Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-12-14
2002-02-12
Dees, José G (Department: 1616)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C424S405000, C424S489000, C514S247000, C514S252100, C514S252110, C514S252120, C514S252130, C514S254070, C514S254100, C514S255050, C514S383000, C514S384000, C514S449000, C514S461000, C514S463000, C514S951000
Reexamination Certificate
active
06346533
ABSTRACT:
BACKGROUND OF THE INVENTION
(a) Field of the Invention
The present invention relates to an itraconazole and, more particularly, to an itraconazole exhibiting an improved solubility, a method of preparing the same and a pharmaceutical composition comprising the same.
(b) Description of the Related Art
Because the water-solubility of an azole-type antifungal agent such as itraconazole is low, bioavailability of a drug including the azole-type antifungal agent is low, when the drug is orally administered to a patient. Various studies have been attempted to increase the water solubility and bioavailability of the azole-type antifungal agent. The solubility and bioavailability of the compounds can be increased by complexation with cyclodextrins or derivatives thereof as described in WO 85/02767 and U.S. Pat. No. 4,764,604. WO 94/05263 reports a method of formulating a bead type drug by using a soluble polymer and the itraconazole.
As the azole-type antifungal agent, itraconazole has been widely used. Itraconazole has a molecular formula of C
35
H
38
Cl
2
N
8
O
4
and molecular weight of 705.64. Itraconazole is powder showing light yellow color end insoluble in water (solubility of less than 1 &mgr;g/ml), slightly soluble in alcohol (300 &mgr;g/ml) and soluble in methylene chloride (239 mg/ml). Itraconazole is a weak basic compound (pKa=3.7) and is only ionized at low pH, such as in gastric juice. The log partition coefficient of itraconazole in a system of n-octanol and an aqueous buffer solution of pH 8.1 is 5.66, indicative of very high lipophilicity. This property may influence its plasma protein binding and tissue distribution. Furthermore, it has been known that itraconazole is a broad spectrum antifungal compound developed for oral, parenteral and/or topical use and is disclosed in U.S. Pat. No. 4,267,179.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide itraconazole exhibiting an improved solubility by reducing particle size and changing the crystallinity thereof from crystalline into amorphous.
It is another object to provide a method of preparing the itraconazole by dissolution-induced drying.
It is another object to provide a pharmaceutical composition for oral administrating the itraconazole.
These and other objects may be achieved by itraconazole exhibiting an improved solubility, wherein a particle diameter of the itraconazole is about 0.5 to about 10 &mgr;m and has an amorphous form.
The present invention further includes a method of preparing itraconazole exhibiting the improved solubility. The method includes the steps of dissolving itraconazole in an organic solvent and dissolution-induced drying the mixture.
The present invention further includes a pharmaceutical composition including the itraconazole exhibiting the improved solubility as an active ingredient.
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Chemical Abstracts, vol. 125, No. 26,Dec. 23, 1996, p. 708, column 1, abstract No. 338841t, deChasteigner, S. et al., “Comparative study of the association of itraconazole with colloidal drug carriers” .
Cha Bong-Jin
Kim Su-Eon
Oh Jun-Gyo
Choi Frank
Dees Jose G
Dong-A Pharmaceutical Co., Ltd.
Fish & Richardson P.C.
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