Narrow Particle Size Distribution
ASFD Technology

What is ASFD?

Atmospheric Spray Freeze Drying (ASFD) is an alternative to conventional lyophilization and spray drying methods for improved shelf stability.
  • Faster processing compared to lyophilization (hours not days)
  • Gentler on proteins compared to spray drying (no high heat)
  • Result is a loose, flowing powder, not a cake requiring additional processing
Improved particle properties
  • Aerodynamic for consistent, targeted delivery via the pulmonary or nasal routes
  • High surface area for rapid reconstitution
  • Ideal for self-administration devices
Improved economics and better control of the process
  • No need for the complex vacuum systems of lyophilization
  • Low temperatures means higher viable protein yields compared to spray drying
Ideal for:
  • Protein based pharmaceuticals with poor shelf-stability
  • Pulmonary targets (antibiotics, vaccines, cancer treatments, asthma medications, etc.)
  • Accessing systemic circulation through pulmonary routes (insulin, antibiotics, cancer treatments, etc.)
  • Nasal cavity targets (vaccines)
Applications

Protein Based Pharmaceuticals

Proteins are complex bio-molecules responsible for a great number of functions in the human body.  Each protein has a specific task it must accomplish – signaling, regulation, transcription or structure, for example – and researchers have discovered that many diseases are related to defects in proteins.  For this reason, pharmaceutical companies have greatly expanded their research and development efforts on protein based pharmaceuticals in recent years.

Unfortunately a protein’s complex nature also makes it very fragile, a fact that requires it to be maintained in precise conditions to ensure its activity.  While freezing proteins in solution has been used, it is a costly proposition considering the many financial and logistical drawbacks of cold-chain storage.  A better alternative is to convert pharmaceuticals into a dry powder, where room temperature shelf stability can be maintained for years.  Traditional dry powder manufacturing methodologies, including lyophilization and spray drying, can be damaging to the proteins they are trying to protect.  ASFD is a gentler process and allows for greater flexibility during formulation.

Targeted and Systemic Delivery

Most traditional medicines are given orally, topically or by injection.  While dry powders can be used in these applications, they also can be inhaled into the lungs for targeted or systemic delivery. 

There are a vast number of targeted applications including the delivery of anti-inflammatory agents to the constricted airways of asthmatics, vaccines for the prevention of disease, or antibiotics to the site of infection in patients with pneumonia.  In all these cases the use of dry powders offer significant advantages compared to traditional medicine because the targeted delivery can lead to dose sparing and minimization of side-effects. 

The human lungs have a surface area roughly equal to that of a tennis court to aid in the exchange of oxygen and carbon dioxide gas to and from the blood.  This fact, combined with the incredible perfusion of each alveolus, make the lungs an ideal location for the delivery of drugs whose target is the systemic circulation.  In addition, first pass elimination is avoided, potentially leading to dose minimization and a reduction in toxicity and side-effects.

The traditional dry powder manufacturing methods of lyophilization and spray drying do not produce particles with consistent aerodynamic properties amenable for targeted or systemic delivery.  With ASFD, engineered particles with consistent spherical shape and size mean more of the drug gets to its intended delivery location.  The ASFD particles also have high surface areas that allow them to dissolve fast before the body’s clearance mechanisms clear them from the system.

Self-Administration

The escalating cost of healthcare is driving a revolution in medicine.  More and more the patient is being asked to take an active role in their own health solution, including the delivery of pharmaceuticals.  Self-administration devices are empowering patients to take medicines that were once only available if administer by a trained healthcare worker.  Whether by inhalation, intranasal administration or reconstitution micro-infusion, self-administration devices are going to be a significant part of the drug delivery landscape.  ASFD particles are engineered specifically to meet the needs of the self-administration market and the next generation of self-administration devices.

Delivery Methods

Pulmonary Delivery

Pulmonary administration is an important delivery route for a wide range of medications because of the ability to access the vast surface area of the lung or target specific locations along the way.  It also enables self-administration needed for lower healthcare costs now and in the future.

ASFD powders are ideal for pulmonary delivery because of important engineered properties.  They have a spherical shape giving them good aerodynamic stability as they traverse the pulmonary tract from mouth to alveolus.  Whether the target is the upper respiratory tract for an asthma medication or the deep lung for absorption into the systemic circulation, ASFD powders can be manufactured in a wide range of particle sizes, each with a tightly controlled distribution.  Because of their high porosity, ASFD powders dissolve rapidly once they reach their target, leaving little time for the body’s ciliary clearance mechanisms to reduce their effectiveness.

eBio’s scientists and engineers are experts in pulmonary delivery and can help design your pharmaceutical for maximum effectiveness.

