Antifungal solutions

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

Reexamination Certificate

active

06340698

ABSTRACT:

BACKGROUND OF THE INVENTION
Itraconazole and saperconazole are compounds useful for treating fungal infections in mammals. They may be administered topically, parenterally or orally.
Itraconazole and saperconazole are both particularly insoluble in water. This makes it difficult to formulate itraconazole or saperconazole into aqueous solutions, particularly solutions that are suitable for oral administration.
A solution for oral administration comprising itraconazole is sold in the United States and elsewhere under the tradename Sporanox®. The strength of the solution is 10 mg itraconazole per mL, and the inactive ingredients in addition to water are hydroxypropyl-&bgr;-cyclodextrin, propylene glycol, sorbitol hydrochloric acid, sodium hydroxide, sodium saccharin, and flavours.
The purpose of the hydroxypropyl-&bgr;-cyclodextrin is to improve the aqueous solubility of itraconazole by forming an inclusion complex. This use of cyclodextrin derivatives for solubilizing drugs such as itraconazole and saperconazole is disclosed in U.S. Pat. Nos. 4,727,064 and 5,707,975.
While the use of cyclodextrin derivatives enables production of an oral solution comprising itraconazole or saperconazole, the need to use a cyclodextrin derivative increases the complexity of manufacture of the oral solution and also the cost.
The object of the present invention is thus to enable an oral solution comprising itraconazole or saperconazole, without the use of acyclodextrin derivative to complex the itraconazole or saperconazole.
DESCRIPTION OF THE INVENTION
In this specification and claims, “free itraconazole” and “free saperconazole” will be understood to mean itraconazole and saperconazole not solubilized by complexation with a cyclodextrin derivative.
Although itraconazole and saperconazole are practically insoluble in water, they are soluble in strong acids.
For example, 1 g of free itraconazole can be dissolved in about 3 g of glacial acetic acid or about 3 to 4 g of concentrated hydrochloric acid (i.e. 36-38% HCl in water).
However, strongly acidic solutions are unsuitable for oral administration, and if a solution of itraconazole or saperconazole in strong acid is diluted with water to weaken the acid, the itraconazole or saperconazole precipitates.
It has been found that this problem can be overcome (i.e. the precipitation prevented) by diluting the solution with an alcoholic co-solvent, instead of or in addition to water. Preferred alcoholic co-solvents are propylene glycol, ethanol and glycerol. Most preferred is propylene glycol.
Compositions within the scope of the present invention will thus be solutions in which free itraconazole or free saperconazole is dissolved in a solvent system comprising an acid, and an alcoholic co-solvent. The solvent system will preferably also comprise water. The alcoholic co-solvent will preferably be selected from propylene glycol, ethanol and glycerol, and will most preferably be propylene glycol. It will be understood that a mixture of two or more alcoholic co-solvents may be used instead of one alone.
The concentration of the itraconazole or saperconazole in the solution will preferably be about 10 mg per mL.
The acid will preferably be selected from hydrochloric acid, sulfuric acid and acetic acid, and will most preferably be hydrochloric acid.
The concentration of the alcoholic co-solvent in the solution will be preferably from about 100 to about 800 mg per mL, more preferably from about 200 to about 700 mg per mL, even more preferably from about 300 to about 600 mg per mL, and most preferably from about 400 to about 500 mg per mL.
The pH of solution will be preferably from about 1 to about 4, more preferably from about 1 to about 3, and most preferably from about 1 to about 2.
The solution will optionally contain ingredients in addition to the itraconazole or saperconazole, acid, alcoholic co-solvent, and water.
For example, the solution will preferably contain either sorbitol or sucrose as a sweetener and thickener.
The solution may also contain an artificial sweetener such as, for example, saccharin or saccharin sodium.
The solution will preferably also contain one or more flavouring ingredients, such as, for example, cherry flavour.


REFERENCES:
patent: 4727064 (1988-02-01), Pitha
patent: 5707975 (1998-01-01), Francois et al.
patent: 5750147 (1998-05-01), Kantor
patent: 6100285 (2000-08-01), Kantor
patent: 6143794 (2000-11-01), Chaudhuri et al.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Antifungal solutions does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Antifungal solutions, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antifungal solutions will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-2847743

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.