Process of conducting high throughput testing high performance liquid chromatography

• US 10,302,602 B2
• Filed: 11/18/2015
• Issued: 05/28/2019
• Est. Priority Date: 11/18/2014
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Borsje, Eric, Rasmussen, Henrik Torstholm
• Primary Examiner(s): Schmitt, Benjamin R
• Application Number:
  US15/526,885
• Publication Number:
  US 20170356885A1
• Time in Patent Office: 1,287 Days
• Field of Search: 73 6141, 73 6152, 73 6155, 73 6159
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: G01N 1/4055 by solubility techniques
• CPC Class Codes: G01N 2013/006 Dissolution of tablets or the like
• CPC Class Codes: G01N 2035/00198 Dissolution analysers
• CPC Class Codes: G01N 2035/00495 Centrifuges
• CPC Class Codes: G01N 2035/00524 Mixing by agitating sample carrier
• CPC Class Codes: G01N 30/06 Preparation
• CPC Class Codes: G01N 30/88 Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
• CPC Class Codes: G01N 33/15 Medicinal preparations ; Physical properties thereof, e.g. dissolubility

Abstract

The present invention utilizes a high throughput testing (HTT) method of high performance liquid chromatography (HPLC) to validate samples of pharmaceutical compositions. In one embodiment, improved sample preparation techniques comprise adding the entire vial of a sample to a wide mouth disposable bottle, adding diluent, shaking overnight, and centrifuging.

Claims

1. A process of conducting high throughput high performance liquid chromatography (HPLC) comprising:

a) dropping containers of pre-weighed samples into plastic bottles;

b) adding solution to each set of container and bottle via a bottle top dispenser;

c) shaking each set of plastic bottle, container, and solution until sample is dissolved;

d) centrifuging each set of plastic bottle, container, and solution;

e) loading an aliquot of supernatant from the centrifuge step onto an HPLC column; and

f) running the column with a mobile phase.

2. The process of claim 1, wherein the containers of step a) are vials.

3. The process of claim 1, wherein the plastic bottles of step a) are high-density polyethylene (HDPE) bottles.

4. The process of claim 1, further comprising correlating the results from the process of claim 1 to process analytical technique (PAT) measurements for continuous manufacturing.

5. The process of claim 4, wherein continuous manufacturing is for a pharmaceutical composition.

6. The process of claim 5, wherein the pharmaceutical composition is a tablet.

7. The process of claim 6, wherein the tablet is for the treatment of a cystic fibrosis transmembrance conductance regulator (CFTR) mediated disease.

8. The process of claim 7, wherein the CFTR mediated disease is cystic fibrosis.

9. The process of claim 6, wherein the tablet comprises two active pharmaceutical ingredients (API).

10. The process of claim 9, wherein one API is a cystic fibrosis (CF) corrector.

11. The process of claim 9, wherein one API is a CF potentiator.

12. The process of claim 9, wherein one API is a CF corrector and the other API is a CF potentiator.

13. The process of claim 9, wherein one API is

14. The process of claim 9, wherein one API is

15. The process of claim 9, wherein one API is

16. The process of claim 15, wherein