Methods for treating early morning pathologies

• US RE39,239 E1
• Filed: 09/17/2002
• Issued: 08/15/2006
• Est. Priority Date: 01/29/1997
• Status: Expired due to Term

• Current Assignee: Polichem, SA (Grupo Corporativo Landon SL)
• Original Assignee: Polichem, SA (Grupo Corporativo Landon SL)
• Inventors: Busetti, Cesare, Crimella, Tiziano
• Primary Examiner(s): Dodson, Shelley A.
• Assistant Examiner(s): George, Konata M.
• Application Number:
  US10/246,183
• Time in Patent Office: 1,428 Days
• Field of Search: 424/400, 424/458, 424/480, 424/482, 514/313, 514/453, 514/468, 514/510
• US Class Current: 424/480
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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: 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

Abstract

The present invention provides methods of treating early morning pathologies using a time-specific controlled release dosage formulation which is administered prior to sleep, and which permits or achieves delivery of a pharmaceutically active agent effective for the treatment of the specific early morning pathology to be treated, at about the time of awakening. The time-specific controlled release dosage formulation comprises (1) a core including the pharmaceutically active agent(s) effective for the treatment of the early morning pathology, and (2) a swellable polymeric coating layer substantially surrounding the core. The swellable polymeric coating layer delays the release of the pharmaceutically active agent from the core for a predetermined period of time dependent upon the thickness of the swellable polymeric coating layer, to effect delivery of the pharmaceutically active agent at about the time of awakening.

Claims

1. A method for treating an early morning pathology, said method comprising administering to a subject in need of treatment, a time-specific controlled release dosage formulation comprising consisting essentially of (1) a core including at least one pharmaceutically active agent effective for the treatment of said morning pathology, and (2) a an outer swellable and erodible polymeric coating layer substantially surrounding said core;

wherein said formulation is administered prior to sleep, and wherein said swellable polymeric coating layer delays the release of said pharmaceutically active agent from said core for a predetermined period of time dependent upon the thickness of said swellable polymeric coating layer, to permit delivery of said pharmaceutically active agent at about the time of awakening and to treat said early morning pathology.

2. The method according to claim 1, wherein said early morning pathology is asthma and said pharmaceutically active agent is selected from the group consisting of steroids, xanthines, beta-2-agonist bronchodilators, and anti-asthmatic non-steroidal antiinflammatory agents.

3. The method according to claim 2, wherein said pharmaceutically active agent is selected from the group consisting of betamethasone, dexamethasone, methylprednisolone, prednisolone, prednisone, triamcinolone, theophylline, aminophylline, doxophylline, salbutamol, fenoterol, clenbuterol, bambuterol, and sodium cromoglycate.

4. The method according to claim 1, wherein said early morning pathology is angina and said pharmaceutically active agent is selected from the group consisting of antiangina agents.

5. The method according to claim 4, wherein said pharmaceutically active agent is selected from the group consisting of isosorbide mononitrate, and isosorbide dinitrate.

6. The method according to claim 1, wherein said early morning pathology is arthritis and said pharmaceutically active agent is an antiarthritis non-steroidal antiinflammatory agents.

7. The method according to claim 6, wherein said pharmaceutically active agent is selected from the group consisting of sulfides, mesalamine, salazopyrin, diclofenac, pharmaceutically acceptable salts of diclofenac, nimesulide, ketoprofen, and piroxicam.

8. The method according to claim 1, wherein said early morning pathology is hypertension and said pharmaceutically active agent is selected from the group consisting of calcium antagonists, angiotensin-converting enzyme inhibitors, beta-blockers, centrally active alpha-agonists, and alpha-1-antagonists.

9. The method according to claim 1, wherein said early morning pathology is myocardial or cerebral infarction and said pharmaceutically active agent is selected from the group consisting of anticoagulant agents and antiplatelet agents.

10. The method according to claim 9, wherein said pharmaceutically active agent is selected from the group consisting of warfarin, acetylsalicylic acid, and ticlopidine.

11. The method according to claim 1, wherein said early morning pathology is Parkinson'"'"'s disease or Parkinsonism and said pharmaceutically active agent is selected from the group consisting of dopamine, L-Dopa/Carbidopa, selegiline, dihydroergocryptine, and bromocriptine.

12. The method according to claim 1, wherein said early morning pathology is sleep disorder, and said pharmaceutically active agent is selected from the group consisting of sedatives and ansiolytic agents.

13. The method according to claim 12, wherein said pharmaceutically active agent is a benzodiazepine.

14. The method according to claim 1, wherein said early morning pathology is incontinence, and said pharmaceutically active agent is selected from the group consisting of anticholinergic/antispasmodic agents and vasopressin analogues.

15. The method according to claim 14, wherein said pharmaceutically active agent is selected from the group consisting of flavoxate, oxybutynin, and desmopressine.

16. The method according to claim 1, wherein said formulation is administered orally prior to sleep.

17. The method according to claim 1, wherein said swellable polymeric coating layer comprises a hydrophilic swellable polymer selected from the group consisting of methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, polyvinyolpyrrolidone, polyvinyl alcohol, acrylic acid polymer, methacrylic acid copolymers, ethyl acrylate-methyl methacrylate copolymers, natural rubbers, poloxamers, polysaccharides, and mixtures thereof.

18. The method according to claim 1, wherein said swellable polymeric coating layer is applied to said core by film coating.

19. The method according to claim 1, wherein said swellable polymeric coating layer is applied to said core by alternately (i) wetting said core with a binder solution and (ii) coating said core with powdered polymeric coating particles, a sufficient number of times to produce the desired thickness of swellable polymeric coating layer.

