TAMPER-RESISTANT PHARMACEUTICAL COMPOSITIONS OF OPIODS AND OTHER DRUGS

• US 20110142943A1
• Filed: 12/10/2010
• Published: 06/16/2011
• Est. Priority Date: 07/05/2002
• Status: Active Grant

• Current Assignee: Collegium Pharmaceutical Incorporated
• Original Assignee: Collegium Pharmaceutical Incorporated
• Inventors: Fleming, Alison B., Saim, Said, Rariy, Roman V., Varanasi, Ravi K., Hirsh, Jane C.
• Granted Patent: US 8,840,928 B2
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1664 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/1617
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5042 Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: B29C 70/60 comprising a combination of distinct filler types incorporated in matrix material, forming one or more layers, and with or without non-filled layers

Abstract

Tamper-resistant pharmaceutical compositions have been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. The tamper-resistant compositions retard the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract.

Claims

1. A pharmaceutical composition comprising a plurality of multiparticulates each multiparticulate comprising:

(a) one or more drugs prone to abuse; and

(b) one or more excipients comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof;

wherein the one or more drugs interact ionically with one or more of the excipients.

2. The composition of claim 1, wherein said drug is soluble in said one or more excipients when the one or more excipients are in their molten state.

3. The composition of claim 1, wherein the composition is a solid solution.

4. The composition of claim 1, wherein said plurality of multiparticulates have a span of less than 5.

5. The composition of claim 1, wherein said plurality of multiparticulates have a D(0.5) of less than about 750 μ

m.

6. The composition of claim 1, wherein said drug prone to abuse is an opioid analgesic.

7. The composition of claim 1, wherein the one or more excipients that interact ionically with said drug(s) are fatty acids.

8. The composition of claim 1, wherein the composition retards the release of a portion of the drug prone to abuse even if the physical integrity of the composition is compromised and the compromised composition is exposed to water.

9. The composition of claim 1 further comprising one or more anti-oxidants.

10. The composition of claim 1, wherein the one or more excipients have a low peroxide content in order to reduce oxidation of the drug or excipients.

11. The composition of claim 10, wherein the one or more excipients comprises carnauba wax having a peroxide value of less than 25 ppm.

12. The composition of claim 11, wherein the carnauba wax has a peroxide value of less than than 5 ppm.

13. The composition of claim 11, wherein the carnauba wax has a peroxide value of less than 3 ppm.

14. The composition of claim 1, further comprising one or more substances used to change the dissolution behavior or the physical and/or chemical stability of the formulation.

15. The composition of claim 14, wherein the one or more substances change the dissolution behavior of the formulation.

16. The composition of claim 14, wherein the one or more substances comprises rate-controlling materials.

17. The composition of claim 16, wherein said rate-controlling materials comprise starch derivatives, cellulose derivatives, acrylic polymers, polyvinyl pyrrolidone, alginic acid, lactose or mixtures thereof.

18. The composition of claim 14, wherein said rate-controlling materials comprise one or more pharmaceutically acceptable surfactants.

19. The composition of claim 18, wherein the one or more pharmaceutically acceptable surfactants comprise lecithin, sodium dodecyl sulfate, sodium salts of fatty acids, potassium salts of fatty acids, poloxamer, polyethoxylated castor oil, polyoxylglycerides, polysorbates, sorbitan stearate, or mixtures thereof.

20. The composition of claim 18, wherein the one or more surfactants are present in the multiparticulates, are applied to the surface to the multiparticulates, or are blended with the multiparticulates.

21. The composition of claim 1, wherein the multiparticulates are combined with one or more additional excipients and encapsulated into hard or soft shell capsules.

22. The composition of claim 21, wherein the one or more additional excipients are selected from the groups consisting of diluents, lubricants, gel forming excipients, and combinations thereof.

23. The composition of claim 21, wherein the hard shell capsules comprise hydroxypropylmethylcellulose.

24. A pharmaceutical composition comprising a plurality of multiparticulates each multiparticulate comprising:

(a) one or more drugs prone to abuse; and

(b) one or more excipients comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof comprising one or more ionic components;

wherein the ionic component of said one or more excipients interacts with said one or more drugs.

25. A method of making a pharmaceutical composition comprising:

(a) dispersing or dissolving a drug prone to abuse in one or more excipients comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof; and

(b) forming multiparticulates via a spray congealing process from the material obtained in step (a).

26. The method of claim 25, further comprising coating the multiparticulates obtained in step (b).

27. The method of claim 25, wherein the dissolving of said drug comprises a hot melt process.

28. The method of claim 25, wherein said dissolving comprises the use of a solvent or co-solvent.

29. The method of claim 28, wherein said spray congealing process comprises a spinning disc atomization process.

30. A pharmaceutical composition comprising a plurality of multiparticulates made by a process comprising forming multiparticulates via a spray congealing process from a dispersion or solution comprising:

(i) a drug prone to abuse; and

(ii) one or more excipients comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof.

31. The composition of claim 30, wherein the process further comprises optionally coating the formed multiparticulates.

32. A pharmaceutical composition made by a process comprising the steps of:

(a) dissolving a drug prone to abuse in one or more excipients comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof; and

(b) forming multiparticulates via a spray congealing process from the material obtained in step (a).

33. The pharmaceutical composition of claim 32, wherein the process further comprises coating the multiparticulates obtained in step (b).

34. A method of treating pain comprising administering to a human subject in need thereof, a therapeutically effective amount of a pharmaceutical composition comprising a plurality of multiparticulates, each multiparticulate comprising:

(a) one or more drugs prone to abuse; and

(b) one or more excipients comprising fats, fatty substances, waxes, wax-like substances or mixtures thereof;

wherein there is an ionic interaction between the one more drugs and one or more of the excipients.