Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-10-10
2001-12-18
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S780000, C514S782000, C514S235500, C514S947000, C424S675000, C424S678000
Reexamination Certificate
active
06331540
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to pharmaceutical compositions. In particular, this invention relates to pharmaceutical compositions formulated so that fluoroquinolone antibiotic drugs and xanthan gum are compatible.
2. Description of Related Art
Xanthan gum is a polysaccharide known to be useful in ophthalmic compositions as a viscosity-enhancing agent. U.S. Pat. No. 4,136,177 discloses ophthalmic compositions containing an ophthalmic drug and from about 0.01 to 2.5% (w/v) of xanthan gum. The '177 patent teaches that if the concentration of xanthan gum is from about 0.02 to about 1.0% (w/v), the composition is suitable for “dropwise” ophthalmic applications. In contrast, at concentrations of xanthan gum above about 1.0% and up to about 2.5% (w/v), “a gel-like consistency is attained.” Thus, the '177 patent discloses compositions that are formulated to be either non-gelled liquids or gels before instillation in the eye. The '177 patent does not describe any xanthan gum-containing compositions as capable of being administered as a liquid and gelling upon contact with the eye. According to the '177 patent, any ophthalmic drug can be added to the xanthan gum-containing compositions, but the '177 patent does not include a fluoroquinolone antibiotic drug when it lists suitable antibacterial drugs (see Col. 3, lines 54 -58).
WO 99/51273 discloses gel-forming compositions containing xanthan gum where the xanthan gum has an initial bound acetate content of at least about 4% and an initial bound pyruvate content of at least about 2.5%. The entire contents of WO 99/51273 are hereby incorporated by reference.
Ciprofloxacin is an antibiotic drug known to be useful in pharmaceutical compositions. Because of solubility limitations, topically administrable aqueous compositions containing 0.3% (w/w) ciprofloxacin are generally formulated at low pH (e.g., pH 4.5) in order to avoid ciprofloxacin precipitating out of the composition. U.S. Pat. No. 5,679,336 discloses topically administrable pharmaceutical compositions formulated as solutions at or near physiological pH using polystyrene sulfonic acid.
Adding 0.3% (w/w) ciprofloxacin to a simple aqueous xanthan gum-containing composition, even at a pH of 4.5, causes a precipitate to form between ciprofloxacin and xanthan gum.
SUMMARY OF THE INVENTION
The present invention is directed toward a method of making fluoroquinolone antibiotic drugs and xanthan gum compatible in aqueous pharmaceutical compositions. According to the present method, a calcium salt is added to the composition in an amount sufficient to make the fluoroquinolone drug compatible with xanthan gum. The present invention is also directed toward compositions containing a fluoroquinolone drug, xanthan gum and a calcium salt in an amount sufficient to make the fluoroquinolone drug and xanthan gum compatible. The methods and compositions of the present invention include a minimum of 0.15 wt. % of calcium salt such that the formulations have a turbidity rating of ≦40 NTU (nephelos turbidity units) at room temperature.
Among other factors, the present invention is based upon the finding that, unlike salts of monovalent cations or multivalent anions, calcium salts are particularly effective in making ciprofloxacin and xanthan gum compatible in pharmaceutical compositions.
DETAILED DESCRIPTION OF THE INVENTION
Unless otherwise indicated, all ingredient concentrations are listed as % (w/w).
Xanthan gum is a well-known polysaccharide that is commercially available from a variety of sources. The amount of xanthan gum contained in the compositions of the present invention will depend upon the properties desired for the final composition and the identity and concentration of other ingredients in the composition, but will generally range from about 0.4 to about 0.8%, preferably 0.5 -0.7%.
Xanthan gum is generally available in at least two grades from some commercial suppliers, a food or industrial grade and a pharmaceutical grade. It is preferable to polish filter even pharmaceutical grade materials so that the finished pharmaceutical product will have increased clarity. As one skilled in the art appreciates, the appropriate filter size for polish filtration depends upon the size of the undesired impurities contained in raw material. For example, in the case of a solution composition, it has been found that the Rhodigel Clear grade of xanthan gum from Rhone- Poulenc Inc. should be filtered through a 0.45 &mgr;m filter in order to remove cell debris and impurities. Multiple stages of filters can be used to increase the overall efficiency of the polish filtration process.
