Oral dosage forms with therapeutically active agents in controlled release cores and immediate release gelatin capsule coats

• US 20040224020A1
• Filed: 12/18/2003
• Published: 11/11/2004
• Est. Priority Date: 12/18/2002
• Status: Abandoned Application

• Current Assignee: Grant L. Schoenhard
• Original Assignee: Grant L. Schoenhard
• Inventors: Schoenhard, Grant L.
• Application Number:
  US10/742,672
• Publication Number:
  US 20040224020A1
• Time in Patent Office: Days
• US Class Current: 424/471
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• 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 9/4816 Wall or shell material
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The present invention relates to oral dosage form with active agents in controlled release cores and in immediate release gelatin capsule coats.

Claims

1. An oral dosage form comprising (i) an controlled release core;

and (ii) an immediate release gelatin capsule around the controlled release core, wherein the controlled released core comprises at least one therapeutically active agent and at least one controlled release material; and

wherein the immediate release gelatin capsule comprises at least one therapeutically active agent.

2. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the controlled release core is the same as at least one therapeutically active agent in the immediate release gelatin capsule.

3. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the controlled released core is different from at least one therapeutically active agent in the immediate release gelatin capsule.

4. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the controlled release core is a drug.

5. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the controlled release core is an analgesic.

6. The oral dosage_form of claim 1, wherein at least one therapeutically active agent in the controlled release core comprises an opioid agonist.

7. The oral dosage form of claim 6, wherein the opioid agonist in the controlled release core comprises at least one of the following:

alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, cyclorphen, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxyaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydroxymethylmorphinan, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylmorphine, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, ohmefentanyl, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, pholcodine, piminodine, piritramide, propheptazine, promedol, profadol, properidine, propiram, propoxyphene, remifentanyl, sufentanyl, tramadol, tilidine, or salts thereof.

8. The oral dosage form of claim 7, wherein the opioid agonist in the controlled release core comprises oxycodone.

9. The oral dosage form of claim 6, wherein at least one therapeutically active agent in the controlled release core further comprises an opioid antagonist.

10. The oral dosage form of claim 9, wherein the opioid antagonist in the controlled release core comprises at least one of the following:

naltrexone, naloxone, nalmefene, methylnaltrexone, naloxone methiodide, nalorphine, naloxonazine, nalide, nalmexone, nalbuphine, nalorphine dinicotinate, naltrindole, naltrindole isothiocyanate, naltriben, nor-binaltorphimine, b-funaltrexamine, BNTX, cyprodime, ICI-174-864, LY117413, MR2266, or an opioid antagonist having the same pentacyclic nucleus as nalmefene, naltrexone, buprenorphine, levorphanol, meptazinol, pentazocine, or dezocine.

11. The oral dosage form of claim 9, wherein the opioid antagonist in the controlled release core comprises naltrexone.

12. The oral dosage form of claim 1, wherein the at least one therapeutically active agent in the immediate release gelatin capsule is a drug.

13. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the immediate release gelatin capsule is an analgesic.

14. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises an opioid agonist.

15. The oral dosage form of claim 14, wherein the opioid agonist in the immediate release gelatin capsule comprises at least one of the following:

alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, cyclorphen, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxyaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydroxymethylmorphinan, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylmorphine, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, ohmefentanyl, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, pholcodine, piminodine, piritramide, propheptazine, promedol, profadol, properidine, propiram, propoxyphene, remifentanyl, sufentanyl, tramadol, tilidine, or salts thereof.

16. The oral dosage form of claim 14, wherein the opioid agonist in the immediate release gelatin capsule comprises oxycodone.

17. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises an opioid antagonist.

18. The oral dosage form of claim 17, wherein the opioid antagonist in the immediate release gelatin capsule comprises at least one of the following:

naltrexone, naloxone, nalmefene, methylnaltrexone, naloxone methiodide, nalorphine, naloxonazine, nalide, nalmexone, nalbuphine, nalorphine dinicotinate, naltrindole, naltrindole isothiocyanate, naltriben, nor-binaltorphimine, b-funaltrexamine, BNTX, cyprodime, ICI-174-864, LY117413, MR2266, or an opioid antagonist having the same pentacyclic nucleus as nalmefene, naltrexone, buprenorphine, levorphanol, meptazinol, pentazocine, or dezocine.

