IP Library Granted Patent US 7,709,634
Granted Patent B2
US 7,709,634 · App. 11/902,211 · Granted May 4, 2010

Amorphous form of rifaximin and processes for its preparation

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Quick Facts
Patent No.
US 7,709,634
App. No.
11/902,211
Granted
May 4, 2010
Kind
B2
Abstract

A stable amorphous form of rifaximin is disclosed. This form is chemically and polymorphically stable on storage and can be prepared by dissolving rifaximin in a solvent to form a solution, which is precipitated by adding an anti-solvent and isolating of the precipitated amorphous rifaximin as an end product.

Claims (22)

1. A compound, which is an amorphous form of rifaximin having substantially the same X-ray powder diffraction pattern as shown in FIG. 1 .

2. A process for the preparation of an amorphous form of rifaximin, said process comprising:

i. dissolving rifaximin in a solvent selected from the group consisting of C 3 to C 6 alkyl esters, C 2 to C 4 alcohols, C 3 to C 7 alkyl ketones, and mixtures thereof to form a solution;

ii. optionally distilling said solution;

iii. optionally filtering said solution;

iv. precipitating said solution by adding an anti-solvent selected from the group consisting of C 5 to C 10 hydrocarbons, C 4 to C 8 alkyl ethers, and mixtures thereof, or optionally precipitating by adding the solution to the anti-solvent,

v. isolating of said precipitated amorphous rifaximin; and

vi. optionally drying the amorphous rifaximin.

3. The process of claim 2 wherein said solvent is selected from methyl acetate, ethyl acetate, isopropyl acetate, isobutyl acetate, ethanol, isopropanol, 2-butanol, acetone, methyl iso-butyl ketone or mixtures thereof.

4. The process of claims 2 or 3 wherein the amount of said solvent is 1 to 25 volumes.

5. The process of claims 2 or 3 wherein the amount of solvent is 1.5 to 12 volumes.

6. The process of claims 2 or 3 wherein the amount of solvent is 2 to 6 volumes.

7. The process of claim 2 wherein the anti-solvent is selected from heptanes, methyl tert-butyl ether, or mixtures thereof.

8. The process of claims 2 or 7 wherein the amount of anti-solvent is 1 to 36 volumes.

9. The process of claims 2 or 7 wherein the amount of anti-solvent is 2 to 20 volumes.

10. The process of claims 2 or 7 wherein the amount of anti-solvent is 3 to 10 volumes.

11. The process of claim 2 wherein step (i) solution is maintained at a temperature of between 0° C. to reflux temperature.