Although the amount of the fluoroquinolone drug included in the compositions of the present invention will be whatever amount is therapeutically effective and will depend upon a number of factors, including the identity and potency of the chosen drug, the total concentration of drug will generally be about 1% or less. A preferred fluoroquinolone antibiotic drug is ciprofloxacin. In topically administrable ophthalmic compositions, the preferred concentration of ciprofloxacin will range from 0.2 -0.4%.
In addition to xanthan gum and a fluoroquinolone antibiotic drug, the compositions of the present invention include a water-soluble calcium salt in an amount sufficient to make the xanthan gum and the fluoroquinolone drug compatible. The necessary amount of calcium salt will depend upon the concentration of xanthan gum, the identity and concentration of the fluoroquinolone drug and the desired clarity of the final formulation. In general, however, the calcium salt concentration should be sufficient to give the final formulation a turbidity (nephelos) rating of ≦40 NTU at room temperature. The calcium salt concentration is preferably ≧0.15%. Suitable water-soluble calcium salts include calcium chloride, calcium lactate; calcium acetate; calcium propionate and calcium ascorbate. The most preferred calcium salt is calcium chloride.
The compositions of the present invention may include other components. For example, the compositions may include a second active agent (not limited to anti-infective agents). The compositions may also contain one or more excipients including, but not limited to, pharmaceutically acceptable buffering agents, preservatives (including preservative adjuncts), tonicity-adjusting agents including salts containing monovalent cations, surfactants, solubilizing agents, stabilizing agents, comfort-enhancing agents, emollients, pH-adjusting agents and/or lubricants.
REFERENCES:
patent: 3700451 (1972-10-01), Sullivan, Jr.
patent: 3784712 (1974-01-01), Glicksman et al.
patent: 3944427 (1976-03-01), Sullivan, Jr.
patent: 4135979 (1979-01-01), Corley et al.
patent: 4136173 (1979-01-01), Pramoda et al.
patent: 4136177 (1979-01-01), Lin et al.
patent: 4136178 (1979-01-01), Lin et al.
patent: 4638059 (1987-01-01), Sutherland
patent: 4647470 (1987-03-01), Sanderson et al.
patent: 4661475 (1987-04-01), Bayerlein et al.
patent: 4708861 (1987-11-01), Popescu et al.
patent: 4717713 (1988-01-01), Zatz et al.
patent: 4775632 (1988-10-01), Gozard et al.
patent: 4861760 (1989-08-01), Mazuel et al.
patent: 4996197 (1991-02-01), Mazuel
patent: 5192535 (1993-03-01), Davis et al.
patent: 5212162 (1993-05-01), Missel et al.
patent: 5234957 (1993-08-01), Mantelle
patent: 5318780 (1994-06-01), Viegas et al.
patent: 5403841 (1995-04-01), Lang et al.
patent: 5422116 (1995-06-01), Yen et al.
patent: 5446070 (1995-08-01), Mantelle
patent: 5461081 (1995-10-01), Ali et al.
patent: 5462749 (1995-10-01), Rencher
patent: 5473062 (1995-12-01), Haze et al.
patent: 5493015 (1996-02-01), Murofushi et al.
patent: 5587175 (1996-12-01), Viegas et al.
patent: 5610184 (1997-03-01), Shahinian, Jr.
patent: 5618800 (1997-04-01), Kabra et al.
patent: 5679336 (1997-10-01), Ali et al.
patent: 5736161 (1998-04-01), Garces et al.
patent: 5759563 (1998-06-01), Yewey et al.
patent: 5888493 (1999-03-01), Sawaya
patent: 6153208 (2000-11-01), McAtee et al.
patent: 6166012 (2000-12-0
Alcon Universal Ltd.
Fay Zohreh
Kwon Brian-Yong
Ryan Patrick M.
LandOfFree
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