Erodible device comprising surfactant for modifying the rate of erosion of the device

• US 4,322,323 A
• Filed: 12/01/1980
• Issued: 03/30/1982
• Est. Priority Date: 12/01/1980
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Capozza, Richard C.
• Primary Examiner(s): Michl, Paul R.
• Application Number:
  US06/211,510
• Time in Patent Office: 484 Days
• Field of Search: 260/18 R, 260/18 TN, 525/1, 525/3, 525/4, 525/5, 525/6, 528/370, 528/371, 528/403, 528/405, 528/406, 528/425
• US Class Current: 514/772
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: C08K 5/098 Metal salts of carboxylic acids

Abstract

An erodible device is disclosed for delivering an agent to an environment of use. The device comprises (1) a structure sized and adapted for placement in an environment of use, the structure comprising a poly(orthoester) or a poly(orthocarbonate) having a repeating mer consisting of hydrocarbon radical and a symmetrical dioxycarbon unit of the general formula: ##STR1## wherein R₁ is a multivalent hydrocarbon radical, R₂ and R₃ are hydrocarbon radicals with at least one of R₂ or R₃ bonded to the dioxycarbon through an oxygen covalent bond, (2) a beneficial agent, and (3) a surfactant erosion rate modifier. The devices are useful for delivering numerous agents to many environments. A composition also is disclosed comprising a poly(orthoester) or a poly(orthocarbonate), and a surfactant.

Claims

1. A device for delivering a beneficial agent at a controlled rate over a prolonged period of time, wherein the device comprises (a) a shaped body sized and adapted for delivering an agent to an environment of use, the body formed of an erodible release rate controlling material, which material comprises a polymer of the formula:

##STR4## wherein, R₁ is a member selected from the group consisting of divalent, trivalent and titravalent radicals consisting of alkylene of 1 to 10 carbons;

alkenylene of 2 to 10 carbons;

alkyleneoxy of 2 to 6 carbons;

cycloalkylene of 3 to 7 carbons;

cycloalkylene of 3 to 7 carbons substituted with an alkyl of 1 to 7 carbons, alkoxy of 1 to 7 carbons, alkenyl of 2 to 7 carbons and alkylene of 1 to 10 carbons;

cycloalkenylene of 4 to 7 carbons;

cycloalkenylene of 4 to 7 carbons substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons, an alkenyl of 2 to 7 carbons, and an alkylene of 1 to 7 carbons;

arylene of 6 to 12 carbons;

arylene of 6 to 12 carbons substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons, and an alkenyl of 2 to 7 carbons;

R₂ and R₃ are selected from the group consisting of alkyl of 1 to 7 carbons;

alkenyl of 2 to 7 carbons, alkoxy of 1 to 7 carbons;

alkylene of 1 to 7 carbons, alkenylene of 2 to 7 carbons;

alkyloxy of 1 to 7 carbons;

alkenyloxy of 2 to 7 carbons;

alkyleneoxy of 1 to 7 carbons;

alkenyleneoxy of 2 to 7 carbons;

aryloxy of 6 to 12 carbons;

aralkyleneoxy of 8 to 12 carbons;

aralkenyleneoxy of 8 to 12 carbons;

oxa;

OR₁ O wherein R₁ is as defined above;

a heterocyclic ring of 5 to 8 carbons and oxygen atoms formed when R₂ and R₃ are taken together;

a heterocyclic ring of 5 to 8 carbon and oxygen atoms substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons and an alkenyl of 2 to 7 carbons formed when R₂ and R₃ are taken together;

a fused polycyclic ring of 8 to 12 carbon and oxygen atoms formed when R₂ and R₃ are taken together;

a fused polycylic ring of 8 to 12 carbons and oxygen atoms substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons, and an alkenyl of 2 to 7 carbons;

wherein at least one of R₂ and R₃ is selected from the group consisting of alkoxy, alkenyloxy, and OR₁ O; and

R₂ and R₃ are taken together a member selected from the group of heterocyclic and fused polycyclic rings having at least one oxygen atom in the ring; and

wherein n is greater than 10;

(b) a beneficial agent in the body; and

(c) a surfactant selected from the group consisting of anionic, cationic and nonionic surfactants.

3. A device for delivering the beneficial agent at a controlled rate over a prolonged period of time according to claim 1, wherein the anionic surfactant is a member selected from the group consisting of sodium oleate, sodium lauryl sulfate, sodium cetyl sulfate, sodium stearyl sulfate, sodium alkylbenzene sulfonate, dralkyl sulfosuccinate, dioctylester of sodium sulphosuccinic acid;

and sodium salt of alkylated aryl polyether sulfate.

4. A device for delivering the beneficial agent at a controlled rate over a prolonged period of time according to claim 1, wherein the cationic surfactant is a member selected from the group consisting of lauryldimethylbenzylammonium chloride, diisobutylphenoxyethoxyethyldimethyl benzylammonium chloride, alkyldimethylbenzylammonium chloride, laurylisoquinolinium bromide, cetylethyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, and ethanolated alkyl guanidine complex.