19. The oral dosage form of claim 17, wherein the opioid antagonist in the immediate release gelatin capsule comprises naltrexone.

20. The oral dosage form of claim 17, wherein at least one therapeutically active agent in the immediate release gelatin capsule further comprises an opioid agonist.

21. The oral dosage form of claim 20, wherein the opioid agonist in the immediate release gelatin capsule comprises at least one of the following:

alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, cyclorphen, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxyaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydroxymethylmorphinan, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylmorphine, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, ohmefentanyl, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, pholcodine, piminodine, piritramide, propheptazine, promedol, profadol, properidine, propiram, propoxyphene, remifentanyl, sufentanyl, tramadol, tilidine, or salts thereof.

22. The oral dosage form of claim 20, wherein the opioid agonist in the immediate release gelatin capsule comprises oxycodone.

23. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the controlled released core comprises an opioid agonist;

and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises an opioid antagonist.

24. The oral dosage form of claim 23, wherein the opioid agonist in the controlled released core comprises at least one of the following:

alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, cyclorphen, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxyaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydroxymethylmorphinan, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylmorphine, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, ohmefentanyl, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, pholcodine, piminodine, piritramide, propheptazine, promedol, profadol, properidine, propiram, propoxyphene, remifentanyl, sufentanyl, tramadol, tilidine, or salts thereof; and

wherein the opioid antagonist in the immediate release gelatin capsule comprises at least one of the following;

naltrexone, naloxone, nalmefene, methylnaltrexone, naloxone methiodide, nalorphine, naloxonazine, nalide, nalmexone, nalbuphine, nalorphine dinicotinate, naltrindole, naltrindole isothiocyanate, naltriben, nor-binaltorphimine, b-funaltrexamine, BNTX, cyprodime, ICI-174-864, LY117413, MR2266, or an opioid antagonist having the same pentacyclic nucleus as nalmefene, naltrexone, buprenorphine, levorphanol, meptazinol, pentazocine, or dezocine.

25. The oral dosage form of claim 23, wherein at least one therapeutically active agent in the controlled released core comprises oxycodone, and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises naltrexone.

26. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the controlled released core comprises an opioid agonist;

and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises an opioid antagonist and an opioid agonist.

27. The oral dosage form of claim 26, wherein the opioid agonist in the controlled released core and in the immediate release gelatin capsule comprises at least one of the following:

alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, cyclorphen, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxyaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydroxymethylmorphinan, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylmorphine, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, ohmefentanyl, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, pholcodine, piminodine, piritramide, propheptazine, promedol, profadol, properidine, propiram, propoxyphene, remifentanyl, sufentanyl, tramadol, tilidine, or salts thereof; and

wherein the opioid antagonist in the immediate release gelatin capsule comprises at least one of the following;

naltrexone, naloxone, nalmefene, methylnaltrexone, naloxone methiodide, nalorphine, naloxonazine, nalide, nalmexone, nalbuphine, nalorphine dinicotinate, naltrindole, naltrindole isothiocyanate, naltriben, nor-binaltorphimine, b-funaltrexamine, BNTX, cyprodime, ICI-174-864, LY117413, MR2266, or an opioid antagonist having the same pentacyclic nucleus as nalmefene, naltrexone, buprenorphine, levorphanol, meptazinol, pentazocine, or dezocine.

28. The oral dosage form of claim 26, wherein at least one therapeutically active agent in the controlled released core comprises oxycodone;

and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises naltrexone and oxycodone.

29. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the controlled released core comprises an opioid agonist and an opioid antagonist;

and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises an opioid antagonist.

30. The oral dosage form of claim 29, wherein the opioid agonist in the controlled released core comprises at least one of the following:

alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, cyclorphen, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxyaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydroxymethylmorphinan, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylmorphine, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, ohmefentanyl, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, pholcodine, piminodine, piritramide, propheptazine, promedol, profadol, properidine, propiram, propoxyphene, remifentanyl, sufentanyl, tramadol, tilidine, or salts thereof; and

wherein the opioid antagonist in the controlled released core and in the immediate release gelatin capsule comprises at least one of the following;

naltrexone, naloxone, nalmefene, methylnaltrexone, naloxone methiodide, nalorphine, naloxonazine, nalide, nalmexone, nalbuphine, nalorphine dinicotinate, naltrindole, naltrindole isothiocyanate, naltriben, nor-binaltorphimine, b-funaltrexamine, BNTX, cyprodime, ICI-174-864, LY117413, MR2266, or an opioid antagonist having the same pentacyclic nucleus as nalmefene, naltrexone, buprenorphine, levorphanol, meptazinol, pentazocine, or dezocine.

