Sustained release pharmaceutical composition

Claim 2

A sustained release pharmaceutical pellet composition comprising a core element comprising at least one active ingredient of high solubility; and a core coating for the core element which is partially soluble at a highly acidic pH to provide a slow rate of release of active ingredient and wherein the active ingredient is available for absorption at a relatively constant faster rate in the intestine over an extended period of time, such that blood levels of active ingredient are maintained with the therapeutic range over an extended period of time.

Claim 3

A sustained release pharmaceutical pellet composition according to claim 1 wherein the active ingredient of high solubility is selected from antihistamines, antibiotics, antituberculosis agents, colinergic agents, antimuscarinics, sympathomimetics, sympatholytic agents, autonomic drubs, iron preparations, haemostatics, cardiac drugs, antihypertensive agents, vasodilators, non-steroidal antiinflammatory agents, opiate agonists, anticonvulsants, tranquilisers, stimulants, barbiturates, sedatives, expectorants, antiemetics, gastrointestinal drugs, heavy metal antagonists, antithyroid agents, genitourinary smooth muscle relaxants and vitamins.

Claim 4

A sustained release pharmaceutical pellet composition according to claim 2 wherein the active ingredient is an opiate agonist selected from the salts of codeine, dextromoramide, hydrocodone, hydromorphine, pethidine, methadone, morphine and propoxyphene.

Claim 5

A sustained release pharmaceutical pellet composition according to claim 1 wherein the active ingredient is a morphine compound.

Claim 6

A sustained release pharmaceutical pellet composition according to claim 4, wherein the morphine compound is a morphine sulphate compound.

Claim 7

A sustained release pharmaceutical pellet composition according to claim 4, wherein the composition, in use, exhibits less fluctuations in plasma concentrations of the morphine compound at steady state over a 24 hour period, relative to a prior art morphine compound in a sustained release form and/or exhibits less diurnal variation in plasma concentration relative to the prior art morphine compound in a sustained release form.

Claim 8

A sustained release pharmaceutical pellet composition according to claim 6 wherein, in use, the time during the morphine blood levels at steady state are greater than 75% of maximum blood levels (t>0.75Cmax) is approximately 3 hours or greater.

Claim 9

A sustained release pharmaceutical pellet composition according to any one of the preceding claims wherein the core coating, in use, generates a dissolution profile for the sustained release composition, which is equal to or greater than the minimum dissolution profile required to provide substantially bioequivalent bioavailability to a capsule, tablet or liquid containing an equal amount of the at least one active ingredient in an immediate available form.

Claim 10

A sustained release pharmaceutical pellet composition according to claim 8, wherein a first dissolution profile is measured at a pH level approximating that of the stomach and a second dissolution profile is measured at a pH level approximating that of at least one point in the intestine; the first and second dissolution profiles for the sustained release composition each being equal to or greater than the minimum dissolution required to provide substantially equivalent bioavailability to a capsule, tablet or liquid containing an equal amount of the at least one active ingredient in an immediate available form.

Claim 11

A sustained release pharmaceutical pellet composition according to claim 9, wherein the composition, in use, exhibits less fluctuations in plasma concentrations of active ingredient at steady state over a 24 hour period, relative to the active ingredient in an uncoated form and/or exhibits less diurnal variation in plasma concentration of active ingredient relative to prior art capsules or tablets containing the at least one active ingredient in a sustained release form.

Claim 12

A sustained release pharmaceutical pellet composition comprising a core element comprising at least one active ingredient of high solubility; a hybrid core coating, which coating provides a slow rate of release of active ingredient at a highly acidic pH and a relatively constant higher rate of release at a less acid to basic pH over an extended period of time; the hybrid core coating comprising at least one polymer which is substantially insoluble independent of pH; at least one enteric polymer which is substantially insoluble at acidic pH but at least partially soluble at a less acidic to basic pH; and at least one component which is at least partially soluble at acidic pH.

Claim 13

A sustained release pharmaceutical pellet composition comprising a core element comprising at least one active ingredient of high solubility; a hybrid core coating, which coating provides a slow rate of release of active ingredient at a highly acidic pH and a relatively constant higher rate of release at a less acid to basic pH over an extended period of time; the hybrid core coating comprising at least one polymer which is substantially insoluble independent of pH; at least one enteric polymer which is substantially insoluble at acidic pH but at least partially soluble at a less acidic to basic pH; and at least one component which is at least partially soluble at acidic pH.

