US 2009/0022798 A1 · FORMULATIONS OF NONOPIOID AND CONFINED OPIOID ANALGESICS

Abstract

The preferred exemplary embodiments in the present application provide formulations and methods for the delivery of drugs, particularly drugs of abuse, having an abuse-relevant drug substantially confined in the core and a non-abuse relevant drug in a non-core region. These formulations have reduced potential for abuse. In the formulation, preferably the abuse relevant drug is an opioid and the non-abuse relevant drug is acetaminophen or ibuprofen. More preferably, the opioid is hydrocodone, and the non-abuse relevant analgesic is acetaminophen. In certain preferred embodiments, the dosage forms are characterized by resistance to solvent extraction; tampering, crushing or grinding. Certain embodiments of the inventions provide dosage forms that provide an initial burst of release of drug followed by a prolonged period of controllable drug release.

Claims92

Dependent claims

A pharmaceutical composition having a core and a non-core layer, comprising:

(a) hydrocodone, a pharmaceutically acceptable salt or a hydrate thereof, and
(b) acetaminophen or ibuprofen,
wherein at least 75% all of the hydrocodone, pharmaceutically acceptable salt or hydrate thereof is in the core,
wherein the acetaminophen or the ibuprofen is the non-core layer, and
wherein the composition is adapted so as to be useful for oral administration to a human 3, 2, or 1 times daily.

2 more elements

A pharmaceutical composition having a core and a non-core layer, comprising:

(a) an abuse-relevant drug, a pharmaceutically acceptable salt or a hydrate thereof and a non-abuse-relevant drug or a pharmaceutically acceptable salt thereof in the core layer, and
(b) a non-abuse-relevant drug, a pharmaceutically acceptable salt or a hydrate thereof in the non-core layer,
wherein the composition is adapted so as to be useful for oral administration to a human 3, 2, or 1 times daily;
and
wherein the composition is characterized by at least one of the following features:
i) the amount of abuse-relevant drug that is extracted from the composition by 40% aqueous ethanol within one hour at 37° C. in vitro is less than or equal 1.5 times the amount of the abuse-relevant drug that is extracted by 0.01 N hydrochloric acid in vitro within one hour at 37° C.,
ii) the composition does not break under a force of 150 newtons, preferably 300 newtons, more preferably 450 newtons, yet more preferably 500 newtons as measured by “Pharma Test PTB 501” hardness tester,
iii) the composition releases at least 20% of the abuse-relevant drug and not more than 45% of the abuse-relevant drug during the first hour of in vitro dissolution testing and preferably also during the first hour of in vivo testing,
iv) the composition releases a therapeutically effective dose of the non-abuse relevant drug within 1 to 2 hours after a single dose,
v) the composition releases a therapeutically effective dose of the non-abuse relevant drug and/or the abuse-relevant drug at 1 hour and at 12 hours after a single dose,
vi) in the composition, release of the abuse-relevant drug upon grinding increases by less than 2 to 3-fold, as compared to an intact tablet, when the composition is ground for 1 minute by a coffee-grinder at 20,000-50,000 rpm, in 40% aqueous ethanol for 1 hour at 37° C.,
vii) the composition when ground comprises a particulate size of about 2 cm to about 355 micrometer for about 20% of the fraction, greater than about 63 microns and less than about 355 microns for about 66% of the fraction and less than about 63 microns for about 14% of the fraction, as measured by a sieving test, or
viii) the composition is substantially smooth, wherein the Centre Line Average (CLA) is from about 0.1 to about 0.6, preferably from about 0.1 to about 0.4, and most preferably from about 0.1 to about 0.2.

10 more elements

A pharmaceutical composition having a core layer and a non-core layer,

(A) wherein the core layer comprises a mixture of:
(a) at least one opioid;
(b) at least one rate altering pharmaceutically acceptable polymer, copolymer, or a combination thereof;
(B) wherein the non-core layer comprises at least one non-opioid analgesic;
and
(C) wherein the composition is adapted so as to be useful for oral administration to a human 3, 2, or 1 times daily.

3 more elements

Dependencies are inferred from the claim text.

Formulations of nonopioid and confined opioid analgesics

Life of this patent

Formulations of nonopioid and confined opioid analgesics

Life of this patent

Abstract

Claims92