Aerosol Generation

Aerosol Drug Delivery

Aerosol Delivery of Biotherapeutics

Inhalation Toxicology



SUPRAER is a new class of aerosol drug generation and delivery system that provides pharmaceutical companies new options for high dose-rate aerosol drug delivery.

SUPRAER™ is a versatile aerosol generation system that can be used to generate fine particle aerosols from aqueous formulation. When used without a concentrator it can be used to generate nanoparticles and non-flammable vapors. It has the capability for the generation, collection, delivery and sampling of aerosols.

Key technologies are included in SUPRAER:

Aerosol Generation Technology

KAER specializes in single-pass aerosol generation nozzle technology. Single pass means that 100 % of the fluid entering the nozzle is aerosolized. There is no recirculation. To avoid shear induced degradation of biotherapeutics, KEAR uses nozzles with low shear stresses to produce the particles. Thus, any molecular or functional acitivity of the aerosolized agent is maintained. KAER uses several proprietary nozzle technologies. These include low shear nozzles (KB-N-) that use both high pressure air and high pressure fluid. These nozzles can be tailored to give the desired particle size. They can deliver both relatively narrow size distributions or near monodisperse aerosols. In addition we have nozzles that operate at low pressures and do not require the pressurization of the fluid. These nozzles also enable precise metering of the dose delivered. This technology is suitable for nasal aerosol delivery as well as the aerosolization of labile biologics, microorganisms and cells.


Nozzle KB-N-700, compressed air pressure 60 psi, fluid flow rate 3 ml/min

Aerosol Conditioning Technology

KAER's aerosol processing system is ideal for generating and processing of aerosols under constant conditions of flow rate, humidity and temperature. This system can be used to generate, dilute and evaporate aerosols under highly controlled conditions. Thus, providing a multipurpose system for the generation of nano particles, fine particle aerosols and vapors.

Aerosol Concentration Technology

Low flow and high flow concentrators are available. The high flow compact virtual impactor aerosol concentration technology weighs just 100 gram yet can process 200 l/min and provide a concentrated aerosol output. Alternatively, this concentrator can be used to concentrate high volumes of environmental airborne particles for collection on a small filter. The low flow concentrator is ideal for the delivery of high concentatios of aerosols to small animals. In addition, these concentrators can be used in series to obtain even aerosol concentrations over 15 mg/l.




High flow concentrator





Low flow concentrator



Technical Operation of SUPRAER

SUPRAER generates a large aqueous aerosol of the active agent that is rapidly dried, concentrated, and delivered on demand as a solid phase respirable aerosol of pure agent.  It does this through the use of proprietary low shear nozzles in combination with an innovative particle drying chamber and low resistance particle concentrator(s).  In concert, these technologies enable the generation of high concentrations of particles on-the-fly for use in a clinical aerosol delivery system.  Thus SUPRAER is in a class by itself in overcoming the shortcomings of current aerosol technology in delivering high doses of large labile molecules.


schematic function




Schematic showing the functional features of SUPRAER






Diagramatic operation of SUPRAER



Diagramatic representation of the generation, evaporation, concentration and delivery of aerosols by SUPRAER







SUPRAER for Laboratory Use (SUPRAER-CA)






(High flow concentrator)









(Low flow concentrator)




The current models for laboratory use, SUPRAER-CA (air provided by a compressor) is suitable for bench studies and animal testing. These devices allow control of the operating parameters regulating the aerosol processing and thus particle size, morphology and delivery rate.

It could also be used for initial human investigational studies. Visually simplified and stylized versions of each are planned for hospitals and clinics.

Principles of Operation

Generation of the Aerosol
Within the nozzle, the fluid flows through a centrally located capillary such that the aerosol exits the aerosol exit orifice without interacting with the orifice surface.  The size of the initial particles can be tailored depending on the application. Geometric standard deviations are typically between 1.6 and 2. These liquid particles shrink in size when the liquid is evaporated. The generation of large liquid particles requires much less energy than the generation of smaller particles from the same mass of fluid.  This minimizes any shear-induced degradation of the molecules dissolved or suspended in the fluid for aerosolization.  SUPRAER contains no baffles for jet impaction and secondary particle formation.  Such baffles have been shown to cause shear degradation of large molecules. Also, as large liquid particles are generated SUPRAER extends the range of solution viscosities (up to 40 cSt) that can be successfully aerosolized to produce inhalable aerosols.

As noted, the liquid aerosol is evaporated to form an aerosol of dry solid phase particles. The manner in which this drying occurs can affect the physical characteristics of the dry particles.  Thus controls are incorporated in SUPRAER to provide considerable flexibility in the control of the drying process. This optimizes the potential for generating respirable particles with the desired characteristics.  The characteristics of the resulting particles are governed by the physicochemical properties of the molecules or mixture of molecules contained within the fluid, the physicochemical properties of the fluid, as well as their concentrations.   

