Delivery system comprising means for controlling internal pressure

Claim 2

An improved delivery system for administering a beneficial agent to an environment of use, the delivery system comprising: i) a wall that surrounds a lumen, the wall comprising in at least a part a semipermeable composition, ii) a thermo-responsive composition in the lumen that forms a dispensable formulation at the temperature of the environment of use, iii) a beneficial agent mixed with the thermo-responsive composition, iv) push means in the lumen for displacing the thermo-responsive composition from the delivery system, and v) an exit opening in the wall that communicates with the lumen; wherein, the improvement comprises: a) a viscosity-inducing amount of an inert viscosity-inducing agent in the thermo-responsive composition for increasing the viscosity of the thermo-responsive composition, and b) a pressure-inducing exit member in the exit opening in the wall for increasing the pressure inside the lumen, the exit member having from 1 to 50 exit ports or passageways; wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit member is greater than 4 psi.

Claim 3

An improved delivery system according to claim 1 wherein the viscosity-inducing agent is silicon dioxide.

Claim 4

An improved delivery system according to claim 1 wherein the viscosity-inducing agent is selected from the group consisting of silica, sand, precipitated silica, amorphous silica, colloidal silicon dioxide, fused silica, quartz, silica gel, and a siliceous composition.

Claim 5

An improved delivery system according to claim 1 wherein the process comprises positioning a releasable pressure-inducing exit member in the exit opening in the wall.

Claim 6

An improved delivery system according to claim 1 wherein the exit member is an insert for placement in the exit opening in the wall of the dispenser.

Claim 7

An improved delivery system according to claim 1 wherein the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.

Claim 8

An improved delivery system according to claim 5 wherein the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.

Claim 9

An improved delivery system according to claim 1 wherein the beneficial agent is avermectin or ivermectin.

Claim 10

An improved delivery system according to claim 1 wherein the push means comprises an osmagent, an osmopolymer or an osmagent together with an osmopolymer.

Claim 11

An improved delivery system according to claim 1 wherein the dispenser further comprises an inert partition in the lumen between the thermo-responsive composition and the push means.

Claim 12

An improved delivery system according to claim 1 wherein the delivery system further comprises a density member in the lumen for maintaining the delivery system in the environment of use over time, the density member having a density greater than the density of the environment of use.

Claim 13

An improved delivery system according to claim 11 wherein the density member comprises a weight with a bore in the weight, and the exit member is in contact with the bore.

Claim 14

An improved delivery system according to claim 11 wherein the environment of use is an animal.

Claim 15

An improved delivery system according to claim 11 wherein the environment of use is a ruminant animal.

Claim 16

An improved controlled release bolus for administering ivermectin to a ruminant animal, the bolus comprising: i) a wall that surrounds a lumen, the wall comprising in at least a part a semipermeable composition, ii) a thermo-responsive composition in the lumen that forms a dispensable formulation in the ruminant animal, iii) a therapeutically effective amount of ivermectin mixed with the thermo-responsive composition, iv) a density member in the lumen for maintaining the bolus in the rumen over time, v) push means in the lumen for displacing the thermo-responsive composition from the bolus, the push means comprising a composition selected from an osmagent, an osmopolymer or an osmagent together with an osmopolymer, vi) an inert partition in the lumen between the thermo-responsive composition and the push means, and vi) an exit opening in the wall that communicates with the lumen; wherein, the improvement comprises: a) a viscosity-increasing amount of an inert viscosity-inducing agent in the thermo-responsive composition for increasing the viscosity of the thermo-responsive composition, and b) a pressure-inducing exit member in the exit opening in the wall for increasing the pressure inside the lumen, the exit member having from 1 to 50 exit ports or passageways; wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit member is greater than 4 psi.

Claim 17

An improved controlled release bolus for administering ivermectin to a ruminant animal, the bolus comprising: i) a wall that surrounds a lumen, the wall comprising in at least a part a semipermeable composition, ii) a thermo-responsive composition in the lumen that forms a dispensable formulation in the ruminant animal, iii) a therapeutically effective amount of ivermectin mixed with the thermo-responsive composition, iv) a density member in the lumen for maintaining the bolus in the rumen over time, v) push means in the lumen for displacing the thermo-responsive composition from the bolus, the push means comprising a composition selected from an osmagent, an osmopolymer or an osmagent together with an osmopolymer, vi) an inert partition in the lumen between the thermo-responsive composition and the push means, and vi) an exit opening in the wall that communicates with the lumen; wherein, the improvement comprises: a) a viscosity-increasing amount of an inert viscosity-inducing agent in the thermo-responsive composition for increasing the viscosity of the thermo-responsive composition, and b) a pressure-inducing exit member in the exit opening in the wall for increasing the pressure inside the lumen, the exit member having from 1 to 50 exit ports or passageways; wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit member is greater than 4 psi.