31. The oral dosage form of claim 29, wherein at least one therapeutically active agent in the controlled released core comprises oxycodone and naltrexone;

and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises naltrexone.

32. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the controlled released core comprises an opioid agonist and an opioid antagonist;

and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises an opioid agonist and an opioid antagonist.

33. The oral dosage form of claim 32, wherein the opioid agonist in the controlled released core and in the immediate release gelatin capsule comprises at least one of the following:

alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, cyclorphen, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxyaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydroxymethylmorphinan, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylmorphine, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, ohmefentanyl, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, pholcodine, piminodine, piritramide, propheptazine, promedol, profadol, properidine, propiram, propoxyphene, remifentanyl, sufentanyl, tramadol, tilidine, or salts thereof; and

wherein the opioid antagonist in the controlled released core and in the immediate release gelatin capsule comprises at least one of the following;

naltrexone, naloxone, nalmefene, methylnaltrexone, naloxone methiodide, nalorphine, naloxonazine, nalide, nalmexone, nalbuphine, nalorphine dinicotinate, naltrindole, naltrindole isothiocyanate, naltriben, nor-binaltorphimine, b-funaltrexamine, BNTX, cyprodime, ICI-174-864, LY117413, MR2266, or an opioid antagonist having the same pentacyclic nucleus as nalmefene, naltrexone, buprenorphine, levorphanol, meptazinol, pentazocine, or dezocine.

34. The oral dosage form of claim 32, wherein at least one therapeutically active agent in the controlled released core comprises oxycodone and naltrexone;

and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises oxycodone and naltrexone.

35. The oral dosage form of claim 1, wherein at least one therapeutically active agent in the controlled released core comprises an opioid agonist;

and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises an opioid agonist.

36. The oral dosage form of claim 35, wherein the opioid agonist in the controlled released core and in the immediate release gelatin capsule comprises at least one of the following:

alfentanil, allylprodine, alphaprodine, anileridine, apomorphine, apocodeine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, cyclorphen, cyprenorphine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxyaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydroxymethylmorphinan, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, methylmorphine, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, ohmefentanyl, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, pholcodine, piminodine, piritramide, propheptazine, promedol, profadol, properidine, propiram, propoxyphene, remifentanyl, sufentanyl, tramadol, tilidine, or salts thereof.

37. The oral dosage form of claim 35, wherein at least one therapeutically active agent in the controlled released core comprises oxycodone;

and wherein at least one therapeutically active agent in the immediate release gelatin capsule comprises oxycodone.

38. The oral dosage form of claims 6-8 and 23-37, wherein the opioid agonist in the controlled release core is in a subanalgesic amount.

39. The oral dosage form of claims 6-8 and 23-37, wherein the opioid agonist in the controlled release core is in an amount ranging from about 0.1 mg to about 300 mg.

40. The oral dosage form of claims 17-34 wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg.

41. The oral dosage of claims 17-36 wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg and wherein the opioid agonist in the immediate release gelatin capsule is in an subanalgesic amount.

42. The oral dosage of claims 17-36 wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg and wherein the opioid agonist in the immediate release gelatin capsule is in an amount ranging from about 0.1 mg to about 300 mg.

43. The oral dosage form of claims 23, 24, or 25, wherein the opioid agonist in the controlled release core is in an subanalgesic amount;

and wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg.

44. The oral dosage form of claims 23, 24, or 25, wherein the opioid agonist in the controlled release core is in an amount ranging from about 0.1 mg to about 300 mg;

and wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg.

45. The oral dosage form of claims 26, 27, or 28, wherein the opioid agonist in the controlled release core is in an analgesic or subanalgesic amount;

wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg; and

wherein the opioid agonist in the immediate release gelatin capsule is in an subanalgesic amount.

46. The oral dosage forms of claims 26, 27, or 28, wherein the opioid agonist in the controlled release core is in an amount ranging from about 0.1 mg to about 300 mg;

wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg; and

wherein the opioid agonist in the immediate release gelatin capsule is in an amount ranging from about 0.1 mg to about 300 mg.

