Therapeutic device for osmotically dosing at controlled rate

• US 4,160,020 A
• Filed: 12/27/1977
• Issued: 07/03/1979
• Est. Priority Date: 11/24/1975
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Ayer, Atul D., Theeuwes, Felix
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US05/864,954
• Time in Patent Office: 553 Days
• Field of Search: 424/15, 424/19, 424/21, 424/35, 128/260
• US Class Current: 424/436
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms

Abstract

An osmotic device is disclosed for delivering an active agent. The device comprises a wall surrounding a compartment with a passageway through the wall for releasing the agent. The wall comprises a material permeable to an external fluid and substantially impermeable to agent and at least one additional material independently selected from materials that impart stability to the wall, enhance the permeability of the wall to fluids, or aid in forming the wall. The compartment contains an agent that exhibits an osmotic pressure gradient across the wall against an external fluid, or the agent is mixed with an osmotically effective compound that exhibits an osmotic pressure gradient against the fluid. Agent is released from the device by fluid being imbided through the wall into the compartment at a rate controlled by the permeability of the wall and the osmotic pressure gradient across the wall, thereby producing a solution containing agent that is released through the passageway at a controlled rate over time.

Claims

1. An osmotic device for dispensing a drug to an animal comprising:

(a) a shaped wall that is substantially inert and maintains its physical and chemical integrity during the controlled dispensing of the drug, said wall a composition comprising (1) a polymer that is permeable to the passage of an external fluid and substantially impermeable to the passage of drug, said polymer having the following formula;

##STR3## wherein R₁, R₂ and R₃ are a member selected from the group consisting of hydrogen;

alkyl;

alkenyl;

amino;

alkanoyl;

alkanoyl substituted with a member selected from the group consisting of alkoxy, halogen, hydroxyl, alkanoyl, carboalkyl, carboalkoxy and cyanoalkoxy;

aroyl;

aroyl substituted with a member selected from the group consisting of hydroxyl, carboxyl, carboalkyl and cyano;

benzyl;

carboalkyl;

carboxyalkyl;

dialkoxyalkyl;

dithiocarbonyl;

hydroxyalkyl;

cyanoalkyl;

nitro;

phenyl;

sulfoalkyl;

the alkali metal salts thereof; and

wherein said polymer exhibits a degree of substitution at R₁, R₂ and R₃ of greater than 0 up to 3, and n is greater than 5, and (2) a wall forming polymer that is a different polymer than (1) which polymer (2) has the following formula;

##STR4## wherein R₅, R₆ and R₇ are a member selected from the group consisting of hydroxyl, nitrate;

hydroxyalkyl;

alkoxy;

aryloxy;

hydroxyalkoxy;

hydroxyalkalkoxy;

trityloxy;

with at least one of R₅, R₆ and R₇ a member selected from the group consisting of aryloxy;

alkanoyloxy;

carboxyalkoxy;

carbamoyloxyalkoxy;

carboxyalkoxyacyloxy;

carboxy;

carboxybenzoyl;

carboxybenzoyloxy;

carboxybenzoyloxyalkoxy; and

dialkylaminohydroxyalkoxy;

the alkali metal salts thereof; and

wherein n is greater than 5 up to 3×

10⁶ and the polymer exhibits a degree of substitution at R₅, R₆ and R₇ of greater than 0 up to 3;

(b) a compartment formed by the shaped wall, said compartment containing a drug formulation selected from the group consisting of locally and systemically acting physiologically and pharmacologically acceptable drugs;

(c) a passageway in the wall communicating with the compartment and the exterior of the device for dispensing drug from the device; and

(d) wherein in operation, when the device is dispensing the drug to the animal, fluid from the environment is imbided 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 forming a solution containing drug which is dispensed through the passageway at a controlled rate, with the device substantially maintaining its physical and chemical integrity in the presence of the drug and solution thereof during the dispensing period over a prolonged time.

2. The osmotic device for dispensing the drug according to claim 1 wherein the composition contains from 0.01 parts to 50 parts of polymer (2) for 100 parts of shaped wall.

3. The osmotic device for dispensing the drug according to claim 1 wherein the compartment is formed by the shaped wall surrounding and defining an internal space, which space houses with the drug an osmotically effective compound that produces an osmotic pressure in the compartment in excess of 8 atmospheres.

4. The osmotic device for dispensing the drug according to claim 1 wherein the shaped wall contains a different polymer selected from the polymer (2) consisting of hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, carboxymethyl cellulose and carboxymethyl ethylcellulose.

5. The osmotic device for dispensing the drug according to claim 1 wherein the device is sized, shaped and adapted for dispensing drug in the gastrointestinal tract.

6. The osmotic device for dispensing the drug according to claim 1 wherein the device is sized, shaped and adapted for insertion and dispensing drug in the anal canal.

8. The osmotic device for dispensing the drug according to claim 1 wherein the compartment also houses an osmotically effective compound that produces an osmotic pressure in the compartment in excess of 8 atmospheres when the device is in the environment of use.

9. The osmotic device for dispensing the drug according to claim 1 wherein the device is sized, shaped and adapted for dispensing drug in the gastrointestinal tract.

10. The osmotic device for dispensing the drug according to claim 1 wherein the device is sized, shaped and adapted for insertion and dispensing drug in the anal canal.

7. An osmotic device for dispensing a drug to an animal environment of use comprising:

(a) a shaped wall that substantially maintains its physical and chemical integrity during the controlled dispensing of a drug, said wall a composition comprising a polymer that is permeable to the passage of an external fluid and substantially impermeable to the passage of drug, said polymer having the following formula;

##STR5## wherein R₁, R₂ and R₃ are a member independently selected from the group consisting of hydrogen;

alkyl;

alkenyl;

amino;

alkanoyl;

alkanoyl substituted with a member selected from the group consisting of alkoxy, halogen, hydroxyl, alkanoyl, carboalkyl, carboalkoxy and cyanoalkoxy;

aroyl, aroyl substituted with a member selected from the group consisting of hydroxyl, carboxyl, carboalkyl and cyano;

benzyl;

carboalkyl;

carboxyalkyl;

dialkoxyalkyl;

dithiocarbonyl;

hydroxyalkyl;

cyanoalkyl;

nitro;

phenyl;

sulfoalkyl;

the alkali metal salts thereof; and

wherein said polymer exhibits a degree of substitution at R₁, R₂, and R₃ of greater than 0 up to 3, and n is greater than 5;

said composition comprising an additional and different wall forming polymer which is a member selected from the group consisting of acylated polysaccharide, acylated starch, poly(vinyl acetate), poly(vinyl alcohol), and cross-linked poly(vinyl acetate);

(b) a compartment formed by the shaped wall, said compartment containing a drug formulation selected from the group consisting of locally and systemically acting drugs;

(c) a passageway in the wall communicating with the compartment and the exterior of the device for dispensing drug from the device; and

(d) wherein in operation, when the device is dispensing drug to the environment of use, fluid from the environment is imbided 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 forming a solution containing drug that is dispensed through the passageway at a controlled rate, with the device substantially maintaining its physical and chemical integrity in the presence of drug and solution thereof during the dispensing period over a prolonged time.