Gastroretentive dosage forms for sustained drug delivery
The present disclosure is directed to floating gastroretentive dosage forms with prolonged gastric residence time. The disclosure also provides rapidly expanding sustained release or combined immediate release and sustained release formulations comprising drugs that require targeted release in the proximal gastrointestinal tract for maximum therapeutic benefit. The rapidly expanding floating gastroretentive dosage forms comprise a permeable elastic membrane providing desired characteristics for drug release and mechanical strength to maintain tablet integrity.
1. A floating gastroretentive dosage form comprising:
a) a matrix core that is a sustained release swellable matrix core comprising an active agent, a swellable water-soluble polymer, an acid, and a gas-generating agent; and
b) a water-insoluble permeable elastic membrane containing an orifice and surrounding the matrix core;
wherein the active agent is a highly soluble drug,
wherein the membrane comprises a plasticizer, and a copolymer of ethyl acrylate, methyl methacrylate, and methacrylic acid ester with quaternary ammonium groups,
wherein the plasticizer is present in an amount of about 5% to about 20% w/w of the total plasticizer and copolymer weight, and the copolymer is present in an amount of about 80% to about 95% w/w of the total plasticizer and copolymer weight,
wherein the dosage form provides extended release of the active agent in the patient's stomach for a period of at least 8 hours.
2. The dosage form of claim 1 , wherein the dosage form exhibits at least about 200% volume from its initial volume in gastric fluid within about 30 minutes.
3. The dosage form of claim 1 , wherein the dosage form exhibits at least about 550% volume gain from its initial volume in gastric fluid within about 60 minutes.
4. The dosage form of claim 1 , wherein the dosage form further comprises a superdisintegrant selected from the group consisting of crospovidone; croscarmellose sodium; sodium starch glycolate; low substituted hydroxypropyl cellulose; microcrystalline cellulose; alginic acid; a mixture of mannitol, crospovidone, and polyvinyl acetate; and a mixture of mannitol, starch, crospovidone, croscarmellose sodium, silica, and colloidal silica.
5. The dosage form of claim 4 , wherein the superdisintegrant is crospovidone.
6. The dosage form of claim 1 , wherein the swellable water-soluble polymer in the matrix core is selected from the group consisting of hypromellose, hydroxypropyl cellulose, a polyethylene oxide polymer, a carbomer, and sodium alginate.
7. The dosage form of claim 6 , wherein the swellable water-soluble polymer is hypromellose.
8. The dosage form of claim 1 , wherein the gas generating agent is present in an amount of about 10% to about 18.5% w/w of the matrix core weight.
9. The dosage form of claim 1 , wherein the gas-generating agent comprises a mixture of sodium bicarbonate and calcium carbonate.
10. The dosage form of claim 1 , wherein the plasticizer is selected from the group consisting of triethyl citrate, triacetin, polyethylene glycol, propylene glycol, and dibutyl sebacate.
11. The dosage form of claim 10 , wherein the plasticizer is triethyl citrate.
12. The dosage form of claim 1 , wherein the dosage form exhibits a floating lag time of about 15 minutes or less.
13. A floating gastroretentive dosage form comprising:
a) a matrix core that is an extended release swellable matrix core comprising an active agent, a swellable water-soluble polymer, an acid, and a gas-generating agent; and
b) a water-insoluble permeable elastic membrane containing an orifice and surrounding the matrix core;
wherein the active agent is a highly soluble drug;
wherein the membrane comprises a plasticizer, and a copolymer of ethyl acrylate, methyl methacrylate, and methacrylic acid ester with quaternary ammonium groups,
wherein the plasticizer is present in an amount of about 5% to about 20% w/w of the total plasticizer and copolymer weight, and the copolymer is present in an amount of about 80% to about 95% w/w of the total plasticizer and copolymer weight, and
wherein the dosage form exhibits at least about 200% volume gain from its initial volume in gastric fluid within about 30 minutes.
14. The dosage form of claim 13 , wherein the dosage form further comprises a superdisintegrant selected from the group consisting of crospovidone; croscarmellose sodium; sodium starch glycolate; low substituted hydroxypropyl cellulose; microcrystalline cellulose; alginic acid; a mixture of mannitol, crospovidone, and polyvinyl acetate; and a mixture of mannitol, starch, crospovidone, croscarmellose sodium, silica, and colloidal silica.
15. The dosage form of claim 14 , wherein the superdisintegrant is crospovidone.
16. The dosage form of claim 13 , wherein the swellable water-soluble polymer in the matrix core is selected from the group consisting of hypromellose, hydroxypropyl cellulose, a polyethylene oxide polymer, a carbomer, and sodium alginate.
