Multiple-component solid phases containing at least one active pharmaceutical ingredient

Patent metadata

Field	Value
Publication number	US-10633344-B2
Application number	US-201414179862-A
Country	US
Kind code	B2
Filing date	Feb 13, 2014
Priority date	Mar 1, 2002
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

The subject invention concerns a method for identifying complementary chemical functionalities to form a desired supramolecular synthon. The subject invention also pertains to binary phase compositions comprising one or more pharmaceutical entities and methods for producing such compositions.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a co-crystal comprising supramolecular synthons, each supramolecular synthon formed from stoichiometric amounts of at least one active pharmaceutical ingredient (API) and at least one co-former and each supramolecular synthon comprising an API homosynthon formed via non-covalent hydrogen bonding,
wherein the API has a first chemical functionality that permits formation of API homosynthons through non-covalent hydrogen bonding when the API is in its pure form,
wherein the co-former has a second chemical functionality complimentary to the first chemical functionality via non-covalent hydrogen bonding,
wherein said co-former is a solid at room temperature and atmospheric pressure when the co-former is in its pure form, and
wherein supramolecular synthons are formed via non-covalent hydrogen bonding between the first chemical functionality of the API and the second chemical functionality of the co-former.

2. The pharmaceutical composition of claim 1 , wherein the at least one API participating in each supramolecular synthon is two APIs of the at least one API that are bonded to one another through hydrogen bonding to form at least one homosynthon dimer.

3. The pharmaceutical composition of claim 2 , wherein the at least one co-former is two of the co-former and the at least one API is two of the API, wherein the at least one homosynthon dimer is one homosynthon dimer, and wherein the supramolecular synthon forms a tetramer, the tetramer being comprised of the two co-formers and two APIs, and each co-former being attached to the homodimer by hydrogen bonds.

4. The pharmaceutical composition of claim 2 , wherein the at least one co-former is two co-formers, wherein the at least one homosynthon dimer is two homosynthon dimers, and wherein the supramolecular synthon results in a hexamer.

5. The pharmaceutical composition of claim 1 , wherein the supramolecular synthon comprises a plurality of the API and a plurality of the co-former, wherein the supramolecular synthon comprises a chain of homosynthon dimers, each homosynthon dimer formed by hydrogen bonding of one of the plurality of the API to another of the plurality of the API, and wherein the homosynthon dimers are bonded to the co-former by hydrogen bonding.

6. The pharmaceutical composition of claim 2 , wherein the at least one co-former participating in each supramolecular synthon is two co-formers forming a homosynthon.

7. The pharmaceutical composition of claim 1 , wherein the non-covalent bonding of said API homosynthons is carboxylic acid:carboxylic acid hydrogen bonding.

8. The pharmaceutical composition of claim 1 , wherein the non-covalent bonding of said API homosynthons is carboxamide:carboxamide hydrogen bonding.

9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a co-crystal comprising supramolecular synthons, each supramolecular synthon formed from stoichiometric amounts of at least one active pharmaceutical ingredient (API) and at least one co-former,
wherein the API has a first chemical functionality that permits formation of API homosynthons through non-covalent hydrogen bonding when the API is in its pure form,
wherein the co-former has a second chemical functionality complimentary to the first chemical functionality via non-covalent hydrogen bonding,
wherein said co-former is a solid at room temperature and atmospheric pressure when the co-former is in its pure form,
wherein supramolecular synthons are formed via non-covalent hydrogen bonding between the first chemical functionality of the API and the second chemical functionality of the co-former, and wherein the at least one API participating in each supramolecular synthon is two APIs and the at least one co-former is one co-former, and wherein each of the two APIs is bonded by non-covalent bonding to the one co-former.

10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a co-crystal comprising supramolecular synthons, each supramolecular synthon formed from stoichiometric amounts of at least one active pharmaceutical ingredient (API) and at least one co-former,
wherein the API has a first chemical functionality that permits formation of API homosynthons through non-covalent hydrogen bonding when the API is in its pure form,
wherein the co-former has a second chemical functionality complimentary to the first chemical functionality via non-covalent hydrogen bonding,
wherein said co-former is a solid at room temperature and atmospheric pressure when the co-former is in its pure form,
wherein supramolecular synthons are formed via non-covalent hydrogen bonding between the first chemical functionality of the API and the second chemical functionality of the co-former, and
wherein the first chemical functionality is (i) a carboxamide, (ii) a carbonyl, or (iii) an amine.

11. The pharmaceutical composition of claim 10 , wherein the supramolecular synthon comprises a heterosynthon dimer formed by non-covalent hydrogen bonding of the API to the co-former.

12. The pharmaceutical composition of claim 10 , wherein the supramolecular synthon comprises a plurality of the API and a plurality of the co-former, wherein the supramolecular synthon is a chain of supramolecular heterosynthons, each supramolecular heterosynthon formed by non-covalent hydrogen bonding of one API to one co-former, and wherein the supramolecular heterosynthons are bonded to one another by non-covalent hydrogen bonding.

13. The pharmaceutical composition of claim 10 , wherein the co-crystal is a hydrated co-crystal, wherein the supramolecular synthon comprises a plurality of the API and a plurality of the co-former, wherein the supramolecular synthon affords a sheet of the API, each of the APIs in the sheet bonded to one another and to a co-former by non-covalent hydrogen bonding to a water molecule.

14. The pharmaceutical composition of claim 10 , wherein the at least one co-former participating in each supramolecular synthon is two co-formers forming a homosynthon, the at least one API in each supramolecular synthon is two APIs, and wherein each of the two APIs is bonded by non-covalent bonding to one of the two co-formers.

15. The pharmaceutical composition of claim 10 , wherein the at least one API participating in each supramolecular synthon is two APIs and the at least one co-former participating in each supramolecular synthon is two co-formers forming a homosynthon, and wherein one of the two APIs is non-covalently bonded to one of the co-formers and the other of the two APIs is non-covalently bonded to the other of the two co-formers.

16. The pharmaceutical composition of claim 10 , wherein the supramolecular synthons are non-covalently bonded to one another by non-covalent bonding to a solvent molecule.

17. The pharmaceutical composition of claim 10 , wherein the second chemical functionality complimentary to the first chemical functionality is (i) two identical second chemical functionalities on the co-former, (ii) three identical second chemical functionalities on the co-former, or (iii) four identical second chemical functionalities on the co-former.

18. The pharmaceutical composition of claim 10 , wherein the first chemical functionality is a carboxamide.

19. The pharmaceutical composition of claim 10 , wherein the first chemical functionality is a carbonyl

Assignees

• Univ South Florida
• Univ Michigan Regents

Inventors

• Zaworotko Michael J
• Rodriguez-Hornedo Nair
• Moulton Brian

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K31/4166

  having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin · CPC title

• C07D213/82

  in position 3 · CPC title

• C07D213/69

  Two or more oxygen atoms · CPC title

• C07C51/412

  by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part · CPC title