5. A device for delivering the beneficial agent at a controlled rate over a prolonged period of time according to claim 1, wherein the nonionic surfactant is a member selected from the group consisting of dodecylphenoxypolyethoxyethanol, isooctylphenoxypolyethoxythanol, polyoxyethylene sorbitan mololaurate, polyoxyethylene stearate, polyoxyethylene laurylalcohol and polyglycol ether of alkylphenol.

6. The device for delivering the beneficial agent according to claim 1 wherein the beneficial agent is a member selected from the group consisting of a pesticide, herbicide, germicide, biocide, algicide, fungicide, insecticide and rodenticide.

2. A composition of matter comprising a polymer of the general formula:

##STR5## wherein, R₁ is a member selected from the group consisting of a divalent, trivalent and tetravalent radicals consisting of alkylene of 1 to 10 carbons;

alkenylene of 2 to 10 carbons;

alkyleneoxy of 2 to 6 carbons;

cycloalkylene of 3 to 7 carbons;

cycloalkylene of 3 to 7 carbons substituted with an alkyl of 1 to 7 carbons, alkoxy of 1 to 7 carbons, alkenyl of 1 to 7 carbons, and an alkylene of 1 to 10 carbons;

cycloalkenylene of 4 to 7 carbons, cycloalkenylene of 4 to 7 carbons substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons, an alkenyl of 2 to 7 carbons, and an alkylene of 1 to 7 carbons;

arylene of 6 to 12 carbons;

arylene of 6 to 12 carbons substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons, and an alkenyl of 2 to 7 carbons;

R₂ and R₃ are selected from the group consisting of alkenyl of 2 to 7 carbons;

alkoxy of 1 to 7 carbons;

alkylene of 1 to 7 carbons;

alkenylene of 2 to 7 carbons;

alkyleneoxy of 1 to 7 carbons;

aryloxy of 6 to 12 carbons;

aralkyleneoxy of 8 to 12 carbons;

alkenyleneoxyl of 2 to 7 carbons;

aralkenyleneoxy of 8 to 12 carbons;

OR₁ O wherein R₁ is as defined;

a heterocyclic ring of 5 to 8 carbons and oxygen atoms formed when R₂ and R₃ are taken together;

a heteroxcyclic ring of 5 to 8 carbon and oxygen atoms substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons and an alkenyl of 2 to 7 carbons formed when R₂ and R₃ are taken together;

a fused polycyclic ring of 8 to 12 carbon and oxygen atoms formed when R₂ and R₃ are taken together;

a fused polycyclic ring of 8 to 12 carbon and oxygen atoms substituted with an alkyl of 1 to 7 carbons, an alkoxy of 1 to 7 carbons and an alkenyl of 2 to 7 carbons;

n is greater than 10; and

from 0.001% to 5% by weight of a surfactant selected from the group consisting of anionic, cationic and nonionic surfactants.

7. A device for delivering a drug at a controlled rate for a prolonged period of time, wherein the device comprises:

(a) a matrix sized, shaped and adpated for delivering a drug to a biological enviornment, the body formed of a bioerodible drug release rate controlling polymer of the formula;

##STR6## wherein R₁ is a member selected from the group consisting of a divalent, trivalent and tetravelent radicals consisting of alkylene of 1 to 10 carbon atoms;

alkenylene of 2 to 10 carbon atoms;

alkyleneoxy of 2 to 6 carbon atoms;

cycloalkylene of 3 to 7 carbon atoms;

cycloalkylene of 3 to 7 carbon atoms substituted with an alkyl of 1 to 7 carbon atoms, an akloxy of 1 to 7 carbon atoms, alkenyl of 2 to 7 carbon atoms and an aklylene of 1 to 10 carbon atoms;

cycloalkenylene of 4 to 7 carbon atoms;

cycloalkenylene of 4 to 7 carbon atoms substituted with an alkyl of 1 to 7 carbon atoms, an alkoxy of 1 to 7 carbon atoms, an alkenyl of 2 to 7 carbon atoms and an alkylene of 1 to 10 carbon atoms;

arylene of 6 to 12 carbon atoms; and

arylene of 6 to 12 carbons atoms, substituted with an alkyl of 1 to 7 carbon atoms, and alkylene of 1 to 10 carbon atoms, and an alkenyl of 2 to 7 carbon atoms; and

wherein R₂ and R₃ are taken together to form a heterocyclic ring having from 1 to 2 oxygen atoms positioned at R₂ and R₃ with the ring a member selected from the group consisting of tetrahydrofuranyl, dihydrofuranyl, dihydrofuranyl ocanyl, oxepanyl, dihydrodioxanyl, dioxolanyl, dioxanyl, dioxepanyl, dioxocanyl and dioxonanyl; and

n is greater than 10;

(b) a drug in the matrix selected rom the group consisting of locally and systemically acting drugs; and

(c) a surfactant in the matrix, which surfactant is selected from the group consisting of anionic, nonionic and cationic surfactants.

8. A device for delivering a drug at a controlled rate according to claim 7 wherein the drug is a member selected from the group consisting of gastrointestional, hypnotic, sedative, psychic energizer, tranquilizer, anticonvulsant, antiparkinson, muscle relaxant, analgesic, antipyretic, antiinflammatory, anesthetic, antispasmodic, antimicrobial, antiviral, antiulcer, hormonal, sympathomimetic, duiretic, contraceptive and ophthalmic drugs.