47. The oral dosage form of claims 29, 30, or 31, wherein the opioid agonist in the controlled release core is in an subanalgesic amount;

wherein the opioid antagonist in the controlled release core is in an amount ranging from about 0.001 mg to less than about 0.5 mg; and

wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg.

48. The oral dosage form of claims 29, 30, or 31, wherein the opioid agonist in the controlled release core is in an amount ranging from about 0.1 mg to about 300 mg;

wherein the opioid antagonist in the controlled release core is in an amount ranging from about 0.001 mg to less than about 0.5 mg; and

wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg.

49. The oral dosage form of claims 32, 33, or 34, wherein the opioid agonist in the controlled release core is in an subanalgesic amount;

wherein the opioid antagonist in the controlled release core is in an amount ranging from about 0.001 mg to less than about 0.5 mg;

wherein the opioid agonist in the immediate release gelatin capsule is in an subanalgesic amount; and

wherein the opioid antagonist in s the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg.

50. The oral dosage form of claims 32, 33, or 34, wherein the opioid agonist in the controlled release core is in an amount ranging from about 0.1 mg to about 300 mg;

wherein the opioid antagonist in the controlled release core is in an amount ranging from about 0.001 mg to less than about 0.5 mg;

wherein the opioid agonist in the immediate release gelatin capsule is in an amount ranging from about 0.1 mg to about 300 mg; and

wherein the opioid antagonist in the immediate release gelatin capsule is in an amount ranging from about 0.001 mg to less than about 0.5 mg.

51. The oral dosage form of claims 35, 36, or 37, wherein the opioid agonist in the controlled release core is in an analgesic or subanalgesic amount;

and wherein the opioid agonist in the immediate release gelatin capsule is in an analgesic or subanalgesic amount.

52. The oral dosage form of claims 35, 36, or 37, wherein the opioid agonist in the controlled release core is in an amount ranging from about 0.1 mg to about 300 mg;

and wherein the opioid agonist in the immediate release gelatin capsule is in an amount ranging from about 0.1 mg to about 300 mg.

53. The oral dosage form of claim 1, wherein the controlled release core comprises at least one therapeutically active agent and at least one controlled release material, wherein the agent or the material are formulated as a liquid, granulate, particulate, pellet, or bead.

54. The oral dosage form of claim 1, wherein the controlled release material comprises at least one hydrophobic or hydrophilic polymer.

55. The oral dosage form of claim 1, wherein the controlled release material comprises at least one acrylate or at least one methacrylate polymer.

56. The oral dosage form of claim 54, wherein the controlled release material comprises at least one acrylic polymer.

57. The oral dosage form of claim 56, wherein at least one acrylic polymer is cationic, anionic, or non-ionic.

58. The oral dosage form of claim 57, wherein at least one acrylic polymer is an acrylic acid copolymer, a methacrylic acid copolymer, a methyl methacrylate copolymer, an ethoxyethyl methacrylate copolymer, a cyanoethyl methacrylate copolymer, a methyacryacylic acid copolymer, or an aminoalkyl methacrylate copolymer.

59. The oral dosage form of claim 1, wherein the controlled release material comprises at least one propylene glycol, glyceryl, diethylaminoethyl, glycol, amide, long chain fatty acid amide, long chain fatty alcohol, or long chain ester.

60. The oral dosage form of claim 59, wherein the long chain fatty acid amide comprises at least one of the following:

N,N′

-ethylene disteramide, steramide monoethanolamine (MEA), steramide diethanolamine (DEA), ethylene bisteramide, or cocoamine oxide.

61. The oral dosage form of claim 59, wherein the long chain fatty alcohol comprises at least one cetyl alcohol or steryl alcohol.

62. The oral dosage form of claim 59, wherein the long chain ester comprises at least one of the following:

myristyl myristate, beheny erucate, glyceryl phosphates, or acetylated sucrose distearate.

63. The oral dosage form of claim 1, wherein the controlled release material comprises at least one of the following:

64. The oral dosage form of claim 63, wherein at least one of the alkanoyl, hydroxy-substituted alkanoyl, or acyloxy-substituted alkanoyl groups in compounds I, II, III, IV, V, VI, VII, or VIII, further comprises at least one alkanoyl moiety comprising from about 2 to about 6 carbon atoms.

