TECHNOLOGY
OVERVIEW
Historically, the most common route of administration for delivering medications has been orally, which subjects the majority of the dose to liver degradation prior to entering the blood stream. This can be avoided though directly introducing the medication into the blood stream through a needle and syringe but it comes with its own potential complications and drawbacks. Research shows that properly prepared treatments delivered to the deep lung have substantially the same uptake as injectables.
The surface area of the lung alveoli, is equal in size to the surface area of a tennis court, thus making the lungs the human body's largest area of exposure to the outside world. This alveoli network is the perfect mechanism to introduce medication directly into the blood stream without the use of needles.
Deep lung delivery alleviates many of the problems inherent with traditional deliverables. The problems of low bioavailability, inconsistent delivered dose, and storage degradation are remedied by processing the API into dry powder Inhalables and sublingual formulations using KelSie’s proprietary CAN-BD Technology.
GENESIS
This technology was perfected for the delivery of pharmaceutical grade API’s by Dr. Robert Sievers during his successful completion of a $20 Million, 5-year grant funded by the Gates Foundation to develop an inhalable dry powder needleless measles vaccine, which can be self-administered without an experienced caregiver, in precisely measured doses, with a storage life of up to 4 years without electricity or refrigeration. The CAN-BD process produces stable micro-particles suitable for inhalation aerosol or sublingual delivery.
Dr. Robert Sievers is the founder and Chief Scientist of Sievers Biotech and is a nationally recognized authority on Aerosols with over 40 years’ experience as a Professor of Atmospheric Chemistry, researcher, and inventor credited with over 30 patents. Sievers Biotech has entered into a Worldwide Licensing Agreement with KelSie Biotech, LLC for the use of Sievers Biotech’s technology and intellectual property for the commercial development and use of its patented supercritical fluid nebulization and bubble drying process (“CAN-BD”), including, the creation of formulations for sale of finished products.
CAN-BD
Conventionally, spray drying is simply used as a mechanism for drying a certain formulation. The resultant particle morphology is thus entirely determined by the combination of excipients included in the formulation, such as shell-formers and blowing agents, and is not affected by the spray drying process parameters. KelSie’s unique powder formation process provides a long-anticipated additional agent in controlling particle morphology, in conjunction with formulation, for a two-pronged approach. The process creates a homogenous mixture of liquid CO2 and feed solution, providing substantial vaporization energy for the atomization of droplets, and creating a droplet size distribution that is uniform and precisely controllable. The CAN-BD system was specifically engineered to produce particle sizes around three microns, ideal for pulmonary delivery, including nano-scale particles that are ideal for rapid dissolution.
In addition to the production of customizable particle size distributions, our unique, patented Carbon Dioxide- Assisted Nebulization with a Bubble Dryer (CAN-BD®) is also beneficial in its effects on particle morphology.
Upon homogeneous mixing, a fraction of the liquid CO2 becomes dissolved in the feed solution, resulting in a droplet fully saturated with the gas. When the droplet exits the outlet and experiences a lower pressure, the dissolved CO2 exceeds its solubility limit, and escapes the droplet with energetic volatility. Although this desolvation process is energetic, it occurs at a much slower rate and becomes a vital instrument in controlling particle morphology without the use of potentially detrimental blowing agents.
Many pharmaceutical manufacturers produce lyophilize products for reconstitution by healthcare workers as liquids for injection at a later time. Unfortunately, a number of modern products cannot tolerate the stress of lyophilization and must be presented as liquid formulations with attendant risks from stability and access to the cold chain. Offering a technology that is friendly to labile formulations and amenable to long term, stable storage as powders is an important feature of KelSie’s products.
FORMULATION
The CAN-BD process and formulations can be tailored to produce virtually any size particle depending on the desired application and target site. KelSie is capable of consistently creating powder particles ranging in size from 10 nano meters to 20 microns. However, the ideal particle size for respirable delivery is between 1-5 microns (see figure 1 below). whereas larger particle sizes are better suited if powder flowability is an important parameter, as is the case in sublingual tablet delivery.
Figure 1: Scanning electron micrograph of one of KelSie’s inhalable powders composed of hollow, low-density particles & demonstration of dispersibility of powder.