Modafinil modified release pharmaceutical compositions

• US 8,153,159 B2
• Filed: 09/17/2004
• Issued: 04/10/2012
• Est. Priority Date: 09/18/2003
• Status: Expired due to Fees

• Current Assignee: Cephalon Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cephalon Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Parikh, Alpa, Patel, Piyush
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): YOUNG, MICAH PAUL
• Application Number:
  US10/944,528
• Publication Number:
  US 20050095294A1
• Time in Patent Office: 2,762 Days
• Field of Search: 424/471, 424/464, 424/465, 424/489, 424/458, 424/474, 424/476, 424/490
• US Class Current: 424/490
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• 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 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Pharmaceutical compositions comprising modafinil. The pharmaceutical compositions can have a release profile which is different than that of traditional pharmaceutical compositions of modafinil.

Claims

1. A pharmaceutical composition in unit dose form, wherein upon administration to a patient, the composition releases two or more amounts of a modafinil compound, comprising:

a) a core particle comprising an effective amount of a modafinil compound;

b) a first membrane comprising a water-insoluble polymer applied in at least 2 circumferential bands;

c) a second membrane comprising an enteric polymer;

wherein the core particle is coated with the first and second membranes to form an active drug particle; and

d) an immediate release formulation of a modafinil compound;

wherein no substantial release of the modafinil compound from the active drug particle occurs until about three to six hours after administration.

2. The pharmaceutical composition of claim 1 wherein the core particle comprises the modafinil compound and a polymeric binder.

3. The pharmaceutical composition of claim 1 wherein the core particle is prepared by precipitation, granulation and milling, or extrusion/spheronization.

4. The pharmaceutical composition of claim 1 wherein the enteric polymers are each independently selected from the group consisting of esters of cellulose, polyvinyl acetate phthalate, pH sensitive methacrylic-methylmethacrylate copolymers and shellac.

6. The pharmaceutical composition of claim 1 wherein at least one of the membranes further comprises a plasticizer.

7. The pharmaceutical composition of claim 6 wherein the plasticizer is selected from the group consisting of triacetin, tri-butyl citrate, tri-ethyl citrate, acetyl tri-n-butyl citrate, diethyl phthalate, castor oil, dibutyl sebacate, acetylated monoglycerides and mixtures thereof.

8. The pharmaceutical composition of claim 1 wherein the second membrane has sufficient thickness to prevent substantial release of the modafinil compound for a period of three to six hours after oral administration to a patient.

9. The pharmaceutical composition of claim 1 wherein the unit dose form is a capsule.

10. The pharmaceutical composition of claim 9 wherein the capsule is a hard gelatin capsule.

11. The pharmaceutical composition of claim 9 wherein the capsule comprises a single form of the active drug particle such that the composition provides for a time-controlled pulsatile release of the modafinil compound upon oral administration to a patient.

12. The pharmaceutical composition of claim 11 wherein the modafinil compound is released from the active drug particle three to six hours after oral administration to a patient.

13. The pharmaceutical composition of claim 9 wherein the capsule comprises two or more active drug particles with different release times.

14. The pharmaceutical composition of claim 1 wherein the active drug particle comprises a delayed extended release formulation of a modafinil compound.

15. The pharmaceutical composition of claim 14 wherein the amount of modafinil compound in the immediate release formulation is 60 to 90 percent by weight of the immediate release formulation.

16. The pharmaceutical composition of claim 15 wherein the immediate release formulation comprises about 79.9% racemic modafinil, about 9.9% lactose monohydrate, about 5% polyvinylpyrrolidone 90, about 5% crosslinked carboxymethylcellulose sodium, and about 0.5% magnesium stearate by weight.

17. The pharmaceutical composition of claim 1 wherein the blood profile of a patient to whom the composition was administered corresponds substantially to the profile set forth in FIG. 2.

18. The pharmaceutical composition of claim 1, further comprising an effective amount of an antidepressant.

19. The pharmaceutical composition of claim 1, 11, or 14 wherein the modafinil compound is racemic modafinil.

20. The pharmaceutical composition of claim 1, 11, or 14 wherein the modafinil compound is the levorotatory form of modafinil.

21. The pharmaceutical composition of claim 1 or 14, wherein the total amount of modafinil compound contained within the dosage form comprises 10 to 800 mg of racemic modafinil.

22. The pharmaceutical composition of claim 9 wherein the capsule comprises a composite dosage form that provides for a time-controlled pulsatile release of the modafinil compound upon oral administration to a patient.

5. The pharmaceutical composition of claim wherein the water insoluble polymer is selected from the group consisting of ethylcellulose;

polyvinyl acetate;

neutral copolymers based on ethyl acrylate and methylmethacrylate; and

copolymers of acrylic and methacrylic acid esters having quaternary ammonium groups.