65. The oral dosage form of claim 63, wherein at least one of compounds I, II, III, IV, V, VI, VII, or VIII comprises at least one hydroxy-substituted alkanoyl moiety or acyloxy-substituted alkanoyl moiety.

66. The oral dosage form of claim 65, wherein the at least one hydroxy-substituted alkanoyl moiety or acyloxy-substituted alkanoyl moiety further comprises at least one alkanoyl moieties comprising from about 2 to about 6 carbon atoms.

67. The oral dosage form of claim 62, wherein at least one acyl group of the acyloxy-substituted alkanoyl moiety is of the form R₉CO—

, and wherein R₉ comprises at least one oxy-substituted alkyl group comprising from about 2 to about 6 carbon atoms.

68. The oral dosage form of claim 67, wherein the oxy-substituted alkyl group of R₉ is a hydroxy substitution or a substitution comprising at least one acyl moiety.

69. The oral dosage form of claim 68, wherein R₉ comprises at least one oligomer of oxy-substituted carboxylic acids, wherein the oxy-substituted carboxylic acids are linked by an ester bond between (i) the hydroxy group of at least one acid monomer, and (ii) the carboxy group of another acid monomer.

70. The oral dosage form of claim 69, wherein R₉ comprises from about 1 to about 5 lactide or glycolide units.

71. The oral dosage form of claim 70, wherein R₉ comprises a mixture comprising at least one lactide unit and at least one glycolide unit.

72. The oral dosage form of claim 69, wherein R₉ comprises a mixture comprising at least one lactic acid unit and at least one glycolic acid unit, and wherein the mixture does not comprise lactide units or glycolide units.

73. The oral dosage of claim 63, wherein R₁, R₂, and R₃ of compound II is lactoyl, polylactoyl, ε

-caproyl, hydroxyacetyl, polyhydroxyacetyl, polylactoyl, or polyhydroxyacetyl.

74. The oral dosage of claim 63, wherein R₁, R₂, and R₃ of compound III is lactoyl, polylactoyl, ε

-caproyl, hydroxyacetyl, polyhydroxyacetyl, polylactoyl, or polyhydroxyacetyl.

75. The oral dosage form of claim 1, wherein at least one controlled release material comprises sucrose acetate isobutyrate (SAIB).

76. The oral dosage form of claim 2, wherein at least one controlled release material comprises sucrose acetate isobutyrate (SAIB).

77. The oral dosage form of claim 3, wherein at least one controlled release material comprises sucrose acetate isobutyrate (SAIB).

78. The oral dosage form of claims 1, 2, or 3, wherein the immediate release gelatin capsule is the in the form of a soft gelatin capsule or a hard gelatin capsule.

79. The oral dosage form of claim 78, wherein the controlled release core is in the form of a liquid, capsule, tablet, or caplet.

80. The oral dosage form of claim 1, wherein the immediate release gelatin capsule is the in the form of a soft gelatin capsule, and wherein the controlled release core is in the form of a tablet.

81. The oral dosage form of claim 1, wherein the immediate release gelatin capsule is in the form of a soft gelatin capsule, and wherein the controlled release core is in the form of a tablet.

82. The oral dosage form of claim 1, wherein the immediate release gelatin capsule is the in the form of a soft gelatin capsule, and wherein the controlled release core is in the form of a capsule.

83. The oral dosage form of claims 1, 2, or 3, further comprising at least one enteric coating.

84. The oral dosage form of claim 83, wherein at least one enteric coating is affixed over the controlled release core and under the immediate release gelatin capsule.

85. The oral dosage form of claim 83, wherein the immediate release gelatin capsule coating is an enteric coating.

86. The oral dosage form of claim 83, wherein the immediate release gelatin capsule is in the form of a soft gelatin capsule, and wherein the controlled release core is in the form of a liquid, tablet, or capsule.

87. The oral dosage form of claim 1, further comprising at least one of the following:

pharmaceutically acceptable salt, excipient, carrier, diluent, adjuvant, dispersing agent, suspending agent, acidifying agent, adsorbent, alkalizing agent, anti-adherent, antioxidant, binder, buffering agent, colorant, complexing agent, filler, direct compression excipient, disintegrant, flavorant, fragrance, glidant, lubricant, opaquant, plasticizer, polishing agent, preservative, or sweetening agent.

88. The oral dosage form of claim 87, wherein the excipient is Explotab®

.

89. The oral dosage form of claim 83, further comprising Explotab®

.

