Osmotic system with laminated wall comprising structurally different semipermeable lamina

• US 4,116,241 A
• Filed: 12/15/1976
• Issued: 09/26/1978
• Est. Priority Date: 02/02/1976
• 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): Michell, Robert W.
• Assistant Examiner(s): Stremcha, Jerome D.
• Application Number:
  US05/750,773
• Time in Patent Office: 650 Days
• Field of Search: 128/260, 128/268, 128/272, 128/130, 424/19, 424/21, 424/22, 424/28, 222/95, 222/386.5
• US Class Current: 604/892.1
• 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

Abstract

An osmotic system for delivering a beneficial agent to an environment of use is disclosed. The system comprises a laminate surrounding a compartment and has a passageway through the laminate for releasing agent from the compartment. The laminate comprises at least two laminae; one consisting of a semipermeable, polymeric material that is permeable to the passage of an external fluid and maintains its physical and chemical integrity in the environment of use, and one consisting of a semipermeable polymeric material that is permeable to the passage of fluid, substantially impermeable to the passage of agent and maintains its physical and chemical integrity in the presence of agent. The compartment comprises an active agent that is either soluble in the external fluid and exhibits an osmotic pressure gradient across the laminate against the fluid, or the agent has limited solubility in the fluid and it is mixed with an osmotically effective compound that is soluble in the fluid and exhibits an osmotic pressure gradient across the laminate against the fluid. In operation, agent is released from the system by fluid being imbibed through the laminate into the compartment at a rate controlled by the permeability of the laminate and the osmotic pressure gradient across the laminate producing a solution containing agent, or a solution of compound containing agent which solution in either operation is released through the passageway at a controlled and continuous rate over a prolonged period of time.

Claims

1. An oral osmotic system sized and adapted for the controlled administration of drug to an animal, said system comprising:

a. a shaped laminated wall comprising (1) a lamina formed of a material that maintains its physical and chemical integrity in the presence of fluid, drug and during the dispensing of drug, and is permeable to the passage of fluid and impermeable to the passage of drug, said lamina formed of a material having the general formula;

##STR4## wherein R₅ is a member selected from the group consisting of hydroxyl, alkoxy, alkylcarbonate, alkylcarbamate, alkylsulfonate, alkylsulfamate and acyloxy, and wherein n is a positive number greater than 5 and at least one R is acyloxy, said lamina laminated to (2) a lamina formed of a different material that maintains its physical and chemical integrity in the presence of fluid, drug and during the dispensing of drug, and is permeable to the passage of fluid and impermeable to the passage of drug, said lamina formed of the different material selected from the general formula;

##STR5## wherein R₅ is a member selected from the group consisting of hydroxyl, alkoxy, alkylcarbonate, alkylcarbamate, alkylsulfonate, alkylsulfamate, and acyloxy, and wherein n is a positive number greater than 5 and at least one R is acyloxy;

the wall surrounding and forming,

b. a compartment containing a member 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 system for administering drug from the system; and

,

d. wherein in operation when the system is in the animal fluid therefrom is imbibed through the laminated wall into the compartment in a tendency towards osmotic equilibrium at a rate determined by the permeability of the laminated wall and the osmotic pressure gradient across the laminated wall thereby continuously dissolving drug that is administered according to the following equation;

space="preserve" listing-type="equation">h.sub.T /kπ

.sub.T = h.sub.1 /kπ

.sub.1 + h.sub.2 /kπ

.sub.2

wherein h_T is the thickness of the laminated wall, h₁ is the thickness of lamina (1,) h₂ is the thickness of lamina 2, kπ

_T is the osmotic pressure of drug in the compartment times the permeability of the laminated wall to fluid, kπ

₁ is the osmotic pressure of drug in the compartment times the permeability of lamina (1) to fluid and kπ

₂ is the osmotic pressure of drug in the compartment times the permeability of lamina (2) to fluid, through the passageway at a controlled and continuous rate over a prolonged period of time.

2. The osmotic system for the controlled administration of drug according to claim 1, wherein the acyloxy in lamina (1) is a member selected from the group consisting of alkanoxyloxy, alkenyloxy and aroyloxy and the degree of substitution on each anhydroglucose unit is greater than from 0 up to 3.

3. The osmotic system for the controlled administration of drug according to claim 1, wherein the acyloxy in lamina (2) is a member selected from the group consisting of formyloxy, acetyloxy, propionyloxy, valeryloxy, heptanoyloxy, octanoyloxy, underanoyloxy, lauroyloxy, palmitoyloxy, steroyloxy, oleoyloxy, acryloxyloxy, methacryloyloxy, crotomyloxy, butenoyloxy, benzoyloxy, phenylacetyloxy, cinnamoyloxy, naphthoyloxy, ethoxybenzyloxy, and furoyloxy.

4. The osmotic system for the controlled administration of drug according to claim 1, wherein the material forming lamina (1) is a member selected from the group consisting of cellulose acetate acetoacetate dimethoxyethylcellulose acetate, cellulose acetate benzoate, cellulose acetate dimethylsulfamate, ethylcellulose dimethylsulfamate, cellulose acetate methylcarbonate, cellulose acetate ethylcarbonate, cellulose acetate methylcarbamate and cellulose acetate ethylcarbamate.

5. The osmotic system for the controlled administration of drug according to claim 1, wherein the material forming lamina (2) is a member selected from the group consisting of ethylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethyl methylcellulose, hydroxypropyl methylcellulose, ethylhydroxy ethylcellulose, and hexylpropyl cellulose.

6. The osmotic system for the controlled administration of drug according to claim 1, wherein the drug is present in the compartment mixed with an osmagent, and lamina (1) is formed of cellulose acetate having an acetyl content of 35 to 44.8%, and lamina (2) is formed of cellulose acetate having an acetyl content of 21 to 35%.

7. The osmotic system for the controlled administration of drug to an animal according to claim 1, wherein lamina (2) is formed of a member selected from the group consisting of cellulose triacetate, cellulose trivalerate, cellulose trilaurate, cellulose tripalmitate cellulose trisuccinate, cellulose triheptylate, cellulose tricaprylate, cellulose trioctanoate and cellulose tripropionate.

8. The osmotic system for the controlled administration of drug to an animal according to claim 1, wherein lamina (1) is formed of a member selected from the group consisting of cellulose disuccinate, cellulose dipalmitate, cellulose dioctanoate, cellulose dicaprylate and cellulose dipentanoate.

9. The osmotic system for the controlled administration of drug according to claim 1, wherein lamina (1) and lamina (2) exhibit a decreased permeability to the passage of fluid as the size is increased of the substituting group forming said laminae.

10. The osmotic system for the controlled administration of drug according to claim 1, wherein the compartment contains 0.05 ng to 5 grams of a drug that can be orally administered to produce a beneficial result.

11. The osmotic system for the controlled administration of drug according to claim 1, wherein lamina (1) is laminated to lamina (2) by successive air suspension lamination using an organic solvent selected from the group consisting of an alcohol, ketone, ester, ether, aliphatic hydrocarbon, halogenated hydrocarbon, cycloaliphatic aromatic, a heterocyclic, and solvent mixtures thereof.