High-throughput formation, identification, and analysis of diverse solid-forms
First Claim
1. An array of samples comprising a plurality of solid-forms of a single compound-of-interest, each sample comprising the compound-of-interest, wherein said compound-of-interest is a small molecule, and at least two samples comprise solid-forms of the compound-of-interest each of the two solid-forms having a different physical state from the other.
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Abstract
The invention concerns arrays of solid-forms of substances, such as compounds and rapid-screening methods therefor to identify solid-forms, particularly of pharmaceuticals, with enhanced properties. Such properties include improved bioavailability, solubility, stability, delivery, and processing and manufacturing characteristics. The invention relates to a practical and cost-effective method to rapidly screen hundreds to thousands of samples in parallel. The invention further provides methods for determining the conditions and/or ranges of conditions required to produce crystals with desired compositions, particle sizes, habits, or polymorphic forms. In a further aspect, the invention provides high-throughput methods to identify sets of conditions and/or combinations of components compatible with particular solid-forms, for example, conditions and/or components that are compatible with advantageous polymorphs of a particular pharmaceutical.
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Citations
169 Claims
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1. An array of samples comprising a plurality of solid-forms of a single compound-of-interest, each sample comprising the compound-of-interest, wherein said compound-of-interest is a small molecule, and at least two samples comprise solid-forms of the compound-of-interest each of the two solid-forms having a different physical state from the other.
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2. An array comprising at least 24 samples each sample comprising a compound-of-interest and at least one component, wherein:
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(a) an amount of the compound-of-interest in each sample is less than about 1 gram; and
(b) at least one of the samples comprises a solid-form of the compound-of-interest. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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22. A method of preparing an array of multiple solid-forms of a compound-of-interest comprising:
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(a) preparing at least 24 samples each sample comprising the compound-of-interest and at least one component, wherein an amount of the compound-of-interest in each sample is less than about 1 gram; and
(b) processing at least 24 of the samples to generate and array comprising at least two solid-forms of the compound-of-interest. - View Dependent Claims (23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38)
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39. A method of screening a plurality of solid-forms of a compound-of-interest, comprising:
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(a) preparing at least 24 samples each sample comprising the compound-of-interest and one or more components, wherein an amount of the compound-of-interest in each sample is less than about 1 gram;
(b) processing at least 24 of the samples to generate an array wherein at least two of the processed samples comprise a solid-form of the compound-of-interest; and
(c) analyzing the processed samples to detect at least one solid-form. - View Dependent Claims (40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59)
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60. A method of identifying optimal solid-forms of a compound-of-interest, comprising:
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(a) selecting at least one solid-form of the compound-of-interest present in an array comprising at least 24 samples each sample comprising the compound-of-interest and at least one component, wherein an amount of the compound-of-interest in each sample is less than about 1 gram; and
(b) analyzing the solid-form. - View Dependent Claims (61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85)
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86. A method to determine sets of conditions and/or components to produce particular solid-forms of a compound-of-interest, comprising:
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(a) preparing at least 24 samples each sample comprising the compound-of-interest and one or more components, wherein an amount of the compound-of-interest in each sample is less than about 1 gram;
(b) processing at least 24 of the samples to generate an array wherein at least one of the processed samples comprises a solid-form of the compound-of-interest; and
(c) selecting samples having the solid-forms in order to identify the sets of conditions and/or components. - View Dependent Claims (87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103)
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104. A method of screening conditions and/or components for compatibility with one or more selected solid-forms of a compound-of-interest, comprising:
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(a) preparing at least 24 samples each sample comprising the compound-of-interest in solid or dissolved form and one or more components, wherein an amount of the compound-of-interest in each sample is less than about 1 gram;
(b) processing at least 24 of the samples to generate an array of said selected solid-forms; and
(c) analyzing the array. - View Dependent Claims (105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117)
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118. A system to identify optimal solid-forms of a compound-of-interest, comprising:
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(a) an automated distribution mechanism effective to prepare at least 24 samples, each sample comprising the compound-of-interest and one or more components, wherein an amount of the compound-of-interest in each sample is less than about 1 gram;
(b) an system effective to process the samples to generate an array comprising at least one solid-form of the compound-of-interest; and
(c) a detector to detect the solid-form. - View Dependent Claims (119, 120, 121, 122, 123, 124, 125, 126, 127)
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128. A method to determine a set or processing parameters and/or components to inhibit the formation of a solid-form of a compound-of-interest, comprising:
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(a) preparing at least 24 samples each sample comprising a solution of the compound-of-interest and one or more components, wherein an amount of the compound-of-interest in each sample is less than about 1 gram;
(b) processing at least 24 of the samples under a set of processing parameters; and
(c) selecting the processed samples not having the solid-form to identify the set of processing parameters and/or components. - View Dependent Claims (129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140)
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141. A method to determine a set of processing parameters and/or components to dissolve or partially dissolve a solid-form of a compound-of-interest, comprising:
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(a) preparing at least 24 samples each sample comprising a solid-form of the compound-of-interest and one or more components, wherein an amount of the compound-of-interest in each sample is less than about 1 gram;
(b) processing at least 24 of the samples under a set of processing parameters; and
(c) selecting the processed samples wherein the solid-form dissolved or partially dissolved to identify the set of processing parameters and/or components. - View Dependent Claims (142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152)
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153. A method for determining conditions and/or components which produce a compound-of-interest or a diastereomeric derivative thereof in stereomerically enriched or conglomerate form, comprising:
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(a) preparing at least 24 samples each sample comprising the compound-of-interest or a diastereomeric derivative thereof and one or more components, wherein an amount of the compound-of-interest or the diastereomeric derivative in each sample is less than about 1 gram;
(b) processing at least 24 of the samples to generate an array wherein at least one of the processed samples comprises the compound-of-interest or the diastereomeric derivative in stereomerically enriched or conglomerate form; and
(c) selecting the stereomerically enriched or conglomerate samples in order to identify the set of conditions and/or components. - View Dependent Claims (154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169)
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Specification