We have successfully demonstrated the formulation of a wide range of thermostable biologics.
We have demonstrated long-term ambient temperature stability (including at 37°C, and higher temperatures) for extended periods of time for live attenuated viral and bacterial vaccines in dry state.
Live viral vaccines - Small pox, Yellow Fever, Measles, Rubella, Rabies, RSV, Influenza
Bacterial vaccines - Shigella, Salmonella, Cholera, Listeria, Sterne Strain Anthrax
We have demonstrated a shelf life measured in years and elevated ambient temperature stability at 37°C and higher for gram positive and gram negative bacteria, including but not limited to:
L. acidophilus, L. rhamnosus, L. reuteri, L. jensenii, L. crispatus, B. lactis, E.coli and other celluar entities stable at high ambient temperatures in dry state.
We have also demonstrated thermostabilty in enzymes, growth factors, therapeutic proteins, and other molecular items at 40°C and higher temperatures in dry powdered form, suitable for oral, nasal, inhalation, and other delivery routes.
Our approach to the stabilization of biologicals in the dry state at ambient temperatures is based on the following facts and working hypotheses:
Effective long-term preservation of biologicals at ambient temperatures (AT) requires immobilization of intracellular macromolecules (proteins, DNA, RNA, etc.) as well as cellular membranes in dry carbohydrate glass below its glass transition temperature Tg. The glass transition temperature is the temperature at which the solution transitions from liquid to glass or from mobile to fixed.
Dehydration may not be a direct damaging factor to biological structure and function. Some of the dehydration-induced damage to unprotected biologicals is associated with hydration forces that rise between biological membranes and macromolecules when the distance between them becomes very small. This dehydration-induced damage can be diminished by replacing a portion of the water of hydration before drying with protective carbohydrates (fillers) that replace the water and adsorb to the surface of the biological membranes and macromolecules. The fillers protect in two ways: they eliminate hydration forces and they also create glassy shells around the biological membranes or macromolecules. Thus, some minimum amount of intracellular filler should be delivered to or present in cells to insure cell survival during drying and subsequent storage at AT.
Dr. Bronshtein was the first scientist to demonstrate (Bronshtein and Leopold 1996) that in order to achieve stability of biologicals (proteins), when stored at room or higher temperatures, the concentration of sugars has to be significantly higher than that required to achieve stability at 0°C.
To preserve biologicals at ambient temperature, one must use protective fillers (for example sugars and amino acids) with high Tg (e.g., above room temperature) in the anhydrous state. Fillers also should not belong to highly reactive chemicals
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