20. The method according to claim 19, wherein said binder solution is selected from the group consisting of polyvinylpyrrolidone, hydroxypropylmethylcellulose, polyvinyl alcohol, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, methacrylic acid copolymers, ethyacrylate-methylmethacrylate copolymers, guar gum, arabic gum, xanthan gum, gelatine, pectin and mixtures thereof;

and said powdered polymeric coating particles comprise a hydrophilic swellable polymer selected from the group consisting of methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, polyvinylolpyrrolidone, polyvinyl alcohol, acrylic acid polymer, methacrylic acid copolymers, ethyl acrylate-methyl methacrylate copolymers, natural rubbers, poloxamers, polysaccharides, and mixtures thereof.

21. The method according to claim 1, wherein said swellable polymeric coating layer comprises hydroxypropylmethylcellulose.

22. The method according to claim 1, wherein said swellable polymeric coating layer comprises a mixture of 1) hydroxypropylmethylcellose having a typical weight percent substitution corresponding to 29% methoxyl and 8% hydroxypropoxyl groups, and a nominal viscosity of 2% water solution at 20°

C. ranging from 3 to 100 mPa.s; and

     2) hydroxypropylmethylcellulose having a typical weight percent substitution corresponding to 22.1% methoxyl and 8.1% hydroxypropoxyl groups, and a nominal viscosity of 2% water solution at 20°

C. ranging from 4,000 to 100,000 mPa.s.

23. The method according to claim 1, wherein said swellable polymeric coating layer is sufficiently thick to achieve a core:

coating layer weight ratio of between about 20;

1 and about 1;

5.

24. The method according to claim 1, wherein said swellable polymeric coating layer is sufficiently thick to achieve a core:

coating layer weight ratio of between about 5;

1 and about 1;

3.

25. The method according to claim 1, wherein said swellable polymeric coating layer is not less than about 50 μ

m thick.

26. The method according to claim 1, wherein said core further comprises a disintegration enhancing agent.

27. The method according to claim 26, wherein said disintegration enhancing agent is selected from the group consisting of citric acid, tartaric acid, fumaric acid, maleic acid, succinic acid, succinic anhydride, maleic anhydride, sodium dihydrogen phosphate, disodium dihydrogen pyrophosphate, sodium dihydrogen citrate, disodium hydrogen citrate, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium sesquicarbonate, glycine sodium carbonate, calcium carbonate, L-lysine carbonate, and arginine carbonate.

28. A method for treating an early morning pathology, said method comprising administering to a subject in need of treatment a time-specific controlled release dosage formulation comprising:

(1) a core including at least one pharmaceutically active agent effective for the treatment of said morning pathology, and

(2) an outer swellable polymeric coating layer substantially surrounding said core;

wherein said formulation is administered prior to sleep, and wherein swelling and erosion of said swellable polymeric coating layer inhibits the release of said pharmaceutically active agent from said core for a predetermined period of time dependent solely upon the thickness of said swellable polymeric coating layer, to permit delivery of said pharmaceutically active agent at about the time of awakening and to treat said early morning pathology.

29. A method for treating an early morning pathology, said method comprising administering to a subject in need of treatment, a time-specific controlled release dosage formulation comprising:

(1) a core including at least one pharmaceutically active agent effective for the treatment of said morning pathology, and

(2) an outer, erodible, swellable polymeric coating layer consisting essentially of at least one swellable polymer substantially surrounding said core;

wherein said formulation is administered prior to sleep, and wherein the time delay before release of said pharmaceutically active agent from said core is solely dependent on the thickness of said swellable polymer, to permit delivery of said pharmaceutically active agent at about the time of awakening and to treat said early morning pathology.

30. A method for treating an early morning pathology, said method comprising administering to a subject in need of treatment a time-specific controlled release dosage formulation comprising:

(1) a core including at least one pharmaceutically active agent effective for the treatment of said morning pathology, and

(2) an outer, erodible swellable polymeric coating layer consisting essentially of at least one swellable polymer substantially surrounding said core;

wherein said formulation is administered prior to sleep, and wherein said swellable polymeric coating layer controls the time delay before release of said pharmaceutically active agent from said core for a predetermined period of time dependent upon the thickness of said swellable polymeric coating layer, to permit delivery of said pharmaceutically active agent at about the time of awakening and to treat said early morning pathology.

31. A method for treating an early morning pathology, said method comprising administering to a subject in need of treatment a time-specific controlled release dosage formulation consisting essentially of:

a first time-specific dosage unit consisting essentially of;

(1) a first core including a pharmaceutically active agent effective for the treatment of said morning pathology and a disintegration enhancing agent, and

(2) a first, outer swellable and erodible polymeric coating layer substantially surrounding said core;

wherein the thickness of said first swellable polymeric coating layer controls the release of said pharmaceutically active agent from said first core for a predetermined period of time dependent upon the thickness of said first swellable polymeric coating layer; and

a second time-specific dosage unit consisting essentially of;

(1) a second core including the pharmaceutically active agent effective for the treatment of said morning pathology, and

(2) a second swellable and erodible polymeric coating layer substantially surrounding said core;

wherein the thickness of said second swellable polymeric coating layer controls the release of said pharmaceutically active agent from said second core for a predetermined period of time dependent upon the thickness of said second swellable polymeric coating layer,

wherein said formulation is administered to the subject prior to sleep, to permit delivery of said pharmaceutically active agent at about the time of awakening, and to treat said early morning pathology.