Process of thermodynamical activation of water-insoluble drugs loaded into cross-linked polymers

• US 20040213840A1
• Filed: 12/24/2003
• Published: 10/28/2004
• Est. Priority Date: 06/29/2001
• Status: Active Grant

• Current Assignee: Adare Pharmaceuticals S.R.L. (Adare Pharmaceuticals, Inc.)
• Original Assignee: Adare Pharmaceuticals S.R.L. (Adare Pharmaceuticals, Inc.)
• Inventors: Magarotto, Lorenzo, Bresciani, Massimo, Dobetti, Luca
• Granted Patent: US 8,889,182 B2
• Time in Patent Office: Days
• US Class Current: 424/464
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds

Abstract

The present invention refers to a process to prepare a highly activated composite of one or more water-insoluble drugs, said process comprising the steps of: (a) subjecting said water-insoluble drug and a cross-linked polymer to co-grinding; (b) exposing the ground product of step a. to contact with water or water vapours. The resulting composite contains large amounts of drug in the easily soluble amorphous form, reduced amounts of drug in the nanocrystalline form, and is substantially free from practically insoluble drug crystals.

Claims

1. Process to prepare a highly activated composite of one or more water-insoluble drugs, comprising the following steps:

(a) subjecting said water-insoluble drug and a cross-linked polymer to co-grinding in dry conditions;

(b) exposing the ground product of step a. to contact with water or water vapours.

2. Process according to claim 1, where said co-grinding is performed under high energy conditions.

3. Process according to claim 1, where said cross-linked polymer is chosen from the group consisting of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, starch, sodium starch glycolate, pregelatinized starch, and polacrilin potassium.

4. Process according to claim 1, where said cross-linked polymer and said drug are used in a weight ratio comprised between 12:

1 and 0.5;

1.

5. Process according to claim 1, where said step a. is performed in a period comprised between 1 hour and 6 hours.

6. Process according to claim 1, where said step b. is performed in a period comprised between 5 minutes and 120 minutes.

7. Process according to claim 1, where, in step b., said ground powder is maintained in an agitated status.

8. Process according to claim 1 where in step b. the powder/water weight ratio is comprised between 1:

0.05 to 1;

5.

9. Process according to claim 1, where in step b. the powder/water weight ratio is comprised between 1:

0.1 and 1;

3.

10. Process according to claim 1, where the product of step b., optionally dried, is further processed into a pharmaceutical form.

11. A highly activated composite of a water-insoluble drug, obtainable by the process of claim 1.

12. A composite according to claim 11, formulated for pharmaceutical use.

13. A composite according to claim 11, in the form of tablets, minitablets, capsules, microcapsules, granules, pellets, soluble or dispersible powders, sachet dosage forms, suspensions, creams, ointments, implantable articles, programmed release devices.

14. A process according to claim 1, where said cross-linked polymer and said drug are used in a weight ratio comprised between 5:

1 to 1;

1.