Claims
- 1. A solid dosage form comprising a therapeutic amount of granular particle comprising:a) a solid solution of an amorphous, pharmaceutically active agent and a pharmaceutically acceptable hydrophobic vehicle, wherein said pharmaceutically active agent is normally crystalline and sparingly water-soluble at ambient pressure and temperature; b) a stabilizer comprising a polyethylene glycol, sugars, sorbitol, mannitol, polyvinylpyrrolidone, or one or more cellulose ethers; and c) a disintegrant comprising croscarmellose sodium, sodium starch glycolate, crospovidone, or a cross-linked polyacrylate; wherein said granular particle is made by a process which comprises the steps of: i) heating the hydrophobic vehicle to a temperature to form a molten hydrophobic vehicle and to a temperature at which said pharmaceutically active agent dissolves in the molten hydrophobic vehicle; ii) dissolving said pharmaceutically active agent in the molten hydrophobic vehicle to form a molten solution of said pharmaceutically active agent in said hydrophobic vehicle; then iii) adding a stabilizing amount of said stabilizer to said molten solution; and iv) granulating the molten mixture from step (iii) with a cooled disintegrant and optionally a binder to form said granular particle.
- 2. The solid dosage form according to claim 1 wherein said pharmaceutically active agent is itraconazole.
- 3. The solid dosage form according to claim 2 wherein said hydrophobic vehicle is glyceryl monostearate and is present at about 5% to about 35% by dry weight of said granular particle, said disintegrant is croscarmellose sodium and is present about 3% to about 25% by dry weight of said granular particle, and said stabilizer is hydroxypropylmethylcellulose and is present at about 1% to about 50% by dry weight of said granular particle.
- 4. A dosage form comprising hard gelatin capsules containing a therapeutic amount of the granular particle of claim 1, wherein said therapeutically effective amount, when administered to a patient, is sufficient to function as an antifungal medication.
- 5. A solid dosage form comprising a therapeutic amount of the granular particle of claim 1, wherein said therapeutically effective amount, when administered to a patient, is sufficient to function as an antifungal medication.
- 6. A granular formulation in which the granular particles comprise:a) a solid solution of an amorphous, pharmaceutically active agent and a pharmaceutically acceptable hydrophobic vehicle, wherein said pharmaceutically active agent is normally crystalline and sparingly water-soluble at ambient pressure and temperature; b) a stabilizer comprising a polyethylene glycol, sugars, sorbitol, mannitol, polyvinylpyrrolidone, or one or more cellulose ethers; and c) a disintegrant comprising croscarmellose sodium, sodium starch glycolate, crospovidone, or a cross-linked polyacrylate; wherein said granular particle is made by a process which comprises the steps of: i) heating the hydrophobic vehicle to a temperature to form a molten hydrophobic vehicle and to a temperature at which said pharmaceutically active agent dissolves in the molten hydrophobic vehicle; ii) dissolving said pharmaceutically active agent in the molten hydrophobic vehicle to form a molten solution of said pharmaceutically active agent in said hydrophobic vehicle; then iii) adding a stabilizing amount of said stabilizer to said molten solution; and iv) granulating the molten mixture from step (iii) with a cooled disintegrant and optionally a binder to form said granular particle.
- 7. A granular formulation according to claim 6 wherein said pharmaceutically active agent is itraconazole.
- 8. A granular formulation according to claim 6 said hydrophobic vehicle is glyceryl monostearate and is present at about 5% to about 35% by dry weight of said granular particle, said disintegrant is croscarmellose sodium and is present at about 3% to about 25% by dry weight of said granular particle, and said stabilizer is hydroxypropylmethylcellulose and is present at about 1% to about 50% by dry weight of said granular particle.
- 9. A dosage form comprising hard gelatin capsules containing a therapeutic amount of the granular particle of claim 6, wherein said therapeutically effective amount, when administered to a patient, is sufficient to function as an antifungal medication.
- 10. A solid dosage form comprising a therapeutically effective amount of a granular formulation of claim 6, wherein said therapeutically effective amount, when administered to a patient, is sufficient to function as an antifingal medication.
- 11. A solid dosage form comprising a therapeutic amount of granular particle comprising:a) a solid solution of an amorphous, pharmaceutically active agent and a pharmaceutically acceptable hydrophobic vehicle, wherein said pharmaceutically active agent is itraconazole in an amount of 30% to 35% by dry weight of said granular particle, and wherein said hydrophobic vehicle is glyceryl monostearate in an amount of 5% to 15% by dry weight of said granular particle; b) hydroxypropylmethylcellulose in an amount of 45% to 50% by dry weight of said granular particle; c) croscarmellose sodium in an amount of 10% to 15% by dry weight of said granular particle; wherein said granular particle is made by a process which comprises the steps of: i) heating glyceryl monostearate to a temperature to form a molten glyceryl monostearate and to a temperature at which said itraconozole dissolves in said molten glyceryl monostearate; ii) dissolving said itraconozole in said molten glyceryl monostearate to form a molten solution of itraconozole in glyceryl monostearate; then iii) adding a stabilizing amount of said hydroxypropylmethylcellulose to said molten solution; and iv) granulating the molten mixture from step (iii) with cooled croscarmellose sodium and optionally a binder to form said granular particle.
- 12. A granular formation in which the granular particles comprise:a) a solid solution of an amorphous, pharmaceutically active agent and a pharmaceutically acceptable hydrophobic vehicle, wherein said pharmaceutically active agent is itraconazole in an amount of 30% to 35% by dry weight of said granular particle and a pharmaceutically acceptable hydrophobic vehicle, wherein said hydrophobic vehicle is glyceryl monostearate and is present at 5% to 15% by dry weight of said granular particle; b) hydroxypropylmethycellulose in an amount of 45% to 50% by dry weight of said granular particle; c) croscarmellose sodium in an amount of 10% to about 15% by dry weight of said granular particle; wherein said granular particle is made by a process which comprises the steps of: i) heating said glyceryl monostearate to a temperature to form a molten glyceryl monostearate, and to a temperature at which said itraconozole dissolves in said molten glyceryl monostearate; ii) dissolving said itraconozole in said molten glyceryl monostearate to form a molten solution of itraconozole in glyceryl monostearate; then iii) adding a stabilizing amount of said hydroxypropylmethylcellulose to said molten solution; and iv) granulating the molten mixture from step (iii) with cooled croscarmellose sodium and optionally a binder to form said granular particle.
CROSS-REFERENCE TO RELATED APPLICATIONS
This is a divisional application of parent application Ser. No. 09/528,624, filed Mar. 20, 2000, in which the benefit of priority of U.S. Provisional Application No. 60/125,914, filed Mar. 24, 1999, and U.S. Provisional Application No. 60/149,680, filed Aug. 19, 1999, is claimed. The disclosures of these applications are herein incorporated by reference.
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