Immediate release composition resistant to abuse by intake of alcohol

• US 9,358,295 B2
• Filed: 03/12/2015
• Issued: 06/07/2016
• Est. Priority Date: 02/06/2009
• Status: Expired due to Fees

• Current Assignee: Egalet, Ltd. (Assertio Holdings, Inc.)
• Original Assignee: Egalet, Ltd. (Assertio Holdings, Inc.)
• Inventors: Tygesen, Peter Holm, Oevergaard, Jan Martin, Oestman, Joakim
• Primary Examiner(s): Gembeh, Shirley V
• Application Number:
  US14/656,016
• Publication Number:
  US 20150313997A1
• Time in Patent Office: 453 Days
• Field of Search: 424/466, 424/495, 514/282, 514/629
• US Class Current: 1/1
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2893 Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61P 25/32 Alcohol-abuse

Abstract

The present invention provides immediate release pharmaceutical compositions for oral administration that are resistant to abuse by intake of alcohol.

Claims

1. An immediate release pharmaceutical composition resistant to alcohol-induced dose dumping, consisting of a single polymer matrix optionally provided with a coating, wherein the single polymer matrix has one or more drug substances dispersed therein and comprises (i) from about 30% to about 95% w/w of one or more polyglycols having a molecular weight of from about 900 to about 17,000 Daltons and (ii) one or more effervescent agents, and is resistant to alcohol-induced dose dumping.

2. The pharmaceutical composition according to claim 1, wherein the polymer matrix further comprises one or more disintegrants.

3. The pharmaceutical composition according to claim 2, wherein the one or more disintegrants is selected from the group consisting of sodium starch glycolate, povidone, sodium alginate, alginic acid, calcium alginate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, powdered cellulose, chitosan, croscarmellose sodium, crospovidone, cross-linked polyvinylpyrrolidone, hydroxypropyl starch, hydroxypropyl cellulose low-substituted, magnesium aluminium silicate, methylcellulose, microcrystalline cellulose, pregelatinized starch, docusae sodium, guar gum, and polacrilin potassium.

4. The pharmaceutical composition according to claim 2, wherein the one or more disintegrants are present in the composition at a total amount of from about 1% to about 60% by weight.

5. The pharmaceutical composition according to claim 2, wherein the one or more disintegrants are present in the composition at a total amount of from about 5% to about 50% by weight of the polymer matrix.

6. The pharmaceutical composition according to claim 2, wherein the total amount of the one or more effervescent agents and the one or more disintegrants is from about 1°

A w/w to about 80% by weight of the polymer matrix.

7. The pharmaceutical composition according to claim 1, wherein the one or more effervescent agents comprise an effervescent couple comprising a water soluble organic acid and a water soluble bicarbonate.

8. The pharmaceutical composition according to claim 7, wherein the water soluble organic acid is selected from the group consisting of citric acid, tartaric acid, succinic acid, malonic acid, benzoic acid, oxalic acid, malic acid and glutaric acid.

9. The pharmaceutical composition according to claim 7, wherein the water soluble bicarbonate comprises NaHCO₃.

10. The pharmaceutical composition according to claim 1, wherein the polymer matrix comprises a polyglycol having an average molecular weight selected from the group consisting of 1000, 1100, 1900, 2000, 2800, 2900, 3350, 4400, 5800, 6000, 8000, 8400, 10,000, 12,000, 14,600, and 17,000 Daltons.

11. The pharmaceutical composition according to claim 1, wherein the polymer matrix comprises one or more polyglycols having a molecular weight selected from the group consisting of PEG 3350, PEG 6000, and PEG 17,000.

12. The pharmaceutical composition according to claim 1, wherein the one or more drug substances is selected from the group consisting of anaesthetics, analgesics, opioids, antipyretics, antimigraine agents, antiepileptics, anti-parkinson agents, dopaminergic agents, antipsychotics, anxiolytics, sedatives, antidepressants, psychostimulating agents used for ADHD and nootropics, and agents used in addictive disorders.

13. The pharmaceutical composition according to claim 1, wherein the one or more drug substances is released from the composition in the stomach with a release profile that is dependent on the concentration of ethanol, such that an increased ethanol concentration results in a decreased rate of drug release.

14. The pharmaceutical composition according to claim 1, wherein the composition is resistant to alcohol-induced dose dumping when the alcohol is ingested together with the composition or within a period of up to 60 minutes before and up to 60 minutes after ingesting the composition.

15. The pharmaceutical composition according to claim 1, wherein the composition is resistant to abuse by intake of alcohol when the alcohol is ingested together with the composition or within a period of up to 60 minutes before and up to 60 minutes after the intake of the composition.

16. The pharmaceutical composition according to claim 1, wherein the ratio (R₅₀) of the time it takes to release 50% w/w of the drug substance from the pharmaceutical composition (t_50%) in a medium ethanol and dilute hydrochloric acid (pH 1.2) or phosphate buffer (pH 6.8) at a ratio of 40:

60 (v/v) to the time it takes to release 50% w/w of the drug substance from the pharmaceutical composition (t_50%)) in a medium of dilute hydrochloric acid (pH 1.2) or phosphate buffer (pH 6.8) is 1.5 or more, when the pharmaceutical composition is subject to in vitro dissolution test according to USP 32, NF 27, (711), Apparatus 2, paddle.

17. The pharmaceutical composition according to claim 1, wherein the polymer matrix is provided with the coating.

18. The pharmaceutical composition according to claim 17, wherein the coating is impermeable to and insoluble in an aqueous medium.

19. A method of administering an immediate release pharmaceutical composition to a patient that ingests three or more alcoholic beverages daily, comprising orally administering a pharmaceutical composition according to claim 1 to the patient.