Claim 18

An improved controlled release bolus according to claim 15 wherein the viscosity-inducing agent is silicon dioxide.

Claim 19

An improved controlled release bolus according to claim 15 wherein the density member comprises a weight with a bore in the weight, and the exit member is in contact with the bore.

Claim 20

An improved controlled release bolus according to claim 15 wherein the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.

Claim 21

An improved controlled release bolus according to claim 17 wherein the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.

Claim 22

An improved controlled release bolus according to claim 15 wherein ivermectin is released substantially immediately to the ruminant animal by means of prehydrating the bolus with a pharmaceutically acceptable fluid prior to administering the bolus to the animal.

Claim 23

An improved delivery system for administering a beneficial agent to an environment of use, the delivery system comprising: i) a wall that surrounds a lumen, ii) a thermo-responsive composition in the lumen, iii) a beneficial agent mixed with the thermo-responsive composition, iv) optionally, a density member in the lumen for increasing the weight of the dispenser, v) push means in the lumen for displacing the thermo-responsive composition from the dispenser, and vi) an exit opening in the wall that communicates with the lumen; wherein, the improvement comprises: a) a viscosity-inducing amount of an inert viscosity-inducing agent mixed into the thermo-responsive composition for increasing the viscosity of the thermo-responsive composition to increase the internal pressure of the dispenser; wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit opening is greater than 4 psi.

Claim 24

An improved delivery system for administering a beneficial agent to an environment of use, the delivery system comprising: i) a wall that surrounds a lumen, ii) a thermo-responsive composition in the lumen, iii) a beneficial agent mixed with the thermo-responsive composition, iv) optionally, a density member in the lumen for increasing the weight of the dispenser, v) push means in the lumen for displacing the thermo-responsive composition from the dispenser, and vi) an exit opening in the wall that communicates with the lumen; wherein, the improvement comprises: a) a viscosity-inducing amount of an inert viscosity-inducing agent mixed into the thermo-responsive composition for increasing the viscosity of the thermo-responsive composition to increase the internal pressure of the dispenser; wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit opening is greater than 4 psi.

Claim 25

An improved delivery system according to claim 21 wherein the viscosity-inducing agent is silicon dioxide.

Claim 26

An improved delivery system according to claim 21 wherein the viscosity-inducing agent is selected from the group consisting of silica, sand, precipitated silica, amorphous silica, colloidal silicon dioxide, fused silica, quartz, silica gel, and a siliceous composition.

Claim 27

An improved delivery system according to claim 21 wherein the viscosity-inducing agent increases the stress to flow of the thermo-responsive composition.

Claim 28

An improved delivery system for administering a beneficial agent to an environment of use, the delivery system comprising: i) a wall that surrounds a lumen, ii) a thermo-responsive composition in the lumen, iii) a beneficial agent mixed with the thermo-responsive composition, iv) optionally, a density member in the lumen for increasing the weight of the dispenser, v) push means in the lumen for displacing the thermo-responsive composition from the dispenser, and vi) an exit opening in the wall that communicates with the lumen; wherein, the improvement comprises: a) a pressure-inducing exit member in the exit opening in the wall for increasing the pressure inside the lumen, the exit member having from 1 to 50 exit ports or passageways; wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit member is greater than 4 psi.

Claim 29

An improved delivery system for administering a beneficial agent to an environment of use, the delivery system comprising: i) a wall that surrounds a lumen, ii) a thermo-responsive composition in the lumen, iii) a beneficial agent mixed with the thermo-responsive composition, iv) optionally, a density member in the lumen for increasing the weight of the dispenser, v) push means in the lumen for displacing the thermo-responsive composition from the dispenser, and vi) an exit opening in the wall that communicates with the lumen; wherein, the improvement comprises: a) a pressure-inducing exit member in the exit opening in the wall for increasing the pressure inside the lumen, the exit member having from 1 to 50 exit ports or passageways; wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit member is greater than 4 psi.

Claim 30

An improved delivery system according to claim 25 wherein the exit member is a releasable pressure-inducing exit member.

Claim 31

An improved delivery system according to claim 25 wherein the exit member is an insert for placement in the exit opening in the wall of the delivery system.

Claim 32

An improved delivery system according to claim 25 wherein the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.

Claim 33

An improved delivery system according to claim 28 wherein the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.