Programmable pharmaceutical compositions for chrono drug release

An oral pharmaceutical composition providing a pulsatile release of a first drug and a second drug, the composition comprising:

• a) a multilayer core comprising layers in the following order:
• (i) a first placebo layer comprising at least one polyethylene oxide polymer having an average molecular weight of from about 400,000 Da to about 900,000 Da,
• (ii) a first active layer comprising a first drug, and at least one polyethylene oxide polymer having a molecular weight of less than or equal to 300,000 Da,
• (iii) a second placebo layer comprising at least one polyethylene oxide polymer having an average molecular weight of from about 300,000 Da to about 900,000 Da,
• (iv) a second active layer comprising layer comprising a second drug and at least one polyethylene oxide polymer having a molecular weight of less than or equal to 300,000 Da, and
• (v) a push layer comprising at least one polyethylene oxide polymer having an average molecular weight of greater than or equal to 1000,000 Da, and
• b) a semipermeable membrane surrounding the multilayer core, wherein the semipermeable membrane comprises at least one orifice facing the first placebo layer;
• wherein the layers in the multilayer core are placed in the following order:
• the first placebo layer in fluid communication with the at least one orifice in the semipermeable membrane;
• the first active layer;
• the second placebo layer;
• the second active layer;
• and the push layer facing away from the at least one orifice,
• wherein the first drug and the second drug are selected from the group consisting of amphetamines, methylphenidate, diltiazem, carbamazepine, metoprolol, oxprenolol, nifedipine, albuterol, phenylpropanolamine, pseudoephedrine, chlorpheniramine maleate, prazosin, doxazosin, verapamil, oxybutynin chloride, isradipine, hydromorphone, paliperidone, modafinil, armodafinil, liothyronine, oseltamivir (Tamiflu), rifamycin, and glipizide.

An oral pharmaceutical composition comprising a multilayer core comprising a drug for delayed release;

• a semipermeable membrane containing at least one orifice and surrounding the multilayer core;
• and an immediate release drug layer containing a drug for immediate release and surrounding the semipermeable membrane, wherein the multilayer core comprises a placebo layer, an active layer, and a push layer, wherein:
• (i) the placebo layer comprises at least one polyethylene oxide polymer having an average molecular weight of from about 400,000 Da to about 900,000 Da,
• (ii) the active layer comprises a drug for delayed release, and at least one polyethylene oxide polymer having an average molecular weight of less than or equal to 300,000 Da, and
• (iii) the push layer comprises at least one polyethylene oxide polymer having an average molecular weight of greater than or equal to 1000,000 Da;
• wherein the layers in the multilayer core are placed in the following order:
• the placebo layer in fluid communication with the at least one orifice in the semipermeable membrane;
• the active layer;
• and the push layer facing away from the orifice,
• wherein the drug for delayed release is selected from the group consisting of amphetamines, methylphenidate, diltiazem, carbamazepine, metoprolol, oxprenolol, nifedipine, albuterol, phenylpropanolamine, pseudoephedrine, chlorpheniramine maleate, prazosin, doxazocin, verapamil, oxybutynin chloride, isradipine, hydromorphone, paliperidone, modafinil, armodafinil, liothyronine, oseltamivir (Tamiflu), rifamycin, and glipizide.

A method of treating a condition that requires release of a drug at a rhythm, that matches circadian rhythm of an individual being treated, the method comprising administering to a subject in need thereof, an oral pharmaceutical composition comprising:

• a) a multilayer core comprising a placebo layer, an active layer, and a push layer, wherein:
• (i) the placebo layer comprises at least one polyethylene oxide polymer having an average molecular weight of from about 400K Da to about 900K Da, or intermediate values thereof,
• (ii) the active layer comprises at least one drug, and at least one polyethylene oxide polymer having an average molecular weight of less than or equal to 300K Da,
• (iii) the push layer comprises at least one polyethylene oxide polymer having an average molecular weight of greater than or equal to 1M Da;
• and
• b) a semipermeable membrane, containing at least one orifice and surrounding the core,
• wherein the drug is selected from the group consisting of CNS-acting drugs, cardiovascular drugs, anti-infectives, analgesics, anesthetics, antiarthritics, anticholinergics, anti-asthmatics, antidepressants, antimigraine drugs, armodafinil, modafinil, calcium channel blockers, beta blockers, decongestant, antihypertensives, and ACE inhibitors,
• wherein the layers in the multilayer core are placed in the following order:
• the placebo layer in fluid communication with the at least one orifice in the semipermeable membrane;
• the active layer;
• and the push layer facing away from the at least one orifice,
• wherein the composition is taken at night before going to bed and the drug release is delayed for at least about 4 hours.