Osmotic dispenser with gas generating means

• US 4,036,228 A
• Filed: 09/11/1975
• Issued: 07/19/1977
• Est. Priority Date: 09/11/1975
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Theeuwes, Felix
• Primary Examiner(s): Charles, Lawrence
• Application Number:
  US05/612,465
• Time in Patent Office: 677 Days
• Field of Search: 128/260, 128/225, 128/261, 128/270, 128/213
• US Class Current: 424/473
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence

Abstract

An osmotic device for delivering an active agent is disclosed. The device is comprised of a wall surrounding a compartment and has a passageway through the wall for dispensing the agent. The wall is formed of a material permeable to an external fluid and substantially impermeable to agent and a gas generating means. The compartment is comprised of an active agent and a gas generating means that either exhibits an osmotic pressure gradient against the external fluid, or the means is mixed with an osmotically effective compound that exhibits an osmotic pressure gradient against the fluid. Agent is released by fluid being imbibed through the wall into the compartment at a rate controlled by the permeability of the wall and the osmotic pressure gradient across the wall, which fluid wets the means causing it to react and produce an effervescent solution containing agent that is dispensed under pressure through the passageway to the exterior of the device.

Claims

1. An osmotic device for the continuous dispensing of an active agent to an environment of use, said device comprising:

a. a shaped wall formed of a semipermeable material that maintains its integrity during the dispensing period and which wall is characterized as permeable to the passage of an external fluid in the environment of use and substantially impermeable to the passage of agent;

b. the wall surrounding and forming a compartment containing an active agent and an effervescent couple which couple is soluble in the external fluid and which couple exhibits an osmotic pressure gradient across the wall against the external fluid;

c. a passageway in the wall communicating with the compartment and the exterior of the device for dispensing agent from the device; and

d. wherein in operation with the device in the environment of use, external fluid is continuously imbibed through the wall into the compartment in a tendency towards osmotic equilibrium at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall, thereby wetting the couple which reactively produces an effervescent solution which dispenses agent through the passageway from the device at a controlled rate over a prolonged period of time.

2. An osmotic device according to claim 1 wherein the effervescent couple comprises an acidic component and a basic component which when brought into fluid reactive contact effervesces.

3. An osmotic device according to claim 1 wherein the active agent contains potassium for use in potassium replacement therapy.

4. An osmotic device according to claim 1 wherein the effervescent couple contains a member selected from the group of pharmaceutically acceptable acids consisting of malic, fumaric, tartaric, itaconic, maleic, citric, adipic, succinic, mesaconic, glycine and mixtures thereof.

5. An osmotic device according to claim 1 wherein the effervescent couple contains a member selected from the group consisting of sodium carbonate, potassium carbonate, calcium carbonate, magnesium carbonate, sodium bicarbonate, potassium bicarbonate, magnesium bicarbonate, calcium bicarbonate, and mixtures thereof.

6. An osmotic device according to claim 1 wherein the agent is acetylasalicylic acid and the couple consists of sodium bicarbonate and citric acid.

7. An osmotic device according to claim 1 wherein the compartment contains sodium bicarbonate, potassium bicarbonate and citric acid.

8. An osmotic device according to claim 1 wherein the compartment contains a composition comprising potassium bicarbonate, potassium chloride, citric acid and a carbohydrate.

9. An osmotic device according to claim 1 wherein the compartment contains citric acid, sodium bicarbonate and a ferrous compound.

10. An osmotic device according to claim 1, wherein the active agent is a member selected from the group consisting of acetazolamide, dichlorophenamide quinidine, norethindrone, norethynordrel, diazepam, norethynodrel with ethynylestradiol 3-methyl ether, metazolamide, pentaerythritol tetranitrate, salicylamide, ascorbic acid, calcium lactate, salicyclic acid, sodium salicylate, choline salicylate, acetaminophen and phenacetin.

11. An osmotic device for the continuous dispensing of an active agent to an environment of use, said device comprising:

a. a shaped wall formed of a semipermeable material that maintains its integrity during the dispensing period and is characterized as permeable to the passage of an external fluid in the envornment of use and substantially impermeable to the passage of agent;

b. the wall surrounding and forming a compartment containing an active agent characterized by having limited solubility in the external fluid and exhibiting a limited osmotic pressure gradient across the wall against the fluid;

c. an effervescent couple that is soluble in the fluid and which couple exhibits an osmotic pressure gradient across the wall against the fluid present in the compartment;

d. a passageway in the wall for dispensing agent from the device, said passageway structured and adapted for dispensing an effervescent solution from the device, and;

e. wherein in operation with the device in the envornment of use, external fluid is imbibed through the wall into the compartment in a tendency towards osmotic equilibrium at a rate controlled by the permeability of the wall and the osmotic gradient across the wall, thereby continuously dissolving the couple which reactively effervesces and forms a solution-containing suspended agent that is dispensed through the passageway from the device at a controlled rate for a prolonged period of time.

12. An osmotic device for continuous dispensing of an agent according to claim 11 wherein the compartment additionally contains a surface-active agent.

13. An osmotic device for dispensing an active agent according to claim 11 wherein the compartment contains acetylsalicylic acid, citric acid, sodium bicarbonate and monocalcium phosphate dibasic.

