Chronotherapeutic dosage forms containing glucocorticosteroid and methods of treatment

A delayed release oral solid dosage form comprising:

• a core comprising a therapeutically effective amount of a glucocorticosteroid drug, and an agglomerated delayed release material compression coated onto said core, said agglomerated delayed release material comprising a gum selected from the group consisting of a homopolysaccharide, a heteropolysaccharide, and a mixture of a homopolysaccharide and a heteropolysaccharide, together with a pharmaceutically acceptable excipient, said compression coating delaying the release of said drug from said dosage form for a predetermined period of time after exposure of the dosage form to an aqueous solution.

A delayed release oral solid dosage form comprising:

• a core comprising a therapeutically effective amount of a glucocorticosteroid drug and an effective amount of a disintegrant, and an agglomerated delayed release material compression coated onto said core, said agglomerated delayed release material consisting essentially of one or more natural or synthetic pharmaceutically acceptable gums and one or more optional pharmaceutically acceptable excipients, said compression coating delaying the release of said drug from said dosage form for a predetermined period of time after exposure of the dosage form to an aqueous solution.

The delayed release oral solid dosage form of claim 26, wherein said core further comprises from about 5 to about 20 percent disintegrant, by weight.

The delayed release oral solid dosage form of claim 27, wherein said disintegrant is selected from the group consisting of starch, veegum, crospovidone, cellulose, kaolin, microcrystalline cellulose, crosslinked polyvinyl pyrrolidone, and mixtures thereof.

A delayed release oral solid dosage form comprising:

• a core comprising a therapeutically effective amount of a glucocorticosteroid drug and a disintegrant, and a delayed release material compression coated onto said core, said delayed release material comprising one or more natural or synthetic gums, said compression coating delaying the release of said drug from said dosage form for a predetermined period of time after exposure of the dosage form to an aqueous solution, said disintegrant being included in said core in an amount effective to cause the release of at least about 50 percent of said drug into said aqueous solution within one hour after said predetermined period of time.

A delayed release oral solid tablet, comprising:

• a tablet core comprising a therapeutically effective amount of a glucocorticosteroid drug, and a delayed release material compression coated onto said core, said delayed release material comprising one or more natural or synthetic gums, said gums comprising from about 6.5 percent to about 83 percent of the tablet by weight, said compression coating delaying the release of said drug from said dosage form for a period of time from about 2 to about 18 hours after exposure of the dosage form to an aqueous solution.

A chronotherapeutic, delayed release oral solid dosage form comprising a core comprising from about 0.01 mg to about 40 mg glucocorticosteroid, and a delayed release material compression coated onto said core, said delayed release material comprising one or more natural or synthetic gums, said compression coating comprising from about 75 to about 94 percent by weight of the oral solid dosage form, and the ratio of the core to gum in said compression coating being from about 1:0.37 to about 1:5, by weight, said compression coating delaying the release of said glucocorticosteroid from said dosage form for a period of time from about 2 to about 18 hours after exposure of the dosage form to an aqueous solution.

A method of preparing a chronotherapeutic oral solid dosage form of a glueocorticosteroid, comprising:

• preparing a core comprising a therapeutically effective amount of a glucocorticosteroid and from about 5 to about 20% disintegrant, by weight of the core,
• preparing a granulate of a delayed release material comprising one or more natural or synthetic gums,
• compression coating said granulate onto said core, said compression coating delaying the release of said glucocorticosteroid from said dosage form until after a period of time from about 2 to about 18 hours after exposure of the dosage form to an aqueous solution.

A method of treating early morning inflammation or arthritis comprising:

• orally administering to a human at bedtime an oral solid dosage comprising a core comprising a therapeutically effective amount of a glucocorticosteroid;
• and a delayed release compression coating on said core comprising one or more natural or synthetic pharmaceutically acceptable gums;
• said compression coating delaying the release of said glucocortosteroid from said dosage form for a time period until at least about 4 hours after oral administration.

The method of claim 46, wherein after oral administration of the dosage form, the glucocorticosteroid is not released from the dosage form for about 4 to about 12 hours.