Pharmaceutical compositions containing drugs which are instable or sparingly soluble in water and methods for their preparation
AssigneeJanssen Pharmaceutica NV
InventorsBernd W. Müller, Ulrich Brauns
Life of this patent
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Abstract
Pharmaceutical compositions comprising inclusion compounds of sparingly water-soluble or water-instable drugs with β-cyclodextrin ethers or β-cyclodextrin esters and process for the preparation thereof.
Claims35
Pharmaceutical composition comprising an inclusion compound of (i) a drug capable of fitting into the cavity of the cyclodextrin ring system which is instable or only sparingly soluble in water with (ii) a partially etherified β-cyclodextrin of the formula:
- (β-CD)—OR (I)
- wherein the residues R are hydroxyalkyl groups and part of said residues R may optionally be alkyl groups, the βcyclodextrin ether having a water solubility of greater than 1.8 g in 100 ml water, wherein said composition has considerably increased water solubility and stability relative to said drugs, with very low toxicity.
Pharmaceutical composition comprising an inclusion compound of (i) a drug which is instable or only sparingly soluble in water and which is capable of fitting into the cavity of the β-cyclodextrin ring system and
- (ii) a β-cyclodextrin derivative of the formula:
- (β-CD)—OR
- wherein β-CD represents β-cyclodextrin and the residue(s) R is selected from hydroxyethyl, hydroxypropyl, dihydroxypropyl, methyl, and ethyl or mixtures thereof;
- provided that;
- (a) the molar substitution by hydroxyethyl, hydroxypropyl, and dihydroxypropyl is from 0.05 to 10, and
- (b) the degree of substitution by methyl and ethyl is from 0 to 2.0 and
- (c) the molar ratio of said drug to said β-cyclodextrin derivative is from 1:6 to 4:1, and
- (d) the water solubility of said β-cyclodextrin derivative is greater than 1.8 g in 100 ml of water.
A method of producing a stabilizing amorphous complex of a drug and mixture of beta-cyclodextrin derivatives comprising the steps of:
- (1) dissolving the intrinsically amorphous mixture of beta-cyclodextrin derivatives which are water soluble and capable of forming inclusion complexes with drugs in water, and
- (2) solubilizing sparingly water-soluble drugs into the aqueous media to form a solution and form a solubilized drug/cyclodextrin complex.
A composition of matter which contains a water-soluble amorphous complex of beta-cyclodextrin derivatives and a drug.
A composition of matter in solid form comprising progesterone as an inclusion complex with hydroxypropyl-beta-cyclodextrin adapted for administration by the oral route.
Pharmaceutical composition comprising an inclusion compound of (i) a drug capable of fitting into the cavity of the β-cyclodextrin ring system which is instable or only sparingly soluble in water and (ii) a partially etherified β-cyclodextrin derivative of the formula:
- (β-CD)—OR
- wherein β-CD represents β-cyclodextrin and the residue R is a hydroxyalkyl group and the β-cyclodextrin has a molar substitution by hydroxyalkyl of about 0.25 to about 1.
Pharmaceutical composition comprising an inclusion compound of (i) a drug capable of fitting into the cavity of the β-cyclodextrin ring system which is instable or only sparingly soluble in water and (ii) a partially etherified β-cyclodextrin derivative of the formula:
- (β-CD)—OR
- wherein β-CD represents β-cyclodextrin and the residues R are in part hydroxyalkyl groups and in part alkyl groups, said alkyl groups being present up to a degree of substitution between about 0.05 to 2.
Dependencies are inferred from the claim text.