Preservation by vaporization
First Claim
1. A method for preserving one or more therapeutically active biologicals, comprising:
- partially freezing a suspension comprising;
one or more therapeutically active biologicals;
one or more protective excipients; and
an aqueous solutionby cooling to a temperature above −
20°
C. to obtain a slush comprising a mixture of ice crystals and a liquid between the ice crystals;
performing primary drying of the slush under conditions to prevent or inhibit splattering of the liquid to provide a mechanically stable foam optionally comprising a skim of a thin freeze-dried cake;
wherein the conditions comprise applying temperatures above −
20°
C. and a vacuum pressure below 3 Torr so the liquid boils and the ice crystals sublime; and
performing secondary drying by desorbing water from the mechanically stable foam under high vacuum at ambient temperature or above to increase the foam'"'"'s glass transition temperature to provide preserved therapeutically active biologicals in a glassy matrix that is stable at ambient temperatures; and
wherein the biologicals are not subjected to temperatures equal to Tg′
or below, wherein Tg′
is the temperature at which the suspension completely solidifies during cooling.
1 Assignment
0 Petitions
Accused Products
Abstract
Significant research is being done to develop and improve delivery mechanisms for biopharmaceuticals and vaccines, including pulmonary (inhalation), nasal, transdermal, and oral alternatives. Market projections indicate that the delivery of proteins and vaccines by inhalation and oral formulation has become and will continue to be increasingly important. These delivery mechanisms, to be effective, will require better stabilization of the biologicals so that they can maintain potency and effectiveness at ambient temperatures for extended periods of time. The novel Preservation by Vaporization (PBV) Technology described herein provides cost-effective and efficient industrial scale stabilization of proteins, viruses, bacteria, and other sensitive biologicals, thereby allowing a production of products that are not possible to be produced by existing methods. The suggested new PBV process comprises primary drying under vacuum from a partially frozen state (i.e. slush) at near subzero temperatures followed by stability drying at elevated temperatures (i.e., above 40 degrees Celsius). The new suggested method can be performed aseptically in unit doze format (in vials) and/or in bulk format (in trays, bags, or other containers). The drying can be performed as a continuous load process in a manifold vacuum dryer comprising a plurality (e.g., 30) of vacuum chambers attached to a condenser during the drying.
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Citations
25 Claims
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1. A method for preserving one or more therapeutically active biologicals, comprising:
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partially freezing a suspension comprising; one or more therapeutically active biologicals; one or more protective excipients; and an aqueous solution by cooling to a temperature above −
20°
C. to obtain a slush comprising a mixture of ice crystals and a liquid between the ice crystals;performing primary drying of the slush under conditions to prevent or inhibit splattering of the liquid to provide a mechanically stable foam optionally comprising a skim of a thin freeze-dried cake; wherein the conditions comprise applying temperatures above −
20°
C. and a vacuum pressure below 3 Torr so the liquid boils and the ice crystals sublime; andperforming secondary drying by desorbing water from the mechanically stable foam under high vacuum at ambient temperature or above to increase the foam'"'"'s glass transition temperature to provide preserved therapeutically active biologicals in a glassy matrix that is stable at ambient temperatures; and wherein the biologicals are not subjected to temperatures equal to Tg′
or below, wherein Tg′
is the temperature at which the suspension completely solidifies during cooling. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A scalable method for preserving one or more therapeutically active biologicals, comprising:
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partially freezing a suspension comprising; one or more therapeutically active biologicals; one or more protective excipients; and an aqueous solution by cooling to a temperature higher than −
20°
C. to obtain a slush comprising a mixture of ice crystals and liquid between the crystals;performing primary drying of the slush under conditions to prevent or inhibit splattering of the liquid to provide a mechanically stable foam; wherein the conditions comprise applying a temperature above −
20°
C. and a vacuum pressure below 3 Torr so the liquid boils and the ice crystals sublime; andperforming secondary drying of the mechanically stable foam under high vacuum at ambient temperature; and continuing the secondary drying at temperatures greater than 40°
C. to provide preserved therapeutically active biologicals in a glassy matrix that is stable at ambient temperatures for long term storage; andwherein the biologicals are not subjected to temperatures equal to Tg′
or below, wherein Tg′
is the temperature at which the suspension completely solidifies during cooling. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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Specification