LIQUID PHARMACEUTICAL COMPOSITION FOR THE DELIVERY OF ACTIVE INGREDIENTS

• US 20130266652A1
• Filed: 10/18/2011
• Published: 10/10/2013
• Est. Priority Date: 10/20/2010
• Status: Active Grant

• Current Assignee: Novaliq GmbH
• Original Assignee: Novaliq GmbH
• Inventors: Theisinger, Bastian, Theisinger, Sonja, Gnther, Bernhard
• Granted Patent: US 9,757,459 B2
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0046 Ear
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears

Abstract

The invention provides novel pharmaceutical compositions based on semifluorinated alkanes which are useful as carriers for a broad range of active ingredients. Preferred active ingredients include poorly water-soluble and/or hydrolytically sensitive drug substances. The compositions are designed as suspensions and have superior physical properties which make them highly useful as pharmaceutical delivery systems. The compositions may be administered topically into the eye, or injected via the subcutaneous or intramuscular route. The invention further provides kits comprising such compositions.

Claims

1. A pharmaceutical composition in the form of a suspension comprising:

(a) particles of an active ingredient, said ingredient being present in a therapeutically effective amount, and

(b) a liquid vehicle comprising a semifluorinated alkane of the formula RFRH wherein RF is a linear perfluorinated hydrocarbon segment with 3 to 10 carbon atoms, and wherein RH is a linear alkyl group with 3 to 10 carbon atoms.

2. The composition of claim 1, being substantially free of surfactant.

3. The composition of claim 1, wherein the active ingredient is poorly water-soluble and/or sensitive to hydrolytic degradation.

4. The composition of claim 3, wherein the active ingredient exhibits a water solubility of less than about 1 mg per ml, as measured at room temperature and neutral pH.

5. The composition of claim 1, wherein the particles of the active ingredient have a size which is predominantly in the range from about 0.2 μ

m to about 200 μ

m.

6. The composition of claim 5, wherein the particles of the active ingredient have a volume mean diameter as measured by laser diffraction of not more than about 15 μ

m.

7. The composition of claim 1, wherein the semifluorinated alkane is selected from F4H5, F4H6, F6H6 and F6H8.

8. The composition of claim 1, further comprising a non-fluorinated organic liquid.

9. The composition of claim 1, being substantially free of water.

10. The composition of claim 1, wherein the liquid vehicle has a refractive index in the range from 1.29 to 1.35 at 20°

C.

11. A method of treating a disease or condition of a patient in need of such treatment, comprising administering an effective amount of the pharmaceutical composition of claim 1 to the patient.

12. The method of claim 11, wherein the disease or condition to be treated is a disease or condition of the eye, ear, or nose, and the pharmaceutical composition is administered topically to the affected area.

13. The method of claim 11, wherein the pharmaceutical composition is administered parenterally by subcutaneous, dermal, intramuscular, or locoregional injection.

14. A container comprising the composition of claim 11 and a dispensing means adapted for topically administering the composition to the eye of a patient, said dispensing means preferably being adapted to dispense the composition dropwise in volumes of less than about 30 μ

l.

15. The method of claim 12, wherein the disease or condition to be treated is a disease or condition of the eye, the pharmaceutical composition is an ophthalmic composition, and the semifluorinated alkane is selected from F4H5, F4H6, F6H6 and F6H8.

16. The composition of claim 3, wherein the poorly soluble active ingredient is an antibiotic agent and wherein the semifluorinated alkane is selected from F4H5, F4H6, F6H6 and F6H8.

17. The composition of claim 16, wherein the antibiotic agent is selected from ciprofloxacin, levofloxacin, gentamycin, and tobramycin.

18. The composition of claim 16, wherein the particles of the active ingredient have a size which is predominantly in the range from about 0.2 μ

m to about 200 μ

m.

19. The composition of claim 16, comprising not more than about 5 wt.-% surfactant.

20. The composition of claim 16, wherein the composition is water-free.