Dilution of the Aerosol
SUPRAER integrates several features to augment the evaporation of the fluid from the aerosol in the evaporation chamber.

  1. Augmentation of the dilution of the aerosol jet.  A localized counter-flow jet of gas is directed directly into the aerosol plume near its base. This plume is arrested midway between the jet and the counter-flow tube, which both disperses the aerosol plume and enables the device to be extremely compact.  The pressure and flow of the nozzle and counter-flow are metered. The compressed air pressure is adjustable up to 60psi.
  2. The dilution air transports the aerosol through the evaporation chamber.  The arrested plume is diluted by warm gas, (typically 150-200 liters per minute when the high flow concentrator is used).  This gas flow dilutes and transports the aerosol through the evaporating chamber. The dilution airflow rate is metered and is continuously adjustable up to 200 l/min.

Energy to supply the latent heat of evaporation

  1. Heating the compressed gas to the nozzle and the counter-flow tube.  Provision of this thermal energy and dilution locally within the plume enables the fluid to rapidly evaporate as close to the source of formation as practical.  Thus, although this gas may be quite warm, the aerosol particles are cooled by the latent heat of evaporation. The temperature of the compressed air can be set on its PID controller.
  2. Heating the dilution air:  The temperature of the dilution air can be set on its PID controller.
  3. Provision of infrared heating: Water has a very strong infrared absorption band.  Thus, an infrared lamp optimized for emission in this absorption band is incorporated into the console. Cylindrical aluminum reflectors focus this infrared emission into the quartz evaporation chamber. The infrared radiation is continuously variable.  A quartz evaporation tube is used as the infrared radiation is readily transmitted though it.

The operator can choose to incorporate each or any of these heaters to control the energy delivered to the aerosol.

Concentration of the aerosol
The dried aerosol from the evaporation chamber enters the aerosol concentrator.  The concentrator works on the principle of virtual impaction.  In the high flow concentrator, aerosol is accelerated as it passes through a radially arranged set of slit acceleration nozzles.   The aerosol particles have a high momentum as compared to the gas molecules in which they are suspended.  Thus, the aerosol particles propelled by their momentum enter a set of corresponding radially arranged deceleration slit nozzles positioned just a short distance from the acceleration nozzles.  As the inhalable output aerosol flow is generally restrained to about 1/8 of the flow through the evaporation chamber, some 7/8 of the gas exits the aerosol stream through the gap between the acceleration nozzles and the deceleration slit nozzles.  The concentrator has an exhaust plenum and filter to collect and remove any particles which are contained within the exhaust air.

Output aerosol
The concentrated aerosol is further decelerated at the output of the concentrator and directed through an aerodynamically engineered output cone.   This output aerosol is provided at a slight positive pressure (1-2 inches of water).  Attaching a flow-limiting device to the output cone will regulate the output to the desired flow rate.  This device could be a valve, filter, animal inhalation system or any other appropriate system requiring this aerosol input.

Control of particle size


a) Concentration of solute or suspension
The size of the residual particles is primarily dependent on the concentration of the dissolved or suspended solute or colloid in the fluid for aerosolization.  For example, doubling the geometric particle size requires 8 times the concentration of solute or colloid. 

b) Regulation of the physical density and morphology of the particles
Large particles with much smaller aerodynamic diameters can be produced.  This requires some expertise choosing the physicochemical properties in the formulation and the judicious choice of particle drying parameters. 

c) The desired particle size can be generated through changing the components and settings for SUPRAER

1. Determine the drug formulation's concentration and the corresponding fluid flow rate that will give the desired aerosol dose rate;

2. Determine which nozzle will generate an aerosol of the desired primary particle size according to the pre-determined drug formulation's concentration and fluid flow rate;

3. Determine the optimum compressed gas pressure that will further modify the particle size as needed;

4. Determine which concentrator or combination of concentrators will provide the desired dose concentration at the flow rate desired.

Note:  The concentrator is designed to concentrate particles with an aerodynamic diameter greater than 1 micron mass median aerodynamic diamter, MMAD.  The efficiency of the concentrators are particle size and flow rate dependent up to about 85%. When dilute solutions are used to produce small particles, the efficiency of the concentrator will be reduced accordingly.