12. The process of claim 2 wherein step (i) solution is maintained at a temperature of between 10° to 55° C.

13. The process of claim 2 step (i) solution is maintained at a temperature of between 15° to 45° C.

14. The process of claim 2 wherein the addition and precipitation temperature is −20° to 55° C.

15. The process of claim 2 wherein the addition and precipitation temperature is 0° to 45° C.

16. The process of claim 2 wherein the addition and precipitation temperature is 10° to 35° C.

Assignments (17)
RELEASE OF SECURITY INTEREST Recorded Nov 20, 2025
From: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
To: BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH AMERICAS, INC.
Reel/Frame 073654/0242 →
RELEASE OF SECURITY INTEREST Recorded Nov 20, 2025
From: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
To: ATON PHARMA, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH & LOMB PHARMA HOLDINGS CORP.; COMMONWEALTH LABORATORIES, LLC; DOW PHARMACEUTICAL SCIENCES, INC.; ECR PHARMACEUTICALS CO., INC.; LABORATOIRE CHAUVIN S.A.S.; MEDICIS PHARMACEUTICAL CORPORATION; ONPHARMA INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, LTD.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; SOLTA MEDICAL, INC.; SYNERGETICS USA, INC.; TECHNOLAS PERFECT VISION GMBH; VALEANT CANADA LP; VALEANT PHARMACEUTICALS INTERNATIONAL; VALEANT PHARMACEUTICALS INTERNATIONAL, INC.; VALEANT PHARMACEUTICALS NORTH AMERICA LLC; WIRRA IP PTY LIMITED; VALEANT PHARMA POLAND SP. Z O.O.; VALEANT PHARMACEUTICALS LUXEMBOURG S.A R.L.; VALEANT PHARMACEUTICALS IRELAND LIMITED
Reel/Frame 073637/0001 →
RELEASE OF SECURITY INTEREST Recorded Nov 20, 2025
From: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
To: BAUSCH HEALTH AMERICAS, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.
Reel/Frame 073637/0126 →
U.S. PATENT SECURITY AGREEMENT Recorded Jun 13, 2025
From: MEDICIS PHARMACEUTICAL CORPORATION; ORAPHARMA, INC.; BAUSCH HEALTH US, LLC (F/K/A VALEANT PHARMACEUTICALS NORTH AMERICA LLC); PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; BAUSCH HEALTH AMERICAS, INC.; SOLTA MEDICAL, INC.
To: JPMORGAN CHASE BANK, N.A.
Reel/Frame 071566/0200 →
U.S. PATENT SECURITY AGREEMENT Recorded Jun 13, 2025
From: MEDICIS PHARMACEUTICAL CORPORATION; ORAPHARMA, INC.; BAUSCH HEALTH US, LLC (F/K/A VALEANT PHARMACEUTICALS NORTH AMERICA LLC); PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; BAUSCH HEALTH AMERICAS, INC.; SOLTA MEDICAL, INC.
To: THE BANK OF NEW YORK MELLON
Reel/Frame 071564/0463 →
RELEASE OF SECURITY INTEREST Recorded Apr 8, 2025
From: BARCLAYS BANK PLC, AS COLLATERAL AGENT
To: SOLTA MEDICAL, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH IRELAND LIMITED (F/K/A/ VALEANT PHARMACEUTICALS IRELAND LIMITED); SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD; SANTARUS, INC.; MEDICIS PHARMACEUTICAL CORPORATION; HUMAX PHARMACEUTICAL S.A.; SOLTA MEDICAL IRELAND LIMITED; BAUSCH & LOMB MEXICO, S.A. DE C.V.; BAUSCH+LOMB OPS B.V.; BAUSCH HEALTH AMERICAS, INC.; BAUSCH HEALTH COMPANIES INC.; BAUSCH HEALTH HOLDCO LIMITED; BAUSCH HEALTH MAGYARORSZAG KFT (A/K/A BAUSCH HEALTH HUNGARY LLC); BAUSCH HEALTH POLAND SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA (F/K/A VALEANT PHARMA POLAND SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA); BAUSCH HEALTH US, LLC; BAUSCH HEALTH, CANADA INC. / SANTE BAUSCH, CANADA INC.; ICN POLFA RZESZOW SPOLKA AKCYJNA (A/K/A ICN POLFA RZESZOW S.A.); ORAPHARMA, INC.; PRZEDSIEBIORSTWO FARMACEUTYCZNE JELFA SPOLKA AKCYJNA (A/K/A PRZEDSIEBIORSTWO FARMACEUTYCZNE JELFA S.A.); SOLTA MEDICAL DUTCH HOLDINGS B.V.; V-BAC HOLDING CORP.; VRX HOLDCO LLC; 1261229 B.C. LTD.; 1530065 B.C. LTD.
