Gastroretentive Solid Oral Dosage Forms with Swellable Hydrophilic Polymer
The disclosure provides multiparticulate systems that give release of active agents with a narrow window of absorption such that there is bioavailability to a patient. The disclosure provides a composition comprising microparticulates comprising a swellable hydrophilic polymer and an active agent, wherein the swellable hydrophilic polymer is substantially non-crosslinked intramolecularly, and the size of the microparticulates is about 500 μm or less.
1 . A composition comprising microparticulates comprising a swellable hydrophilic polymer and an active agent, wherein
the swellable hydrophilic polymer is substantially non-crosslinked intramolecularly; and
the size of the microparticulates is about 500 μm or less.
2 . The composition of claim 1 , wherein the swellable hydrophilic polymer is selected from cellulose polymers and their derivatives, polysaccharides and their derivatives, polyalkylene oxides, polyethylene glycols, chitosan, poly(vinyl alcohol), xanthan gum, maleic anhydride copolymers, poly(vinyl pyrrolidone), starch and starch-based polymers, poly(2-ethyl-2-oxazoline), poly(ethyleneimine), polyurethane hydrogels, and combinations comprising one or more of the foregoing polymers.
3 . The composition of claim 1 , wherein the swellable hydrophilic polymer is selected from cellulose and derivatives thereof.
4 . The composition of claim 1 , wherein the swellable hydrophilic polymer is selected from cellulose (such as microcrystalline cellulose), hydroxymethylcellulose, hydroxyethylcellulose (HEC), hydroxypropylmethylcellulose (HPMC), hydroxypropycellulose (HPC), methylcellulose (MC or METHOCEL), ethylcellulose (EC), hydroxyethylmethylcellulose (HEMC), ethylhydroxy-ethylcellulose (EHEC), and carboxymethylcellulose.
5 . The composition of claim 1 , wherein the swellable hydrophilic polymer is hydroxypropylmethylcellulose (HPMC).
6 . The composition of claim 1 , wherein the swellable hydrophilic polymer is microcrystalline cellulose or ethylcellulose (EC).
7 . The composition of claim 1 , wherein the size of the microparticulates is about 300 μm or less.
8 . The composition of claim 1 , wherein the size of the microparticulates is about 250 μm or less.
9 . The composition of claim 1 , wherein the size of the microparticulates is about 200 μm or less.
10 . The composition of claim 1 , wherein the active agent is a Class II, or Class III or Class IV compound, according to the biopharmaceutical classification of drugs in terms of their solubility and intestinal permeability by the FDA.
11 . The composition of claim 1 , wherein the active agent is baclofen.
12 . The composition of claim 1 , wherein the active agent is levodopa.
13 . The composition of claim 1 , further comprising a controlled release coating.
14 . The composition of claim 13 , the controlled release coating is EUDRAGIT® polymer.
15 . A composition comprising microparticulates comprising a swellable hydrophilic polymer and an active agent, wherein
the swellable hydrophilic polymer is substantially non-crosslinked HPMC intramolecularly; and
the size of the microparticulates is about 500 μm or less.
16 . A method of preparing a composition comprising microparticulates comprising a swellable hydrophilic polymer and an active agent, wherein the swellable hydrophilic polymer is substantially non-crosslinked intramolecularly; and the size of the microparticulates is about 500 μm or less, the method comprising:
mixing solid swellable hydrophilic polymer and solid active agent.
17 . The method of claim 16 , further comprising micronizing the solid active agent.
18 . A composition produced by the method of any one of claims 16 and 17 .
19 . A method of preparing a composition comprising microparticulates comprising a swellable hydrophilic polymer and an active agent, wherein the swellable hydrophilic polymer is substantially non-crosslinked intramolecularly; and the size of the microparticulates is about 500 μm or less, the method comprising:
dissolving an active agent in a solution or suspension;
coating a nonpareil seed with the solution or suspension comprising the active agent; and
mixing a solid swellable hydrophilic polymer with the nonpareil seeds coated with active agent.
20 . A composition produced by the method of claim 19 .
21 . A method of preparing a composition comprising microparticulates comprising a swellable hydrophilic polymer and an active agent, wherein the swellable hydrophilic polymer is substantially non-crosslinked intramolecularly; and the size of the microparticulates is about 500 μm or less, the method comprising:
mixing an active agent with a swellable hydrophilic polymer;
wet granulating the mixture of active agent and swellable hydrophilic polymer;
extruding the mixture of active agent and swellable hydrophilic polymer; and
subjecting the mixture of active agent and swellable hydrophilic polymer to spheronization to obtain microparticles.
22 . A composition produced by the method of claim 21 .
23 . A method of preparing a composition comprising microparticulates comprising a swellable hydrophilic polymer and an active agent, wherein the swellable hydrophilic polymer is substantially non-crosslinked intramolecularly; and the size of the microparticulates is about 500 μm or less, the method comprising:
mixing an active agent with an inert polymer;
wet granulating the mixture of active agent and inert polymer;
extruding the mixture of active agent and inert polymer;
subjecting the mixture of active agent and inert polymer to spheronization to obtain microparticles; and
mixing the microparticles with a swellable hydrophilic polymer.
24 . A composition produced by the method of claim 22 .