High-throughput formation, identification and analysis of diverse solid forms

• US 20050191614A1
• Filed: 01/31/2005
• Published: 09/01/2005
• Est. Priority Date: 01/07/2000
• Status: Abandoned Application

• Current Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Galakatos, Nicholas, Cima, Michael J., Lemmo, Anthony V., Putnam, David A., Levinson, Douglas
• Application Number:
  US11/051,698
• Publication Number:
  US 20050191614A1
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00587 High throughput processes
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: B01J 2219/00756 Compositions, e.g. coatings, crystals, formulations
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C30B 29/58 Macromolecular compounds
• CPC Class Codes: C30B 7/00 Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00
• CPC Class Codes: C40B 30/04 by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 21/23 : Bi-refringence
• CPC Class Codes: G01N 33/6845 : Methods of identifying protein-protein interactions in protein mixtures

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.

Claims

1. A system for detecting similarities among a plurality of samples, which comprises

a) a device for obtaining a spectrum for each sample;

and

b) a computer configured to analyze each of the spectra and to generate a plurality of sample groups, wherein each sample group corresponds to samples sharing at least one spectral feature and said sample groups are similar polymorphs, hydrates and solvates.

2. The system of claim 1 wherein the device is an infrared spectrometer, near infrared spectrometer, NMR spectrometer, X-ray diffractometer, neutron diffractometer, light microscope, electron microscope, second harmonic generator, circular dichroism spectrometer, linear dichroism spectrometer, differential scanning calorimeter, thermal gravimetric analyzer, or melting point analyzer.

3. The system of claim 1 wherein the device is a Raman spectrometer.

4. The system according to claim 1, wherein said samples are grouped into:

a. wells containing no precipitate;

b. wells with single polymorph;

c. wells with polymorph mixture;

d. wells with amorphous forms of pharmaceutical; and

e. wells with mixtures of;

     1) wells containing no precipitate;

     2) wells with single polymorph;

     3) wells with polymorph mixture; and

     4) wells with amorphous forms of pharmaceutical.

5. A system to identify solid-forms of a compound-of-interest, comprising:

a. a computer and 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. a 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.

6. The system of claim 5, wherein the detector is a video optical microscope, an image analyzer, an optical microscope, or a polarimeter.

7. The system of claim 5, further comprising an analyzer to analyze the detected solid-form.

8. The system of claim 7, wherein the analyzer is an infrared spectrophotometer, a second harmonic generation optical spectrometer, a mass spectrometer, a nuclear magnetic resonance spectrometer, a near infrared spectrophotometer, a Raman spectrophotometer, an x-ray powder diffractometer, a differential scanning calorimeter, a thermal gravimetric analyzer, a light microscope, or an electron microscope.

9. The system according to claim 5, wherein the system comprises a computer configured to analyze each of the spectra of the samples and to generate a plurality of sample groups, wherein each sample group corresponds to samples sharing at least one spectral feature.