Reel/Frame 070778/0199 →
SECURITY AGREEMENT (SECOND LIEN) Recorded Oct 5, 2022
From: BAUSCH HEALTH US, LLC; BAUSCH HEALTH AMERICAS, INC.; MEDICIS PHARMACEUTICAL CORPORATION; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; SOLTA MEDICAL, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 061606/0468 →
SECURITY AGREEMENT (FIRST LIEN) Recorded Oct 4, 2022
From: BAUSCH HEALTH US, LLC; BAUSCH HEALTH AMERICAS, INC.; MEDICIS PHARMACEUTICAL CORPORATION; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; SOLTA MEDICAL, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 061595/0066 →
SECURITY AGREEMENT Recorded Feb 10, 2022
From: BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH AMERICAS, INC.
To: THE BANK OF NEW YORK MELLON
Reel/Frame 059121/0001 →
SECURITY INTEREST Recorded Jun 8, 2021
From: BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; BAUSCH HEALTH AMERICAS, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 056811/0814 →
SECURITY INTEREST Recorded Mar 11, 2019
From: BAUSCH HEALTH AMERICAS, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH HEALTH US, LLC; SOLTA MEDICAL, INC.; MEDICIS PHARMACEUTICAL CORPORATION; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.
To: THE BANK OF NEW YORK MELLON, AS NOTES COLLATERAL AGENT
Reel/Frame 048556/0758 →
SECURITY INTEREST Recorded Feb 26, 2018
From: ATON PHARMA, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH & LOMB PHARMA HOLDINGS CORP.; COMMONWEALTH LABORATORIES, LLC; DOW PHARMACEUTICAL SCIENCES, INC.; ECR PHARMACEUTICALS CO., INC.; LABORATOIRE CHAUVIN S.A.S.; MEDICIS PHARMACEUTICAL CORPORATION; ONPHARMA INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, LTD.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; SOLTA MEDICAL, INC.; SYNERGETICS USA, INC.; TECHNOLAS PERFECT VISION GMBH; VALEANT CANADA LP; VALEANT PHARMACEUTICALS INTERNATIONAL; VALEANT PHARMACEUTICALS INTERNATIONAL, INC.; VALEANT PHARMACEUTICALS NORTH AMERICA LLC; WIRRA IP PTY LIMITED; VALEANT PHARMA POLAND SP. Z O.O.; VALEANT PHARMACEUTICALS LUXEMBOURG S.A R.L.; VALEANT PHARMACEUTICALS IRELAND LIMITED
To: THE BANK OF NEW YORK MELLON, AS COLLATERAL AGENT
Reel/Frame 045444/0634 →
SECURITY INTEREST Recorded Feb 26, 2018
From: ATON PHARMA, INC.; BAUSCH & LOMB INCORPORATED; BAUSCH & LOMB PHARMA HOLDINGS CORP.; COMMONWEALTH LABORATORIES, LLC; DOW PHARMACEUTICAL SCIENCES, INC.; ECR PHARMACEUTICALS CO., INC.; LABORATOIRE CHAUVIN S.A.S.; MEDICIS PHARMACEUTICAL CORPORATION; ONPHARMA INC.; ORAPHARMA, INC.; PRECISION DERMATOLOGY, INC.; SALIX PHARMACEUTICALS, LTD.; SALIX PHARMACEUTICALS, INC.; SANTARUS, INC.; SOLTA MEDICAL, INC.; SYNERGETICS USA, INC.; TECHNOLAS PERFECT VISION GMBH; VALEANT CANADA LP; VALEANT PHARMACEUTICALS INTERNATIONAL; VALEANT PHARMACEUTICALS INTERNATIONAL, INC.; VALEANT PHARMACEUTICALS NORTH AMERICA LLC; WIRRA IP PTY LIMITED; VALEANT PHARMA POLAND SP. Z O.O.; VALEANT PHARMACEUTICALS LUXEMBOURG S.A R.L.; VALEANT PHARMACEUTICALS IRELAND LIMITED
To: BARCLAYS BANK PLC, AS COLLATERAL AGENT
Reel/Frame 045444/0299 →
SECURITY AGREEMENT Recorded Apr 2, 2015
From: GLYCYX PHARMACEUTICALS, LTD.; SALIX PHARMACEUTICALS, INC.; SALIX PHARMACEUTICALS, LTD.; SANTARUS, INC.
To: BARCLAYS BANK PLC, AS COLLATERAL AGENT
Reel/Frame 035364/0396 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 3, 2013
From: OLON S.P.A.
To: SALIX PHARMACEUTICALS, INC.
Reel/Frame 030535/0348 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 26, 2013
From: APOTEX PHARMACHEM, INC.
To: OLON S.P.A.
Reel/Frame 030087/0878 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 20, 2007
From: KOTHAKONDA, KIRAN KUMAR; CHE, DAQING
To: APOTEX PHARMACHEM INC.
Reel/Frame 019918/0101 →