17. The dosage form of claim 16 , wherein the swellable water-soluble polymer is hypromellose.
18. The dosage form of claim 13 , wherein the dosage form provides extended release of the active agent in a patient's stomach for a period of at least 8 hours.
19. The dosage form of claim 13 , wherein the dosage form exhibits at least about 550% volume gain from its initial volume in gastric fluid within about 60 minutes.
20. The dosage form of claim 13 , wherein the gas-generating agent comprises a mixture of sodium bicarbonate and calcium carbonate.
21. The dosage form of claim 13 , wherein the plasticizer is selected from the group consisting of triethyl citrate, triacetin, polyethylene glycol, propylene glycol, and dibutyl sebacate.
22. The dosage form of claim 21 , wherein the plasticizer is triethyl citrate.
23. The dosage form of claim 13 , wherein the dosage form exhibits a floating lag time of about 15 minutes or less.
24. A floating gastroretentive dosage form comprising:
a) a matrix core that is an extended release swellable matrix core comprising an active agent, a swellable water-soluble polymer, an acid, and a gas-generating agent; and
b) a water-insoluble permeable elastic membrane containing an orifice and surrounding the matrix core;
wherein the active agent is a highly soluble drug,
wherein the membrane comprises a plasticizer, and a copolymer of ethyl acrylate, methyl methacrylate, and trimethyl aminoethyl methacrylate chloride,
wherein the plasticizer is present in an amount of about 5% to about 20% w/w of the total plasticizer and copolymer weight, and the copolymer is present in an amount of about 80% to about 95% w/w of the total plasticizer and copolymer weight, and
wherein the dosage form exhibits a floating lag time of 20 minutes or less.
25. A floating gastroretentive dosage form comprising:
a) a matrix core that is an extended release swellable matrix core comprising a highly soluble drug, a swellable water-soluble polymer, an acid, and a gas-generating agent;
b) a water-insoluble permeable elastic membrane containing an orifice and surrounding the matrix core; and
c) an immediate release layer over the water-insoluble permeable elastic membrane, wherein the membrane comprises a plasticizer, and a copolymer of ethyl acrylate, methyl methacrylate, and trimethyl aminoethyl methacrylate chloride,
wherein the plasticizer is present in an amount of about 5% to about 20% w/w of the total plasticizer and copolymer weight, and the copolymer is present in an amount of about 80% to about 95% w/w of the total plasticizer and copolymer weight,
wherein the immediate release layer contains a drug for immediate release,
and wherein the dosage form provides immediate release of the drug for immediate release, and extended release of the highly soluble drug for a period of at least 8 hours.
26. A floating gastroretentive dosage form comprising:
a) a matrix core that is an extended release swellable matrix core comprising a highly soluble drug, a swellable water-soluble polymer, an acid, and a gas-generating agent; and
b) a water-insoluble permeable elastic membrane containing an orifice and surrounding the matrix core;
wherein the membrane comprises a plasticizer, and a copolymer of ethyl acrylate, methyl methacrylate, and trimethyl aminoethyl methacrylate chloride,
wherein the highly soluble drug exhibits site-specific absorption in the upper GI tract,
wherein the plasticizer is present in an amount of about 5% to about 20% w/w of the total plasticizer and copolymer weight, and the copolymer is present in an amount of about 80% to about 95% w/w of the total plasticizer and copolymer weight, and
wherein the dosage form improves bioavailability of the highly soluble drug by extending the release of the drug in the vicinity of its absorption site(s) and without premature transit into nonabsorbing regions of the GI tract.
27. A floating gastroretentive dosage form comprising:
a) a matrix core that is a sustained release swellable matrix core comprising an active agent, a swellable water-soluble polymer, an acid, and a gas-generating agent; and
b) a water-insoluble permeable elastic membrane containing an orifice and surrounding the matrix core;
wherein the active agent is a highly soluble drug,
wherein the membrane comprises a plasticizer, and a copolymer selected from the group consisting of a copolymer of ethyl acrylate, methyl methacrylate, and methacrylic acid ester with quaternary ammonium groups,
wherein the plasticizer is present in an amount of about 5% to about 20% w/w of the total plasticizer and copolymer weight, and the copolymer is present in an amount of about 80% to about 95% w/w of the total plasticizer and copolymer weight,
wherein the dosage form provides extended release of the active agent in a patient's stomach for a period of at least 12 hours, and
wherein the dosage form reduces side effects and improves patient compliance by extending the release of the active agent in the stomach.