Microscale lyophilization and drying methods for the stabilization of molecules
First Claim
1. A method of obtaining a quantity of a dry, solid form of an agent of interest comprising:
- (a) providing a liquid which comprises an agent of interest dissolved or dispersed in a volatile liquid medium;
(b) depositing a microquantity of the liquid at a preselected site of a substrate; and
(c) drying the microquantity of the liquid by volatilizing the volatile liquid medium to produce a dry, solid form of the agent of interest,wherein the volatile liquid medium comprises an aprotic, hydrophobic, non-polar liquid which comprises biocompatible perhalohydrocarbons or unsubstituted saturated hydrocarbons.
3 Assignments
0 Petitions
Accused Products
Abstract
Methods and systems are provided for microscale lyophilization or microscale drying of agents of interest, such as pharmaceutical agents or other molecules that are unstable or easily degraded in solution. The drying method includes (a) providing a liquid comprising an agent of interest dissolved or dispersed in a volatile liquid medium; (b) depositing a microquantity (between 1 nL and 10 μL) of the liquid onto a preselected site of a substrate; and then (c) drying the microquantity by volatilizing the volatile liquid medium to produce a dry, solid form of the agent of interest. The lyophilization method includes freezing the microquantity of liquid after step (b) and before step (c). By processing the agent of interest in microquantities in controlled contact with a substrate surface, improved heat and mass transfer is provided, yielding better process control over drying of the agent of interest compared to conventional bulk drying or lyophilization.
40 Citations
40 Claims
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1. A method of obtaining a quantity of a dry, solid form of an agent of interest comprising:
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(a) providing a liquid which comprises an agent of interest dissolved or dispersed in a volatile liquid medium; (b) depositing a microquantity of the liquid at a preselected site of a substrate; and (c) drying the microquantity of the liquid by volatilizing the volatile liquid medium to produce a dry, solid form of the agent of interest, wherein the volatile liquid medium comprises an aprotic, hydrophobic, non-polar liquid which comprises biocompatible perhalohydrocarbons or unsubstituted saturated hydrocarbons. - View Dependent Claims (9)
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2. A method of obtaining a quantity of a dry, solid form of an agent of interest comprising:
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(a) providing a liquid which comprises an agent of interest dissolved or dispersed in a volatile liquid medium; (b) depositing a microquantity of the liquid at a preselected site of a substrate; and (c) drying the microquantity of the liquid by volatilizing the volatile liquid medium to produce a dry, solid form of the agent of interest, wherein the volatile liquid medium comprises one or more excipients, which comprise a surfactant. - View Dependent Claims (3, 4)
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5. A method of obtaining a quantity of a dry, solid form of an agent of interest comprising:
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(a) providing a liquid which comprises an agent of interest dissolved or dispersed in a volatile liquid medium; (b) depositing a microquantity of the liquid at a preselected site of a substrate; and (c) drying the microquantity of the liquid by volatilizing the volatile liquid medium to produce a dry, solid form of the agent of interest, wherein the microquantity of the liquid has a volume between 10 nL and 500 nL, and wherein the agent of interest comprises an amino acid, a peptide, or a protein. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17)
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6. A method of obtaining a quantity of a dry, solid form of an agent of interest comprising:
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(a) providing a liquid which comprises an agent of interest dissolved or dispersed in a volatile liquid medium; (b) depositing a microquantity of the liquid at a preselected site of a substrate; and (c) drying the microquantity of the liquid by volatilizing the volatile liquid medium to produce a dry, solid form of the agent of interest, wherein the microquantity of the liquid is frozen after the deposition of step (b) and before the drying of step (c). - View Dependent Claims (7, 18, 19, 20, 21, 22, 23, 24, 25, 26)
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8. A method of obtaining a quantity of a dry, solid form of an agent of interest comprising:
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(a) providing a liquid which comprises an agent of interest dissolved or dispersed in a volatile liquid medium; (b) depositing a microquantity of the liquid at a preselected site of a substrate; and (c) drying the microquantity of the liquid by volatilizing the volatile liquid medium to produce a dry, solid form of the agent of interest, wherein the drying of step (c) comprises subjecting the microquantity of the liquid to a sub-atmospheric pressure. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33, 34, 35)
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10. A method of obtaining a quantity of a dry, solid form of an agent of interest comprising:
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(a) providing a liquid which comprises an agent of interest dissolved or dispersed in a volatile liquid medium; (b) depositing two or more discrete microquantities of the liquid at two or more discrete preselected sites of at least one substrate; (c) drying the discrete microquantities of the liquid by volatilizing the volatile liquid medium to produce two or more microquantities of the dry, solid form of the agent of interest; and (d) combining together the two or more microquantities of the dry, solid form of the agent of interest to form a single collection of the dry, solid form of the agent of interest, wherein the agent of interest comprises insulin.
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36. A method comprising:
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(a) providing a liquid which comprises a pharmaceutical agent dissolved or dispersed in a volatile liquid medium; (b) depositing two or more discrete microquantities of the liquid into two or more respective, discrete microreservoirs located in a medical stent; and (c) drying the two or more microquantities of the liquid by volatilizing the volatile liquid medium to produce dry, solid forms of the pharmaceutical agent in the microreservoirs of the medical stent. - View Dependent Claims (37, 38, 39, 40)
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Specification