Nasal Delivery

The nasal cavity is the location of many important immunologic defense mechanisms, making it an ideal candidate for vaccine delivery.  ASFD powders are well suited for nasal delivery because of the ability to tightly control particle sizes.  Particles that are too small can be inhaled into the lungs or land in the upper cavity and the olfactory bulb.  Particles that are too large can cause irritation or induce sneezing. 

Let eBio’s scientists and engineers help direct you toward the optimal design.

Nano

Because of the flexibility provided by ASFD processing, particles in almost any size range can be manufactured.  Current atomization technologies enable particles to be manufactured that are smaller than 1 micron, including particles as small as 100 nanometers.  Though applications are still in the development phase for particles this small, Engineered BioPharmaceuticals is preparing to meet the needs of these exacting requirements.  In medicine today, however, there is a need to deliver nano-sized molecules in both targeted and systemic delivery modes.  ASFD particles are ideal for the seamless integration and delivery of nano-molecules.

Reconstitution

One of the largest applications currently for dry powders is in the reconstituted delivery of medicines.  Here, dry powders are mixed with water-for-injection just prior to patient administration.  ASFD particles greatly aid in this delivery method as their high surface area greatly reduces reconstitution time, enabling next generation, one-step devices (i.e. devices that reconstitute automatically during injection).  Engineered BioPharmaceuticals is currently constructing a plant for the aseptic production of ASFD powders, something required for reconstituted pharmaceuticals.  When completed this line will not only produce powders but also fill them into a closed container – all under an aseptic umbrella.

Why it Matters

The past few years have witnessed the beginnings of a revolution in healthcare.  Cognizant of the ever increasing cost of healthcare, able governments worldwide have enacted legislation aimed at helping their citizens find medical coverage at reasonable costs.  Unfortunately, without measures to control the continuously escalating expense of diagnosis and treatment, they also may soon find themselves fighting a spiraling deficit with no apparent ceiling and the concomitant need to ration service.  The only reasonable solution is to lower the overall cost of healthcare, currently estimated at more than $2.2 trillion in the US, by improving efficiency and removing waste.

In contrast to this struggle are the very exciting discoveries and advancements being made daily through genomics research.  Envisioned when the human genome project began, disease treatment options are rapidly expanding as small molecule drugs are being sidelined in favor of target specific protein based pharmaceuticals.  The burgeoning field of proteomics carries with it the hope and promise to cure many diseases, but also the increased cost inherent in any new technology.  Here, at this intersection, is a grand challenge:  continue to advance the state-of-the-art in medicine but ensure all Americans have access.  Engineered BioPharmaceuticals (eBio) was formed to take on this challenge.

eBio’s focus:
  1. Pharmaceutical manufacturing
  • Convert liquid based pharmaceuticals to “engineered” dry powders for pharmaceutical and biotech partners
  • Key dry powder process:  Atmospheric Spray Freeze Drying
  • Fill and finish the dry powders into appropriate delivery devices
  • Perform all pharmaceutical manufacturing in an aseptic environment
  1. Proprietary pharmaceutical development
  • Nano-carrier for drug delivery
  • Inhalable antibiotic
  • Improved asthma treatment
  1. Diagnostic
  • DNA protection for tissue sampling
  • Non-invasive disease detection
Medical Benefits

The ASFD process produces particles with properties that are superior to conventional drying methods.  Highly uniform particles with improved aerodynamics allow consistent, targeted delivery via pulmonary and nasal routes.

Commercial Benefits

Atmospheric spray-freeze-drying is much more economical than lyophilization or spray-drying processes.  With ASFD, there are no high vacuum or heating requirements and the particle production methods are easily scalable. Unlike lyophilization, ASFD is a fairly quick procedure, taking only hours to produce particles as opposed to days. This process is also very easy to monitor and provides better control of particle size and morphology.

Social Benefits

The ability of ASFD particles to reach only their targeted location will help minimize side effects of drugs. This will allow drugs that have been shelved because of undesirable side effects to be brought back into production, eliminating the need and cost of creating entirely new drugs to treat the same aliment. Another benefit of the ASFD process is the ability to deliver protein based drugs in new, novel self-administration modalities, such as inhalation and self-reconstituted micro injectors. Eliminating the inconvenience and expense of requiring healthcare worker administration of drugs will have a positive effect on patient therapeutic compliance. The global benefit of ASFD is that it extends the shelve-lives of drugs, enhances their mass distribution and allows drugs to be self-administered. This will lead to successful mass-immunization campaigns and help minimize large-scale effects of pandemics or bio-terror threats.


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