INVESTIGATING DIFFERENT PHYSICAL AND/OR CHEMICAL FORMS OF MATERIALS

• US 20060025934A1
• Filed: 06/28/2005
• Published: 02/02/2006
• Est. Priority Date: 04/07/2000
• Status: Abandoned Application

• Current Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Cowell, Daniel, Stylianopoulos, Vassilis, Kobylecki, Ryszard Jurek
• Application Number:
  US11/160,552
• Publication Number:
  US 20060025934A1
• Time in Patent Office: Days
• US Class Current: 702/27
• 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 2219/00283 Reactor vessels with top opening
• CPC Class Codes: B01J 2219/00288 in the shape of syringes
• CPC Class Codes: B01J 2219/00308 interchangeably mounted in racks or blocks
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00416 Vacuum
• CPC Class Codes: B01J 2219/00418 using pressure
• 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 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00698 Measurement and control of process parameters
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50255 Multi-well filtration
• CPC Class Codes: C40B 40/00 Libraries per se, e.g. arrays, mixtures
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/115831 Condition or time responsive
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

Apparatus and a method are described for investigating polymorphs of a material, isomers of a material which allow different isomeric forms to be resolved, different hydrates/solvates and/or different salts of a material. The apparatus comprises an assembly (2) of reactor devices (6) arranged within a reactor body (8) which incorporates a heating/cooling block (10) and a stirrer block (12). A vessel support block (14) supports respective sample vessels (15) below each reactor device (6) for receiving material from the reactor devices. The apparatus includes a control unit (4) which includes a computer (16) which controls a robot for delivering materials to the reactor devices; a heating/cooling unit (18); a stirrer control unit (20); and a pressure unit (22) which controls the passage of material from the reactor devices (6) to the sample vessels (15).

Claims

1. A method of investigating the crystal habit of a selected material, comprising:

(A) providing a plurality of receptacles;

(B) depositing a selected quantity of a selected initial material into each said receptacle,

(C) subjecting said initial material to a first series of selected treatments, having selected first treatment variables, to form a resultant material in each of said receptacles wherein said treatments are controlled by a computer; and

(D) analyzing said resultant material to determine the crystal habit thereof and generating crystal habit data related thereto.

2. A method according to claim 1 including associating said crystal habit data of each said resultant material with said treatment variables.

3. A method according to claim 2 including storing said associated crystal habit data and said treatment in said computer.

4. A method according to claim 1 wherein said computer is programmed to select said treatment.

5. A method according to claim 1 including subjecting said resultant material to a second series of selected treatments.

6. A method according to claim 5 wherein said second series of selected treatments is selected by said computer depending upon the crystal habit data of said resultant material.

7. A method according to claim 1, wherein said first treatment variables include solvent variables.

8. A method according to claim 7, wherein said solvent variables are selected from one or more of the following:

(A) a first solvent variable relating to the number of solvents used for preparing said resultant material from said initial material;

(B) a second solvent variable relating to the timing of the addition of the solvent or solvents into said receptacle;

(C) a third solvent variable relating to the amount of a solvent or solvents used in a treatment; and

(D) a fourth solvent variable relating to the identity of a solvent or solvents used.

9. A method according to claim 8, wherein at least two of said solvent variables are varied in a single series of experiments and/or in multiple series of experiments.

10. A method according to claim 8, wherein the implementation of said solvent variables is under the control of said computer.

11. A method according to claim 1, wherein said first treatment variables includes a duration variable wherein said initial material is treated for a selected duration.

12. A method according to claim 1, wherein said first treatment variables includes a heating variable wherein said initial material is subjected to a heating means.

13. A method according to claim 12, wherein said heating variable is selected from one or more of the following:

(A) a first heating variable relating to the time of operation of said heating means;

(B) a second heating variable relating to the duration of operation of said heating means; and

(C) a third heating variable relating to whether operation of said heating means is continuous or in stages.

14. A method according to claim 1, wherein said first treatment variables includes a cooling variable wherein said initial material is subjected to a cooling means.

15. A method according to claim 1, wherein said first treatment variables includes an agitation variable wherein said initial material is subjected to agitation.

16. A method according to claim 15, wherein said agitation variable is selected from one or more of the following:

(A) a first agitation variable relating to the time of operation of an agitation means for agitating material;

(B) a second agitation variable relating to the duration of operation of said agitation means;

(C) a third agitation variable relating to whether operation of said agitation means is continuous or in stages; and

(D) a fourth agitation variable relating to the rate of operation of said agitation means.

