Controlled release compositions of agents that reduce circulating levels of platelets and methods therefor
AssigneeBioVascular, Inc.
InventorsPaul F. Glidden, Alison J. Pilgrim, Stephen R. Hanson
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Abstract
Provided are prophylactic and therapeutic methods of treatment of subjects for the purpose of inhibiting vaso-occlusive events, including embolism, by administering agents, including anagrelide and anagrelide derivatives, which reduce the number of circulating platelets to low normal or to below normal levels. Methods and pharmaceutical preparations comprising such agents are provided.
Claims43
A pharmaceutical composition in unit dosage form, comprising:
- a solid support core of a substantially water soluble, swellable or insoluble material, wherein the solid support is from 85-95% by weight of the composition;
- a substrate layer comprising a binder and microparticles of anagrelide hydrochloride monohydrate in hydrated crystal form, in an amount that is equivalent to from 50 μg to 10 mg of anagrelide free base, wherein at least 90% of the microparticles are 25 microns or less and the binder is present at a weight of 0.1-5% by weight of the composition;
- a release control component comprising a water insoluble polymer and a plasticizer, wherein the release control component is present at about 1-10% by weight of the composition;
- and
- a seal coat layer comprising a substantially water-soluble polymer, wherein the seal coat is present at about 1-5% by weight of the composition and is disposed between the substrate layer and the release control component and reduces chemical interaction between the anagrelide hydrochloride monohydrate in the substrate layer and the plasticizer in the release control component,
- wherein the hydrated crystal form of the anagrelide hydrochloride monohydrate in the composition has a shelf stability of at least three months under normal storage conditions.
A composition in unit dosage form, comprising:
- a solid support core of a nonpareil sugar spheres;
- a substrate layer comprising microparticles of anagrelide hydrochloride monohydrate in hydrated crystal form in an amount equivalent to about 0.1 to 1.0 mg of anagrelide free base, and hydroxypropyl methyl cellulose as a binder;
- a seal coat layer comprising hydroxypropyl methylcellulose;
- and
- a release control component for controlled release of the anagrelide hydrochloride comprising ethyl cellulose, hydroxypropyl methylcellulose and triethylacetate;
- wherein the seal coat is disposed between the substrate layer and the release control component, and reduces chemical interaction between the anagrelide hydrochloride monohydrate in the substrate layer and the triethylacetate in the release control component, and
- wherein the hydrated crystal form of the anagrelide hydrochloride monohydrate in the composition has a shelf stability of at least three months under normal storage conditions.
The composition of 21, wherein the ethylcellulose is present in an amount to yield a ratio of ethylcellulose to the hydroxypropyl methylcellulose of 3:1 in the release control component.
The composition of 21, wherein the release control component is about 1% to at or about 5% by weight of the composition.
Dependencies are inferred from the claim text.