COATING OF PARTICLES COMPRISING A PHARMACEUTICALLY ACTIVE INGREDIENT WITH A CARBONATE SALT OR PHOSPHATE SALT

• US 20130115301A1
• Filed: 12/20/2010
• Published: 05/09/2013
• Est. Priority Date: 12/22/2009
• Status: Abandoned Application

• Current Assignee: Lek Pharmaceuticals, d.d. (Novartis Ag)
• Original Assignee: Janko Jamnik, Milena Zorko, Lek Pharmaceuticals, d.d. (Novartis Ag)
• Inventors: Bele, Marjan, Kocevar, Klemen, Maver, Uros, Gaberscek, Miran
• Application Number:
  US13/521,902
• Publication Number:
  US 20130115301A1
• Time in Patent Office: Days
• US Class Current: 424/498
• CPC Class Codes: A61J 3/005 Coating of tablets or the like coating of sweetmeats or confectionery A23G3/20; coating of granules in general B01J2/006
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/501 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 9/501 Inorganic compounds
• CPC Class Codes: A61K 9/5089 Processes

Abstract

The present invention belongs to the field of pharmaceutical industry and relates to a process for coating a particle comprising a pharmaceutically active ingredient (API) comprising the steps of providing a composition comprising carbonate ions, phosphate ions, or a mixture thereof, providing a particle comprising an API, and precipitating a carbonate salt, a phosphate salt or a mixture thereof onto said particles.

The present invention is also directed to a particle comprising an API, wherein the particle is coated with a coating comprising a carbonate salt, phosphate salt, or mixture thereof, and to a pharmaceutical composition comprising said particles.

Moreover, the present invention is also directed to the use of said particles for preparing a medicament,

Claims

1. A process for coating a particle comprising a pharmaceutically active ingredient (API) comprising the steps of:

a) providing a composition comprising carbonate ions, phosphate ions, or a mixture thereof,

b) providing particle(s) comprising an API, and

c) precipitating a carbonate salt, a phosphate salt or a mixture thereof onto the particle(s) comprising the API, wherein the precipitation is carried out in a suspension having a pH of 4 or higher, wherein a solvent used is water optionally supplemented with organic solvent(s) up to 10 volume %, wherein API has a solubility of less than 1 mg/ml at pH 6.8 in the solvent(s) used in the process.

4. The process according to claim 1, wherein precipitation is achieved by combining a suspension comprising the particle(s) comprising the API and the composition of step a) with a solvent containing counter ions for the carbonate ions and/or phosphate ions, or by combining a suspension comprising the particle comprising the API and counter ions for the carbonate ions and/or phosphate ions with a solvent containing the composition of step a), or by combining a suspension comprising the API with a solvent containing the composition of step a) and another solvent containing the counter ions for the carbonate ions and/or phosphate ions.

5. The process according to claim 1, wherein the amount of the particle(s) comprising pharmaceutically active ingredient in the suspension during precipitation is in a range of from 0.1% to 50% w/w based on the total amount of solvent(s) used in the process.

6. The process according to claim 1, wherein the total amount of the carbonate ions, phosphate ions or mixture thereof is from 0.002 to 5 mol/L based on the total amount of solvent used in the process.

8. The process according to claim 1, wherein the carbonate ions, phosphate ions or mixture thereof are provided by one or more compounds selected from the group consisting of phosphorous acid, phosphorous acid water soluble salts, carbonic acid, carbonic acid water soluble salts, carbon dioxide, and mixtures thereof.

9. The process according to claim 4, wherein the counter ions for precipitating a carbonate salt, phosphate salt, or mixture thereof are provided by one or more compounds selected from the group consisting of calcium salts, magnesium salts, zinc salts, barium salts, strontium salts, copper salts, iron salts and mixtures thereof;

preferably from the group consisting of calcium salts, magnesium salts, zinc salts, barium salts and mixtures thereof;

more preferably from the group consisting of calcium salts, magnesium salts, zinc salts and mixtures thereof.

11. The process according to claim 1, wherein the suspension comprising the particle(s) comprising API further comprises an anti-aggregating agent.

12. The process according to claim 1, further comprising a step of precipitating a compound selected from the group consisting of surfactants, organic salts, saccharides, synthetic polymers, silica derivatives, waxes and salts, or a mixture thereof, on the surface of the particle comprising an API prior to precipitating the carbonate salt, the phosphate salt or mixtures thereof.

13. The process according to claim 1, further comprising a step of preparing a pharmaceutical composition.

2. A process for coating a particle comprising a pharmaceutically active ingredient (API), comprising the steps of:

a) providing a composition comprising carbonate ions, phosphate ions, or a mixture thereof,

b) providing particle(s) comprising an API, and

c) precipitating a carbonate salt, a phosphate salt or a mixture thereof onto the particle(s) comprising the API, and wherein the precipitation is achieved by gradually combining the carbonate ions, the phosphate ions or the mixture thereof with counter ions in the presence of the particle(s) comprising the API, wherein a solvent used is water optionally supplemented with organic solvent(s) up to 10 volume %, wherein API has a solubility of less than 1 mg/ml at pH 6.8 in the solvent(s) used in the process.

3. The process according to claim 2, wherein the gradually combining is achieved over a period of at least 1 minute.

7. The process according to claim 2, wherein the total amount of counter ions for precipitating the carbonate salt(s), phosphate salt(s), or mixture thereof is from 0.002 to 5 mol/L based on the total amount of solvent used in the process.

10. The process according to claim 2, wherein the pH of the suspension comprising particle(s) comprising API during the precipitation is 4 or higher.

14. A particle comprising a pharmaceutically active ingredient (API), the particle being coated with a coating comprising a carbonate salt, phosphate salt, or mixture thereof, wherein API has a solubility of less than 1 mg/ml at pH 6.8 in water.

15. The particle according to claim 14, wherein the particle size of the particle with said coating is at least 0.5 μ

m.

16. The particle according to claim 14, wherein the particle additionally comprises a layer underneath said coating, wherein the layer comprises, an amount of equal to or more than 50% w/w, at least one compound selected from the group consisting of surfactants, organic salts, saccharides, synthetic polymers, silica derivatives, waxes, salts and mixtures thereof.

17. A pharmaceutical composition comprising one or more particle(s) of claim 14.

18. (canceled)

19. A method of taste masking of a pharmaceutically active ingredient (API) comprising

a) providing a composition comprising carbonate ions, phosphate ions, or a mixture thereof,

b) providing particle(s) comprising an API, and

c) precipitating a carbonate salt, a phosphate salt or a mixture thereof onto the particle(s) comprising the API to form coated API particles, wherein the precipitation is carried out in a suspension having a pH of 4 or higher, wherein a solvent used is water optionally supplemented with organic solvent(s) up to 10 volume %, wherein API has a solubility of less than 1 mg/ml at pH 6.8 in the solvent(s) used in the process, wherein the taste of the API in the particles is masked.