14. An osmotic device for continuously dispensing an active agent to an environment of use, said device comprising:

a. a shaped wall formed of a semipermeable material that maintains its integrity during the dispensing period, is permeable to the passage of an external fluid in the environment of use and substantially impermeable to the passage of agent;

b. the wall surrounding and forming a compartment containing an active agent having limited solubility in the external fluid, and a foam-forming agent;

c. an effervescent couple present in the compartment, which couple is soluble in the fluid, exhibits an osmotic pressure gradient across the wall against the fluid and is capable of evolving gaseous carbon dioxide;

d. a passageway in the wall structured and adapted for dispensing foam from the device; and

,

e. wherein in operation with the device in the environment of use, external fluid is imbibed through the wall into the compartment causing the couple to evolve carbon dioxide which in the presence of fluid and the foam-forming agent produces foam that dispenses active agent through the passageway from the osmotic device at a controlled rate over a prolonged period of time.

15. An osmotic device according to claim 14, wherein the couple is comprised of a member selected from the group consisting of an inorganic and organic acid, and a compound capable of evolving carbon dioxide in the presence of fluid and the acid and which compound is selected from the group consisting of pharmaceutically acceptable alkali metal carbonates, alkali metal bicarbonates, alkaline earth carbonates, alkaline earth bicarbonates and mixtures thereof.

16. An osmotic device according to claim 15 wherein the active agents are mixed with a surfactant.

20. An oral osmotic device according to claim 16 wherein the device contains an an orally administrable pharmaceutically acceptable analgesic selected from the group consisting of acetylsalicylic acid, salicylic acid, sodium salicylate, choline salicylate, acetaminophen and phenacetin and mixtures thereof.

17. An oral osmotic device for dispensing an active agent, said device comprising:

a. a wall formed of a semipermeable material that maintains its integrity during the dispensing period, is permeable to the passage of external fluid present in the gastrointestinal tract and is substantially impermeable to the passage of agent, the wall surrounding;

b. a compartment containing the agent comprised of at least one member selected from the group consisting of 100 to 1500 mg of potassium bicarbonate, 100 to 1500 mg of sodium bicarbonate, 10 to 750 mg of calcium carbonate and 50 to 100 mg of magnesium carbonate and mixtures thereof, blended with at least one member selected from the group consisting of 50 to 1500 mg of citric acid and 500 to 1500 mg of glycine and mixtures thereof,

c. a passageway in the wall adapted and sized for dispensing the agent from the device; and

d. wherein in operation with the device in the environment of use, external fluid is imbibed through the wall into the compartment at a controlled rate causing the agent to effervesce and be dispensed through the passageway from the device.

18. An oral osmotic device according to claim 17 wherein the agent is also blended with at least one member selected from the group consisting of 25 to 175 mg of magnesium oxide, 50 to 750 mg of magnesium trisilicate and 50 to 750 mg of dihydroxyaluminum aminoacetate and mixtures thereof.

19. An oral osmotic device according to claim 17 wherein the device is used for neutralizing excessive acidity in the gastrointestinal tract.

21. An osmotic device for continuously dispensing an active agent to an environment of use, said device comprising:

a. a shaped wall formed of a semipermeable material that maintains its integrity during the dispensing period, is permeable to the passage of an external fluid in the environment of use and is substantially impermeable to the passage of agent, the wall surrounding and defining;

b. a compartment containing (1) an active agent, (2) an effervescent composition which composition reactively effervesces in the presence of fluid in the compartment, and (3) an osmotically-effective compound which compound is soluble in the external fluid and also exhibits an osmotic pressure gradient across the wall against the fluid;

c. a passageway in the wall structured and adapted for dispensing an agent from the device; and

,

d. wherein in operation with the device in the environment of use, external fluid from the environment is imbibed through the wall into the compartment in a tendency towards osmotic equilibrium at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall thereby causing the composition to effervesce and dispense the active agent through the passageway at a controlled rate from the device.

22. An osmotic device according to claim 21 wherein the compartment contains a foam-forming agent.

23. An osmotic device according to claim 21 wherein the compartment contains a surfactant.

24. A method for continuously administering an active agent having limited solubility in gastrointestinal fluid to the gastrointestinal tract of a warm blooded animal comprising:

a. admitting into the gastrointestinal tract an osmotic device comprising;

1. a shaped wall formed of a semipermeable material that is permeable to the passage of gastrointestinal fluid and is substantially impermeable to active agent;

2. the wall surrounding and forming a compartment containing the active agent, a foam-forming agent, and an effervescent couple which couple is soluble in fluid that enters the compartment and which couple exhibits an osmotic pressure gradient across the wall against the fluid;

3. a passageway in the wall for administering agent from the device;

b. dissolving said couple in the compartment in the gastrointestinal fluid being imbibed through the wall into the compartment at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall to continuously dissolve the couple and produce an effervescent solution which reacts with the foam-forming agent to produce foam that mixes with the active agent; and

,

c. administering the active agent from the device at a controlled and continuous rate by foam-transporting the agent through the passageway to the gastrointestinal tract over a prolonged period of time.