Morphine Formulations
Described is a pellet composition comprising a core element comprising morphine sulfate, a filler and a binder, wherein the morphine sulfate, calculated as the anhydrous form, comprises about 50 wt % to about 85 wt % of the total weight of the core element; and a coating disposed on at least a portion of the core element, the coating comprising an insoluble matrix polymer which is insoluble at pH 1 to 7.5; an enteric polymer which is insoluble at pH 1 to 4 and soluble at pH 6 to 7.5; and an acid soluble polymer which is soluble at a pH of 1 to 4, wherein the ratio of the acid soluble polymer to the enteric polymer is 1.45:1 to 2.5:1 on a weight basis. Also described are dosage forms comprising the disclosed pellets.
1 . A pellet composition comprising:
a core element comprising a morphine sulfate, a filler and a binder, wherein the morphine sulfate, calculated as the anhydrous form, comprises about 50 wt % to about 85 wt % of the total weight of the core element; and
a controlled-release coating disposed on at least a portion of the core element, the coating comprising an insoluble matrix polymer which is insoluble at pH 1 to 7.5; an enteric polymer which is insoluble at pH 1 to 4 and soluble at pH 6 to 7.5; and an acid soluble polymer which is soluble at a pH of 1 to 4, wherein the ratio of the acid soluble polymer to the enteric polymer is 1.45:1 to 2.5:1 on a weight basis.
2 . The composition of claim 1 , wherein the morphine sulfate comprises 60 wt % to about 80 wt % of the core element.
3 . The composition of claim 1 , wherein the ratio of the acid soluble polymer to the enteric polymer is 1.5:1 to 2:1.
4 . The composition of claim 1 , wherein the insoluble matrix polymer comprises about 1 wt % to about 85 wt %, the acid soluble polymer comprises about 25 wt % to about 60 wt % of the coating, and the enteric polymer comprises about 1 wt % to about 24 wt % of the total weight of the coating.
5 . The composition of claim 1 , wherein the controlled-release coating comprises about 8 wt % to about 17 wt % of the total weight of the pellet composition.
6 . The composition of claim 1 , wherein the acid soluble polymer is polyvinyl pyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol having a molecular weight of 1700 to 20,000, polyvinyl alcohol, or a combination comprising one or more of the foregoing polymers.
7 . The composition of claim 6 , wherein the acid soluble polymer comprises polyethylene glycol having a molecular weight of 1700 to 20,000.
8 . The composition of claim 1 , wherein the enteric polymer is cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, a methacrylic acid copolymer, hydroxypropyl methylcellulose acetate succinate, shellac, cellulose acetate trimellitate, or a combination comprising one or more of the foregoing enteric polymers.
9 . The composition of claim 8 , wherein the methacrylic acid copolymer comprises methacrylic acid:acrylic acid ethylester 1:1 copolymer.
10 . The composition of claim 1 , wherein the filler comprises an inert core.
11 . The composition of claim 10 , wherein the inert core comprises a sugar sphere.
12 . The composition of claim 1 , wherein the pellets have a dissolution in 500 mL 0.05 M pH 7.5 phosphate buffer, under the dissolution condition of USP Type I apparatus, 37° C. and 50 rpm of
about 15% to about 25% release at 2 hours,
about 40% to about 60% release at 4 hours, and
about 90% to 100% release at 8 hours
13 . The dosage form of claim 1 , wherein the pellets have a dissolution in 500 mL dissolution media at pH 4.5, under the dissolution condition of USP Type I apparatus, 37° C. and 50 rpm of
about 9% to about 16% release at 4 hours, and
about 18% to about 28% release at 8 hours.
14 . A dosage form comprising a capsule comprising a plurality of pellets, the pellets comprising:
a core element comprising morphine sulfate, a filler and a binder, wherein the morphine sulfate, calculated as the anhydrous form, comprises about 50 wt % to about 85 wt % of the total weight of the core element; and
a coating disposed on at least a portion of the core element, the coating comprising an insoluble matrix polymer which is insoluble at pH 1 to 7.5; an enteric polymer which is insoluble at pH 1 to 4 and soluble at pH 6 to 7.5; and an acid soluble polymer which is soluble at a pH of 1 to 4, wherein the ratio of the acid soluble polymer to the enteric polymer is 1.45:1 to 2.5:1 on a weight basis.
15 . The dosage form of claim 14 , wherein the morphine sulfate comprises 60 wt % to about 80 wt % of the core element.
16 . The dosage form of claim 14 , wherein the ratio of the acid soluble polymer to the enteric polymer is 1.5:1 to 2:1.
17 . The dosage form of claim 14 , wherein the controlled-release coating comprises about 8 wt % to about 17 wt % of the total weight of the pellets.
18 . A pellet composition comprising:
a core element comprising morphine sulfate, a filler and a binder, wherein the morphine sulfate comprises about 50 wt % to about 85 wt % of the total weight of the core element; and wherein the pellets have a dissolution in 500 mL 0.05 M pH 7.5 phosphate buffer, under the dissolution condition of USP Type I apparatus, 37° C. and 50 rpm of
about 15% to about 25% release at 2 hours,
about 40% to about 60% release at 4 hours, and
about 90% to 100% release at 8 hours; and
a dissolution in 500 mL dissolution media at pH 4.5 under the dissolution condition of USP Type I apparatus, 37° C. and 50 rpm of
about 9% to about 16% release at 4 hours, and
about 18% to about 28% release at 8 hours.
19 . The pellet composition of claim 18 , wherein the controlled-release coating comprises an insoluble matrix polymer which is insoluble at pH 1 to 7.5; an enteric polymer which is insoluble at pH 1 to 4 and soluble at pH 6 to 7.5; and an acid soluble polymer which is soluble at a pH of 1 to 4, wherein the ratio of the acid soluble polymer to the enteric polymer is 1.45:1 to 2.5:1 on a weight basis.
20 . The pellet composition of claim 19 , wherein the ratio of the acid soluble polymer to the enteric polymer is 1.5:1 to 2:1.