90. The oral dosage form of claim 84, further comprising Explotab®

.

91. The oral dosage form of claim 85, further comprising Explotab®

.

92. The oral dosage form of claim 86, further comprising Explotab®

.

103. The oral dosage form of any of the claims 1-92, wherein the controlled release core further comprises at least one immediate release component comprising at least one therapeutically active agent.

104. The oral dose form of any of claims 1-92 and 103 wherein the controlled released core is an inner controlled released core, and wherein the immediate release gelatin capsule is an outer immediate release gelatin capsule.

93. A method of making an oral dosage form comprising:

(i) preparing a controlled release core, wherein the controlled released core comprises at least one therapeutically active agent and at least one controlled release material; and

(ii) an immediate release gelatin capsule around the controlled release core, wherein the immediate release gelatin capsule coating comprises at least one therapeutically active agent.

94. The method of claim 93, wherein the oral dosage form comprises the same therapeutically active agent in both the controlled release core and the immediate release gelatin capsule.

95. A method of selectively enhancing analgesic potency of an opioid agonist or attenuating an adverse side effect of the opioid agonist in a human subject comprising:

(i) administering to the human subject an oral dosage form comprising;

(a) a controlled release core; and

(b) an immediate release gelatin capsule around the controlled release core;

wherein the controlled released core comprises at least one opioid agonist and at least one controlled release material;

wherein the immediate release gelatin capsule coating comprises at least one opioid antagonist, and wherein the antagonist enhances the analgesic potency of the opioid agonist or attenuates an adverse side effect of the agonist in the human subject.

96. The method of claim 95, wherein the opioid agonist comprises oxycodone and the antagonist comprises naltrexone.

97. A method of selectively enhancing analgesic potency of an opioid agonist or attenuating an adverse side effect of the opioid agonist in a human subject comprising:

(i) administering to the human subject an oral dosage form comprising;

(a) a controlled release core; and

(b) an immediate release gelatin capsule around the controlled release core;

wherein the controlled released core comprises at least one opioid agonist and at least one controlled release material;

wherein the immediate release gelatin capsule comprises at least one opioid agonist and at least one opioid antagonist, and wherein the antagonist enhances the analgesic potency of the opioid agonist or attenuates an adverse side effect of the agonist in the human subject.

98. The method of claim 97, wherein the opioid agonist in the controlled release core comprises oxycodone, wherein the opioid agonist in the immediate release gelatin capsule comprises oxycodone, and wherein the opioid antagonist in the immediate release gelatin capsule comprises naltrexone.

99. A method of selectively enhancing analgesic potency of an opioid agonist or attenuating an adverse side effect of the opioid agonist in a human subject comprising:

(i) administering to the human subject an oral dosage form comprising;

(a) a controlled release core; and

(b) an immediate release gelatin capsule coating around the controlled release core;

wherein the controlled released core comprises at least one opioid agonist, at least one opioid antagonist, and at least one controlled release material;

wherein the immediate release gelatin capsule comprises at least one opioid agonist, and wherein the antagonist enhances the analgesic potency of the opioid agonist or attenuates an adverse side effect of the agonist in the human subject.

100. The method of claim 99, wherein the opioid agonist in the controlled release core comprises oxycodone, wherein the opioid antagonist in the controlled release core comprises naltrexone, and wherein the opioid agonist in the immediate release gelatin capsule comprises oxycodone.

101. A method of selectively enhancing analgesic potency of an opioid agonist or attenuating an adverse side effect of the opioid agonist in a human subject comprising:

(i) administering to the human subject an oral dosage form comprising;

(a) a controlled release core; and

(b) an immediate release gelatin capsule around the controlled release core;

wherein the controlled released core comprises at least one opioid agonist, at least one opioid antagonist, and at least one controlled release material;

wherein the immediate release gelatin capsule comprises at least one opioid agonist and at least one opioid antagonist, and wherein the antagonist enhances the analgesic potency of the opioid agonist or attenuates an adverse side effect of the agonist in the human subject.

102. The method of claim 101, wherein the opioid agonist in the controlled release core comprises oxycodone, wherein the opioid antagonist in the controlled release core comprises naltrexone, wherein the opioid agonist in the immediate release gelatin capsule comprises oxycodone, and wherein the opioid antagonist in the immediate release gelatin capsule comprises naltrexone.