Pharmaceutical composition comprising cefuroxime axetil

• US 4,865,851 A
• Filed: 05/13/1988
• Issued: 09/12/1989
• Est. Priority Date: 05/14/1987
• Status: Expired due to Term

• Current Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Original Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Inventors: Elliott, Leonard G., James, Michael B.
• Primary Examiner(s): Page, Thurman K.
• Application Number:
  US07/193,784
• Time in Patent Office: 487 Days
• Field of Search: 424/498, 424/493, 424/495, 424/497
• US Class Current: 424/498
• CPC Class Codes: A61K 31/545 Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: , e.g. cephalosporins, cefaclor, or cephalexine
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents

Abstract

Cefuroxime axetil in particulate form is coated with an integral coating of a lipid or mixture of lipids which serves to mask the bitter taste of cefuroxime axetil but disperses or dissolves on contact with gastrointestinal fluid. The resulting particles may be incorporated into pharmaceutical compositions for oral administration, for instance aqueous suspensions.

Claims

1. A composition comprising cefuroxime axetil in particulate form, the particles being provided with integral coatings of a lipid or a mixture of lipids which are insoluble in water and which serve to mask the bitter taste of cefuroxime axetil upon oral administration but which disperse or dissolve on contact with gastro-intestinal fluid.

2. A composition as claimed in claim 1 wherein the lipid or mixture of lipids has a melting point in the range of from 30°

to 80°

C.

3. A composition as claimed in claim 2 wherein the lipid or mixture of lipids has a melting point in the range of from 40°

to 70°

C.

4. A composition as claimed in claim 1 wherein the lipid or mixture of lipids comprises one or more straight chain aliphatic carboxylic acids having from 10 to 30 carbon atoms.

5. A composition as claimed in claim 4 wherein the mixture of lipids comprises a mixture of stearic and palmitic acids in a ratio of from 3:

7 to 7;

3 by weight.

6. A composition as claimed in claim 5 wherein the mixture of stearic and palmitic acids is in a ratio of about 1:

1 by weight.

7. A composition as claimed in claim 1 containing from 5 to 90% by weight of cefuroxime axetil.

8. A composition as claimed in claim 7 containing from 10 to 30% by weight of cefuroxime axetil.

9. A composition as claimed in claim 1 containing amorphous cefuroxime axetil.

10. A composition as claimed in claim 9 wherein the cefuroxime axetil is spray-dried cefuroxime axetil in the form of hollow microspheres.

11. A composition as claimed in claim 1 wherein the coated particles have diameters in the range from 1 to 250 microns.

12. A composition as claimed in claim 1 wherein the coated particles have a mean diameter by volume of less than 100 microns.

13. A process for the preparation of a composition as claimed in claim 1 which comprises dispersing particulate cefuroxime axetil in a molten lipid or mixture of lipids, atomising the dispersion to provide particles having integral coatings of the lipid or mixture of lipids and cooling and collecting the coated particles thereby obtained.

14. A process as claimed in claim 13 wherein the lipid or mixture of lipids has a melting point in the range of from 30°

to 80°

C.

15. A process as claimed in claim 14 wherein the lipid or mixture of lipids has a melting point in the range of from 40°

to 70°

C.

16. A process as claimed in claim 13 wherein the lipid or mixture of lipids comprises one or more straight chain aliphatic carboxylic acids having from 10 to 30 carbon atoms.

17. A process as claimed in claim 16 wherein the mixture of lipids comprises a mixture of stearic and palmitic acids in a ratio of from 3:

7 to 7;

3 by weight.

18. A process as claimed in claim 17 wherein the mixture of stearic and palmitic acids is in a ratio of about 1:

1 by weight.

19. A process as claimed in claim 13 wherein the dispersion is atomised by a pneumatic nozzle atomiser.

20. A process as claimed in claim 19 wherein the atomiser is an internal mixing two-fluid nozzle atomiser.

21. A process as claimed in claim 19 wherein the molten dispersion is atomised at a temperature which is in the range of 10°

to 20°

C. above the melting point of the lipid or mixture of lipids used.

22. A process as claimed in claim 19 wherein the particulate cefuroxime axetil prior to coating has a mean particle diameter by volume in the range of from 5 to 20 microns.

23. A process as claimed in claim 19 wherein the amounts of particulate cefuroxime axetil and lipid or lipid mixture used are such as to provide coated particles containing from 5 to 50% by weight of cefuroxime axetil.

24. A process as claimed in claim 23 wherein the amounts of particulate cefuroxime axetil and lipid or lipid mixture used are such as to provide coated particles containing from 5 to 30% by weight of cefuroxime axetil.

25. A process as claimed in claim 19 wherein the dispersion is atomised to provide coated particles having diameters in the range from 1 to 250 microns.

26. A process as claimed in claim 19 wherein the dispersion is atomised to provide coated particles having a mean diameter by volume of less than 100 microns.

27. A process as claimed in claim 26 wherein the dispersion is atomised to provide coated particles having a mean diameter by volume of from 20 to 100 microns.

28. A process as claimed in claim 27 wherein the dispersion is atomised to provide coated particles having a mean diameter by volume of from 30 to 60 microns.

29. A pharmaceutical composition for oral administration comprising a composition as claimed in claim 1 together with one or more pharmaceutical carriers or excipients.

30. A pharmaceutical composition as claimed in claim 29 in the form of granules.

31. A pharmaceutical composition as claimed in claim 29 in the form of an aqueous suspension.

32. A pharmaceutical composition as claimed in claim 31 containing an orally acceptable solute serving to assist in maintaining the taste-masking properties of the lipid coating.

33. A pharmaceutical composition as claimed in claim 32 wherein the solute is sugar in the concentration range 50 to 85 weight percent.