Dosage form for time-varying patterns of drug delivery

A dosage form for releasing doses of drug twice a day from a single dosage form, comprising:

• a) a semipermeable membrane that surrounds and forms a compartment, the semipermeable membrane being permeable to the passage of fluid and substantially impermeable to the passage of a drug;
• b) an exterior layer comprising a first drug on the exterior surface of the semipermeable membrane;
• c) a microporous membrane coated on the surface of the exterior layer, the microporous membrane being permeable to the passage of fluid and permeable to the passage of the first drug;
• d) a first composition in the compartment, being drug-free for producing a drug-free interval;
• e) a second composition in the compartment comprising a dose amount of a second drug;
• f) a third composition in the compartment that expands in the presence of fluid that enters the dosage form;
• and
• g) an exit means in the semipermeable membrane, exterior layer, and microporous membrane for connecting the exterior of the dosage form with the compartment.

A method for releasing doses of drug twice a day from a single dosage form to the gastrointestinal tract of a mammal, which method comprises:

• a) admitting the dosage form into the gastrointestinal tract of the mammal, the dosage form comprising:
• i) a compartment;
• ii) a semipermeable membrane that surrounds and forms the compartment, the semipermeable membrane comprising a composition that is permeable to the passage of fluid and is substantially impervious to the passage of a drug;
• iii) an exterior drug layer comprising a dose amount of a first drug on the exterior surface of the semipermeable membrane;
• iv) a microporous membrane coated around the exterior drug layer, the microporous membrane comprising a composition that is permeable to the passage of fluid and permeable to the passage of the first drug;
• v) a first composition in the compartment, the first composition being drug-free for producing a drug-free interval prior to the administration of drug from the compartment;
• vi) a second composition in the compartment comprising a dose amount of a second drug for producing a therapeutic effect;
• vii) a third composition in the compartment that expands in the presence of fluid that enters the device;
• and
• viii) an exit means in the semipermeable wall, external drug layer, and microporous membrane for connecting the exterior of the dosage form with the compartment;
• b) releasing a dose of the first drug from the exterior drug layer by contacting the dosage form with gastrointestinal fluid;
• c) imbibing gastrointestinal fluid into the compartment thereby causing the third composition to expand and push against the second composition;
• and
• d) releasing a dose of the second drug from the second composition after the first composition is released from the compartment.

A method for releasing doses of drug three times a day from a single dosage form to the gastrointestinal tract of a mammal, which method comprises:

• a) admitting the dosage form into the gastrointestinal tract of the mammal, the dosage form comprising:
• i) a compartment;
• ii) a semipermeable membrane that surrounds and forms the compartment, the semipermeable membrane comprising a composition that is permeable to the passage of fluid and is substantially impervious to the passage of a drug;
• iii) an exterior drug layer comprising a dose amount of a first drug on the exterior surface of the semipermeable membrane;
• iv) a microporous membrane coated around the exterior drug layer, the microporous membrane comprising a composition that is permeable to the passage of fluid and is permeable to the passage of the first drug;
• v) an immediate release drug coating at least partially surrounding the exterior of the microporous membrane,
• vi) a first composition in the compartment, the first composition being drug-free for producing a drug-free interval prior to the administration of drug from the compartment;
• vii) a second composition in the compartment comprising a dose amount of a second drug for producing a therapeutic effect;
• viii) a third composition in the compartment that expands in the presence of fluid that enters the device;
• and
• ix) an exit means in the semipermeable membrane, external drug layer, and microporous membrane for connecting the exterior of the dosage form with the compartment;
• b) releasing the immediate release drug coating by contacting the dosage form with the gastrointestinal fluid;
• c) releasing the exterior drug layer after a first delay period from initial contact of the dosage form with gastrointestinal fluid;
• d) imbibing gastrointestinal fluid into the compartment thereby causing the third composition to expand and push against the second composition;
• and
• e) releasing the second drug composition after the first composition is released from the compartment.