17. A method according to claim 1, wherein a temperature profile is defined for each said receptacle and wherein temperature profile data relating thereto is stored in said computer.

18. A method according to claim 1 wherein said receptacles include a porous member that is porous to fluids but not to said initial material.

19. A method according to claim 1 including the application of pressure to said receptacles during said first series of selected treatments.

20. A method according to claim 19 wherein application of said pressure is controlled by said computer.

21. A method according to claim 1 wherein said first series of selected treatments includes the addition of liquid to at least one of said receptacles and wherein said liquid is removed from said receptacles and analyzed.

22. A method according to claim 1 including analyzing said crystal habit data to identify

(A) polymorphs of said initial material;

(B) hydrates/solvates of said initial material;

or

(C) salts of said initial material.

23. A method according to claim 1 wherein said initial material is subjected to a range of potential salt forming materials and wherein said resultant material formed thereby is a salt of said initial material.

24. A method according to claim 24 wherein said resultant material is in a crystalline form.

25. A method to determine the crystal habit of a selected material thereby to investigate polymorphs, hydrates/solvates, or salts of said selected material, comprising:

(A) providing a plurality of receptacles;

(B) depositing a selected quantity of a selected initial material into each said receptacle,

(C) subjecting said initial material to a first series of selected treatments, having selected first treatment variables, to form a first resultant material in each of said receptacles wherein said treatments are controlled by a computer; and

(D) analyzing said first resultant material to determine the crystal habit thereof; and

(E) generating first crystal habit data from said analysis of said first resultant material.

26. A method according to claim 25 including subjecting said first resultant material to a second series of selected treatments, having selected second treatment variables, to form a second resultant material.

27. A method according to claim 26 wherein said second treatment variables are selected by means of a computer.

28. A method according to claim 26 wherein said second treatment variables are different from said first treatment variables.

29. An investigation apparatus for investigating the crystal habit of an initial material wherein said initial material is subjected to selected treatment conditions thereby to investigate polymorphs, hydrates/solvates, or salts of said initial material, said investigation apparatus comprising

(A) a reactor assembly including

(1) a reactor body having an internal region;

and

(2) an array of receptacles disposed in the internal region adapted for receiving a selected quantify of the initial material to be investigated; and

(B) a control unit in communication with said reactor assembly and including a computer operative to control said selected treatment conditions.

30. An investigation apparatus according to claim 29 wherein said reactor assembly includes a heating/cooling block operative to subject a selected temperature to said initial material in said receptacles.

31. An investigation apparatus according to claim 29 wherein said reactor assembly includes a stirrer block operative to agitate said initial material in said receptacles.

32. An investigation apparatus according to claim 29 wherein said reactor assembly includes

(A) a plurality of collection vessels located in the interior region of said reactor assembly, each said collection vessel being in fluid communication with one of said receptacles;

and

(B) a collection vessel support block adapted to support said plurality of collection vessels.

33. An investigation apparatus according to claim 29 wherein said control unit operative to selectively vary the temperature during treatment of said initial material.

34. An investigation apparatus according to claim 29 wherein said control unit includes a stirrer control unit operative to selectively agitate said initial material during treatment thereof.

36. An investigation apparatus according to claim 29 where said receptacles are associated with means for condensing vapour for reducing loss of material therefrom by evaporation.

37. An investigation apparatus according to claim 36 wherein said receptacles include a porous member adapted to support said initial material when deposited therein, said porous member being porous to fluids but not to said initial material.

38. An investigation apparatus according to claim 37 including a pressure means operative to apply pressure within the internal region thereby to restrict the passage of fluids from said receptacles under gravity.

39. An investigation apparatus according to claim 38 wherein said pressure means is controlled by said computer.

40. An investigation apparatus according to claim 29 including

(A) a material supply means adapted to contain selected materials to be deposited into said receptacles;

and

(B) a delivery means for transporting said selected materials from said supply means to a selected one of said receptacles.

41. An investigation apparatus according to claim 29 including an input means for inputting analytical data relating to material produced after treatment of said initial material into said computer, wherein said computer is programmed to analyse data input into it and determine variables to be used in a subsequent investigation on the same initial material, using said apparatus.

42. An investigation apparatus according to claim 29 for making a library of products.

43. An investigation apparatus according to claim 29 for effecting automatically a multiplicity of treatments of an initial material which treatments differ in at least one experimental variable.

35. An investigation apparatus according to 29 wherein said control unit includes a pressure unit operative to control a selected pressure during treatment of said initial material.