Claim 14

A sustained release pharmaceutical pellet composition according to claim 11 wherein the hybrid core coating comprises approximately 1 to 85% based on the total weight of the hybrid core coating excluding filler and plasticiser of at least one insoluble matrix polymer selected from ethylcellulose, acrylic ester polymers, methacrylic ester polymers and mixtures thereof; approximately 1 to 60% by weight based on the total weight of the hybrid core coating, excluding filler and plasticiser, of at least one enteric polymer selected from cellulose acetate phthalate, hydroxypropyl methyl-cellulose phthalate (HPMCP), polyvinyl acetate phthalate, methacrylic acid copolymer, hydroxypropyl methylcellulose acetate succinate, shellac, cellulose acetate trimellitate and mixtures thereof; and approximately 1 to 60% by weight based on the total weight of the hybrid core coating, excluding filler and plasticiser, of an at least partially acid soluble component selected from polyvinyl pyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, polyvinyl alcohol and monomers therefor and mixtures thereof.

Claim 15

A sustained release pharmaceutical pellet composition according to claim 12, wherein the hybrid core coating comprises approximately 35 to 75% by weight of the insoluble matrix polymer; approximately 2 to 20% by weight of the enteric polymer; and approximately 15 to 40% by weight of the partially acid-soluble component.

Claim 16

A sustained release pharmaceutical pellet composition according to either of claims 12 and 13 wherein the hybrid core coating further comprises approximately 0 to 50% by weight based on the total weight of the hybrid core coating of at least one plasticiser selected from diethyl phthalate, triethyl citrate, triethyl acetyl citrate, triacetin, tributyl citrate, polyethylene glycol and glycerol and the like; and 0 to approximately 75% by weight based on the total weight of the hybrid core coating of a filler selected from insoluble materials, for example silicon dioxide, talc, alumina, starch, kaolin, polacrilin potassium, powdered cellulose, and microcrystalline cellulose and mixtures thereof.

Claim 17

A sustained release pharmaceutical pellet composition according to claim 13, wherein the hybrid core coating as the formulation Insoluble matrix polymer 45 - 65% ) % excluding solvent Enteric 4 - 15% ) Acid soluble 15 - 35% ) Plasticiser 4 - 30% )

Claim 18

A sustained release pharmaceutical pellet composition according to any one of the preceding claims wherein the core element comprises an effective amount of at least one active ingredient of high solubility; at least one core seed; and at least one binding agent.

Claim 19

A sustained release pharmaceutical pellet composition according to claim 16 wherein the core element comprises approximately 0.1 to 95% based on the total weight of the core element of an active ingredient of high solubility; approximately 5 to 90% by weight based on the total weight of the core element of core seeds; and approximately 0.1 to 45% by weight based on the total weight of the core element of a binding agent selected from polyvinyl pyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose and hydroxyethyl cellulose, sugars and mixtures thereof.

Claim 20

A pharmaceutical sustained release product in a unit dosage form including a plurality of pellets, each pellet having the composition according to any one of the preceding claims.

Claim 21

A sustained release pharmaceutical pellet composition according to claim 16 wherein the core element has a formulation Morphine sulphate 10 to 60% by weight Core seeds 30 to 89.9% by weight Hydroxypropyl methylcellulose 0.1 to 10% by weight

Claim 22

A sustained release pharmaceutical pellet composition according to claim 16 wherein the core element has a formulation Morphine sulphate 10 to 60% by weight Core seeds 30 to 87.5% by weight Povidone 2.5 to 10% by weight

Claim 25

A method according to claim 21, which method further includes the preliminary step of providing at lest one active ingredient of high solubility; at least one binding agent; at least one core seed; and coating the core seeds with the active ingredient and binding agent to form a core element.

Claim 26

A method according to claim 21 which method further includes the preliminary steps of providing at least one active ingredient of high solubility; at least one binding agent; and an effective amount of a solvent, mixing the ingredients; and subjecting the ingredients to an extrusion followed by marumerisation to form a core element.

Claim 28

The use for treating pain-associated conditions in patients requiring such treatment of a sustained release pharmaceutical pellet composition according to any one of the claims 1 to 20.

Claim 29

The use according to claim 25 wherein the pain associated conditions relate to the treatment of acute and chronic pain.

Claim 30

The use according to claim 26 wherein the sustained release pharmaceutical pellet composition is provided in a unit dosage form and administration occurs at intervals of approximately 8 to 24 hours.