Method of preparing a pharmaceutical composition and pharmaceutical compositions obtainable thereby

• US 20070104791A1
• Filed: 12/20/2005
• Published: 05/10/2007
• Est. Priority Date: 10/24/2005
• Status: Abandoned Application

• Current Assignee: Fortune Apex Development Limited
• Original Assignee: Fortune Apex Development Limited
• Inventors: Tzachev, Christo, Popov, Todor
• Application Number:
  US11/312,887
• Publication Number:
  US 20070104791A1
• Time in Patent Office: Days
• US Class Current: 424/488
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants

Abstract

An aqueous pharmaceutical composition comprising: a) 0.005 to 10% by wt of one or more water-soluble pharmaceutically active ingredients or pharmaceutically acceptable salts thereof; b) from 0.01 to 10% by wt hydroxypropyl methyl cellulose having a viscosity of from 2500 to 5500 cps (mPa·s); and c) a buffer for maintaining the pH of the aqueous pharmaceutical composition from 5 to 7; can be prepared by a method which comprises: i) dissolving the above components in water to form an aqueous solution, and ii) filtering the aqueous solution formed in i) through a sieve having a mesh size from ≧1 micron but ≦10 microns. The compositions obtainable by this method are capable of demonstrating improved mucoadhesive consistency and stability.

Claims

1. A method for the preparation of an aqueous pharmaceutical composition comprising:

a) 0.005 to 10% by wt of one or more water-soluble pharmaceutically active ingredients or pharmaceutically acceptable salts thereof;

b) from 0.01 to 10% by wt hydroxypropyl methyl cellulose, having a viscosity of from 2500 to 5500 cps (mPa·

s); and

c) a buffer for maintaining the pH of the aqueous pharmaceutical composition from 5 to 7;

wherein the method comprises;

i) dissolving the above components in water to form an aqueous solution; and

ii) filtering the aqueous solution formed in i) through a sieve to form an aqueous pharmaceutical composition;

characterised in that;

the sieve through which the aqueous solution is filtered has a mesh size from ≧

1 micron but ≦

10 microns.

2. A method as claimed in claim 1, wherein the one or more water-soluble pharmaceutically active ingredients or pharmaceutically acceptable salts thereof is selected from vascoconstrictors, antiallergic agents, antiemetics, bronchodilators, antiseptics, local anesthetics, cytostatics, analgesics (narcotic and non-narcotic), steroidal and non-steroidal anti-inflammatories, topical antibiotics, antiparasitics, antibacterials, anticonvulsants, antispasmodics and anticholinergics, antifungals, antivirals, antidiabetics, antimigraines, hormones, sedatives, antianaphylactics, beta-adrenoceptor agonists, diagnostic drugs, and vaccines.

3. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble vasoconstrictor selected from xylometazoline, indanazoline, metizoline, naphazoline, fenoxazoline, oxymetazoline, tetrahydrozoline, tramazoline, tymazoline, phenylephrine, ephedrine and epinephrine.

4. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antiallergic agent selected from (1) cromoglycic acid, or (2) H1 receptor antagonists.

5. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble steroidal or non-steroidal anti-inflammatory selected from corticosteroids, diclofenac and celecoxib.

6. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antiemetic selected from metoclopramide, ondansetron, granisetron, dronabinol, prochloperazine and chlorpromazine.

7. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble narcotic and non-narcotic analgesic selected from morphine, hydromorphine, pentazocine, and acetaminophen.

8. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble anesthetic selected from lidocaine, pramoxine and benzocaine.

9. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble topical antibiotic selected from neomycin and bacitracin.

10. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antiparasitic selected from metronidazole and quinolines.

11. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antibacterial selected from tetracycline, erythromycin, quinolone antibacterials, and azithromycin.

12. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble anticonvulsant selected from phenyloin, gabapentin, phenobarbital and carbamazepine.

13. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antispasmodic or anticholinergic selected from atropine and scopolamine.

14. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antifungal selected from miconazole, econazole and terconazole.

15. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antiviral include acyclovir and behenyl alcohol.

16. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antidiabetic selected from glipizide and glyburide.

17. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antimigraine selected from sumatriptan and ergotamine.

18. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble hormones selected from insulin, steroidal hormones, calcitonin, melatonin and tissue growth factors.

19. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble sedatives selected from barbiturates and benzodiazepines.

20. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble antianaphylactic selected from adrenaline and epinephrine.

21. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble beta-adrenoceptor agonists selected from ephedrine hydrochloride, salbutamol/albuterol, fenoterol, clenbuterol, salmeterol and formoterol.

22. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble diagnostic drug selected from phenolsulfonphthalein, Dye T-1824, vital dyes, potassium ferrocyanide, secretin, pentagastrin and cerulean.

23. A method as claimed in claim 1, wherein the pharmaceutically active ingredient is a water-soluble vaccine.

24. A method as claimed in claim 1, wherein the water-soluble pharmaceutically active ingredient is selected from one or more of xylometazoline, indanazoline, metizoline, naphazoline, fenoxazoline, oxymetazoline, tetrahydrozoline, tramazoline, tymazoline, phenylephrine, ephedrine, epinephrine, cromoglycic acid, dimethindene, acrivastine, azelastine, brompheniramine, chlorpheniramine, dexchlorpheniramine, triprolidine, bromodiphenhydramine, clemastine, phenyltoloxamine, piprinhydrinate, pyrilamine, tripelennamine, cetirizine, levocetirizine, hydroxyzine, methdilazine, promethazine, trimeprazine, azatadine, cyproheptadine, loratadine, desloratadine, astemizole, diphenhydramine, levocabastine orterfenadine, beclomethasone, fluticasone, diclofenac, celecoxib, metoclopramide, ondansetron, granisetron, dronabinol, prochloperazine, chlorpromazine, morphine, hydromorphine, pentazocine, acetaminophen, lidocaine, pramoxine, benzocaine, neomycin, bacitracin, metronidazole, quinolines, tetracycline, erythromycin, quinolone antibacterials, azithromycin, phenyloin, gabapentin, phenobarbital, carbamazepine, atropine, scopolamine, miconazole, econazole, terconazole, acyclovir, behenyl alcohol, glipizide, glyburide, sumatriptan, ergotamine, insulin, steroidal harmones, calcitonin, melatonin, tissue growth factors, barbiturates, benzodiazepines, adrenaline, epinephrine, salbutamol/albuterol, fenoterol, clenbuterol, salmeterol, formoterol, phenolsulfonphthalein, Dye T-1824, vital dyes, potassium ferrocyanide, secretin, pentagastrin, cerulean, allergens for immunotherapy and oral bacterial vaccines used as immunomodulators, or a pharmaceutically acceptable salt thereof.

33. A method as claimed in claim 1, wherein the active ingredient comprises a mixture of more than one water soluble active ingredient.

34. A method as claimed in claim 1, wherein the pharmaceutical composition includes disodium phosphate dodecahydrate and/or sodium dihydrogen phosphate dihydrate.

35. A method as claimed in claim 1, wherein the pharmaceutical composition includes a chelating agent, such as the disodium salt of ethylene diamine tetraacetic acid.

36. A method as claimed in claim 1, wherein the pharmaceutical composition includes an isotonicity regulator, such as sodium chloride.

37. A method as claimed in claim 1, wherein the pharmaceutical composition is free of a preservative which is not also a chelating agent.

38. A method as claimed in claim 1, wherein the hydroxypropyl methyl cellulose has a viscosity of from 2500 to 5500 cps (mPa·

s), preferably more than 3000 to less than 5000 cps (mPa·

s), more preferably from 3200 to 4800 cps (mPa·

s).

39. An aqueous pharmaceutical composition comprising:

a) 0.005 to 10% by wt, preferably 0.01 to 5% by wt, more preferably 0.25 to 2.5 wt %, most preferably 0.25 to 1.5% by wt of one or more water-soluble pharmaceutically active ingredients or pharmaceutically acceptable salt thereof;

b) from 0.01 to 10% by wt, preferably from 0.05 to 5% by wt, more preferably 0.1 to 5% by wt, most preferably 0.1 to 2% by wt, hydroxypropyl cellulose having a viscosity of from 2500 to 5500 cps (mPa·

s), preferably more than 3000 to less than 5000 cps (mPa·

s), more preferably from 3200 to 4800 cps (mPa·

s), and

c) a buffer for maintaining the pH of the aqueous pharmaceutical composition at from 5 to 7,

wherein the composition is obtainable or obtained by the method claimed in any one of the preceding claims.

