoCluster formulations sometimes require little (<5%) or no excipient to achieve the desired product characteristics.

In-processing agglomeration is another approach for controlling agglomeration during the production of NanoCluster particles. With this approach, the nanoparticle creation and agglomeration occur simultaneously, obviating the need to form a nanoparticle suspension. As soon as a small nanoparticle is broken off of a larger particle through attrition, the nanoparticle adheres to another nanoparticle. A significant benefit of this process is that it removes the need for excipients in the final formulation.

After nanoparticles agglomerate into micrometer-sized NanoClusters, operators remove the water used during the process through lyophilization or spray drying to yield low-density, high-performance powders. Further development work is currently underway to determine the technological and financial advantages of each drying method when forming NanoClusters with various active ingredients. Despite their small aerodynamic size, the NanoCluster formulations' physical characteristics make them suitable for downstream handling. Experience to date suggests that relatively few processing steps will be required to manufacture product at commercial scale. Standard powder-handling and -filling techniques suffice for packaging NanoCluster formulations into reservoir-type inhaler devices, capsules, or unit-dose blisters.


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