Key features of SUPRAER include:

  • Single-pass nozzles
    • Large aerosol exit orifice (500-700 μm diameter)
    • Extends the viscosity (>40 cP), and thus molecular weight, and concentration range deliverable via aerosol delivery
    • Generates liquid aerosols at rates from 50 μl to 3 ml/min
    • Aerosolizes 100% of fluid input
    • Enables aerosolization of surface-active agents
    • Aerosol exits the nozzle in the center of a gas sheath
    • Eliminates dripping and clogging of the nozzle during high dose delivery
    • Initial particle size is relatively large minimizing any shear degradation
    • No secondary impaction stage is necessary minimizing losses and shear degradation
  • Delivers solid phase surfactant/protein aerosols of pure drug
  • Delivers preselected size (2-4 μm MMAD) with narrow size distribution (sg, 1.6-2)
  • Delivers dose-rates up to 4 mg/s
  • Delivers up to ~2 g in 10 minutes.
  • Aerosol delivery “on demand”
  • Provides a positive pressure respiratory assist
  • Delivers aerosol with absolute humidity of 5-15 mg/l (hospital environment humidity 4- 10 mg/l)
  • Assembly and cleaning – 5 user serviceable parts; all are easy to clean. 
  • There are no wet surfaces
  • Reproducibility is very high, SD<5%
  • No additional excipients required
  • Surfactants low surface tension is retained following resuspension of solid phase aerosol output
  • Particles with low density may result thus decreasing the aerodynamic diameter
  • Each dry particle contains 25 times the mass of surfactant than a similar sized aqueous aerosol generated from a 2-4% surfactant suspension
  • Minimizes any agglomeration
  • No additional fluid load to the patient
  • Molecular and functional integrity of biologics are maintained
  • Uses proprietary replaceable multiuse nozzles and nozzle holders

Benefits from adopting SUPRAER as your drug delivery platform

  • SUPRAER systems and methods patents have been issued in the US and EU, Japan, and China with further appications pendiing in all these countries as well as India. This provides the potential for further Intellectual property protection of your API with a new delivery system.

  • No excipients are required, resulting in savings in formulation development time and additional safety testing costs. This is beneficial for companies pursuing life cycle extensions through a switch from IV to inhalation delivery with either new biological agents or existing agents.

  • The agent is delivered directly to the site of action for diseases of the lungs.  A reduction in dose of biotherapeutics of up to 80% can result when changing from IV to inhalation delivery.

This provides major decreases in:

  • Cost of goods for pharmaceutical companies
  • Potential systemic side effects compared to higher IV dosages
  • Treatment time required

The range of agents that benefit from administration with SUPRAER includes:

  • Biotherapeutics, such as proteins, fusion proteins, peptides, antibodies, antibody drug conjugates, surfactants, oligonucleotides, liposomes as well as microorganisms .

  • Anti-infectives including antibiotics, antifungals and antiprotozoals

  • Anti-cancer agents, such as doxorubicin, paclitaxel, and drug conjugated antibodies.

  • Anti-asthma/COPD agents, such as corticosteroids, antibodies and mucokinetics

  • Systemic therapies, where the large surface area of the lung facilitates ready access to the systemic circulation.

Thus, SUPRAER has clear competitive advantages over other aerosol delivery systems available when delivering large masses of active agents to the respiratory tract.


Future SUPRAER versions

Once the ideal and specific operating parameters of the treatment-specific biotherapeutic have been defined using the laboratory version, further simplified SUPRAER versions with all parameters fixed are envisioned for clinical use and home use. Visual inhalation and dose delivered status parameters are incorporated into these units to provide feedback to the patient.




Small Animal Respiratory Exposure System (SARES™)

KAER has developed and manufactured a Small Animal Respiratory Exposure System (SARES) to use with SUPRAER. This unit has been optimized to take advantage of the high biotherapeutic dose rates provided by SUPRAER.  Additional value to partnerships is provided by KAER’s capability to conduct the required small animal inhalation efficacy and toxicology studies with this unit using SUPRAER.


Key Applications for SUPRAER

  • A drug delivery system for

    • High dose aerosol inhalation of proteins, peptides, surfactants, oligonucleotides, antibodies, liposomes, anti-infectious agents and chemotherapeutics
    • Hospital, clinic or home use
    • Use In combination with SARES - ideal for exploratory or high dose animal inhalation exposure safety or toxicology studies required by the FDA, OSHA, EPA, or the Dept. of Defense.
  • A miniature spray drier for creating dry particles of proteins, peptides, surfactants, oligonucleotides, antibodies, plasmids, anti-infectious agents, chemotherapeutics, vaccines and liposomes.


  1. Yeates, DB. High Dose rate generation of fine particle aerosols of antibodies with SUPRAER® compared to two mesh nebulizers.  Respiratory Drug Delivery 313-316, 2013.
  2. Yeates, DB, Heng, X, Targeting the optimal particles size and output for aerosol drug delivery using SUPRAER®.  Respiratory Drug Delivery 395-400, 2016.
  3. Yeates DB, and Heng X. Generation of respirable particles from surfactant suspensions and viscous solutions at high Dose Rates. Drug Delivery to the Lungs 27 205-208, 2016.
  4. Yeates DB, and Heng X. Augmentation of the generation, processing and delivery of surfactant and macromolecule aerosols with heliox. J Aerosol Med Pulm Drug Deliv. 30(3), 2017


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