25. A method for the preparation of an aqueous nasal pharmaceutical composition comprising:

a) 0.005 to 10% by wt, preferably 0.01 to 5% by wt, more preferably 0.25 to 2.5 wt %, most preferably 0.25 to 1.5% by wt of one or more water-soluble pharmaceutically active ingredients suitable for nasal administration;

b) from 0.01 to 10% by wt, preferably from 0.05 to 5% by wt, more preferably 0.1 to 5% by wt, most preferably 0.1 to 2% by wt, hydroxypropyl methyl cellulose having a viscosity of from 2500 to 5500 cps (mPa·

s), preferably more than 3000 to less than 5000 cps (mPa·

s), more preferably from 3200 to 4800 cps (mPa·

s), and

c) a buffer for maintaining the pH of the aqueous pharmaceutical composition at from 5 to 7,

wherein the method comprises;

i) dissolving the above components in water to form an aqueous solution, and

ii) filtering the aqueous solution formed in i) through a sieve to form an aqueous nasal pharmaceutical composition;

characterised in the that the sieve through which the aqueous solution is filtered has a mesh size from ≧

1 micron but ≦

10 microns, preferably from 1.5 to 5 microns, most preferably 2 to 4 microns, e.g. 3 microns.

26. A method as claimed in claim 25, wherein the water soluble pharmaceutically active ingredient is selected from vascoconstrictors, antiallergic agents, antiemetics, bronchodilators, antiseptics, anesthetics, cytostatics and corticosteroids.

27. A method as claimed in claim 26, wherein the water-soluble vasoconstrictor is selected from xylometazoline e.g. xylometazoline hydrochloride, indanazoline, metizoline, naphazoline e.g. naphazoline hydrochloride, fenoxazoline e.g. fenoxazoline hydrochloride, oxymetazoline e.g. oxymetazoline hydrochloride, tetrahydrozoline, tramazoline, tymazoline, phenylephrine e.g. phenylephrine hydrochloride, ephedrine e.g. d-pseudoephedrine hydrochloride, or epinephrine.

28. A method as claimed in claim 25, wherein the water-soluble active ingredient is selected from xylometazoline, e.g. xylometazoline hydrochloride, oxymetazoline, e.g. oxymetazoline hydrochloride, and metoclopramide, e.g. metoclopramide hydrochloride.

29. A method as claimed in claim 28, wherein the water soluble active ingredient is xylometazoline e.g. xylometazoline hydrochloride.

30. A method as claimed in claim 26, wherein the water soluble antiallergic agent is selected from (1) cromoglycic acid or a nasally acceptable salt thereof, e.g. disodium cromoglycate), or (2) H1 receptor antagonists, such as dimethindene or a nasally acceptable salt thereof, e.g. dimethindene maleate, acrivastine, brompheniramine, chlorpheniramine, dexchlorpheniramine, triprolidine, bromodiphenhydramine, clemastine, phenyltoloxamine, piprinhydrinate, pyrilamine, tripelennamine, azelastine, cetirizine, levocetirizine, hydroxyzine, methdilazine, promethazine, trimeprazine, azatadine, cyproheptadine, loratadine, desloratadine, astemizole, diphenhydramine, levocabastine orterfenadine.

31. A method as claimed in claim 26, wherein the water soluble corticosteroid is selected from beclomethasone e.g. beclomethasone dipropionate, and fluticasone e.g. fluticasone propionate.

32. A method as claimed in claim 26, wherein the water-soluble antiemetic is metoclopramide e.g. metoclopramide hydrochloride

40. A method as claimed in claim 25, wherein the active ingredient comprises a mixture of more than one water soluble active ingredient.

41. A method as claimed in claim 25, wherein the pharmaceutical composition includes disodium phosphate dodecahydrate and/or sodium dihydrogen phosphate dihydrate.

42. A method as claimed in claim 25, wherein the pharmaceutical composition includes a chelating agent, such as the disodium salt of ethylene diamine tetraacetic acid.

43. A method as claimed in claim 25, wherein the pharmaceutical composition includes an isotonicity regulator, such as sodium chloride.

44. A method as claimed in claim 25, wherein the pharmaceutical composition is free of a preservative which is not also a chelating agent.

45. A method as claimed in claim 25, wherein the hydroxypropyl methyl cellulose has a viscosity of from 2500 to 5500 cps (mPa·

s), preferably more than 3000 to less than 5000 cps (mPa·

s), more preferably from 3200 to 4800 cps (mPa·

s).