Osmotic bursting drug delivery device

• US 4,177,256 A
• Filed: 11/29/1977
• Issued: 12/04/1979
• Est. Priority Date: 04/25/1973
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Michaels, Alan S., Guillod, Mark S.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US05/855,605
• Time in Patent Office: 735 Days
• Field of Search: 128/260, 424/141.6, 424/19-22, 424/32-33, 424/78-83
• US Class Current: 424/427
• CPC Class Codes: A61F 6/14 intra-uterine type
• 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 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/0039 Devices retained in the uterus for a prolonged period, e.g. intrauterine devices for contraception
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants

Abstract

A drug delivery for administering drug to an aqueous body environment at a substantially constant rate. The devices consist essentially of a mixture of drug of specific average particle size dispersed in a polymer of specific water permeability, tensile strength, and Young'"'"'s modulus in specific volume proportions such that the particles are surrounded substantially individually by the polymer. The constancy of the release rate of drug from the devices is governed by the drug particle size and volume proportion of drug in the mixture.

Claims

1. A drug delivery device for administering drug continuously to an aqueous body environment for a prolonged time period at a controlled rate, said device being in the form of a solid, unit body that:

(a) is sized and shaped for placement in the environment; and

(b) consists essentially of a mixture that defines a surface of predetermined area that is exposed to the water in said environment, said mixture consisting essentially of

(i) about 1% to about 50% by volume, of discrete depots 0.1 to 250 microns, surface area average diameter, in size of a drug composition that is an osmotically effective solute, said depots being dispered in

(ii) about 50% to about 99%, by volume, of a polymer such that the depots are surrounded substantially individually by a layer of the polymer, the polymer being substantially impermeable to the drug composition, insoluble in the environment at least during the prolonged time period, and permeable to water and having a tensile strength, Young'"'"'s modulus, and a maximum elongation such that the cohesive strength of said layer is exceeded by the pressure that the depot the layer surrounds is able to generate by imbibing water, whereby when the device is placed in the environment, water is imbibed by the depots in a serially inwardly manner beginning with the depots nearest said surface and said pressure is generated therein, causing the polymer layers surrounding said depots to rupture thereby releasing drug composition therefrom to the environment.

2. The drug delivery device of claim 1 wherein the drug composition consists essentially of a drug that is itself an osmotically effective solute.

3. The drug delivery device of claim 1 wherein the drug composition consists essentially of a drug that is not an osmotically effective solute mixed with a compound that is an osmotically effective solute.

4. The drug delivery device of claim 1 wherein the unit body is made entirely of said mixture.

12. The drug delivery device of claim 1 wherein said environment is a cul-de-sac of the eye.

5. A drug delivery device for releasing drug continuously to an aqueous body environment for a prolonged time period at a controlled rate said device being in the form of a solid unit body that is sized and shaped for placement in the environment and consists essentially of a mixture of (i) about 1% to about 50% by volume of a drug composition that when in aqueous solution exhibits an osmotic pressure of at least about 10 atmospheres and that is in the form of discrete depots having a surface area average diameter, d, of about 0.1 to about 250 microns, wth the proviso that:

##EQU3## wherein Φ

is the volume percent of drug composition in the mixture and (ii) about 50% to about 99% by volume of a polymer that has a permeability to water of about 10^-8 to about 10^-12 g cm/cm² sec cm Hg, a tensile strength of about 200 to about 3000 psi, a Young'"'"'s modulus of about 200 to about 3000 psi and is substantially impermeable to the drug composition and insoluable in the environment at least during the prolonged time period;

the depots being dispersed in the polymer such that the depots are surrounded substantially individually by the polymer.

6. A drug delivery device for releasing drug continuously to an aqueous body environment for a prolonged time period at a substantially constant rate, said device:

(a) being in the form of a solid unit body that is sized and shaped for placement in the environment;

(b) having a surface of predetermined area, A, that is exposed to the water in said environment when the device is placed therein; and

(c) consisting essentially of a mixture of

(i) about 1% to about 35% by volume of drug composition that when in aqueous solution exhibits an osmotic pressure of at least about 10 atm, has a density, ρ

, of about 0.5 to about 8 g/cm³, and is in the form of discrete depots having a surface area average diameter, d, of about 0.1 to about 250 microns, and an average depot-to-depot separation in the mixture of at least about 0.5 microns, with the proviso that ##EQU4## where Φ

is the volume percent of drug composition in the mixture, and (ii) about 65% to about 99% by volume of a polymer that has a permeability to water, k, of about 10^-8 to about 10^-12 g cm/cm² sec cm Hg, a tensile strength, T_s, of about 200 to about 3000 psi, and a Young'"'"'s modulus, Y, of about 200 to about 3000 psi and is substantially impermeable to the drug composition and insoluble in the environment at least during the prolonged time period, and, said rate is proportional to ##EQU5## where ρ

, Φ

, k, A, and d are as defined previously, Δ

π

is the difference between the osmotic pressures of the drug composition in aqueous solution and the environment, and

space="preserve" listing-type="equation">λ

.sup. -λ

.sup.- = 3T.sub.s /Y

wherein T_s and Y are as defined previously, with the proviso that λ

is in the range of 1.02 and 4.0, said depots being dispersed in said polymer such that said depots are encapsulated and surrounded substantially individually by a layer of said polymer.

7. The drug delivery device of claim 6 wherein said average diameter is 1 to 50 microns, said permeability to water is 10^-9 to 10^-10 g cm/cm² sec cm Hg, said tensile strength is 400 to 1500 psi, said Young'"'"'s modulus is 300 to 1500 psi, and the polymer has a maximum elongation of 2000% to 1700%.

8. The drug delivery device of claim 7 wherein the polymer is an ethylene-vinyl acetate copolymer.

9. The drug delivery device of claim 8 wherein the environment is a cul-de-sac of the eye.

10. The drug delivery device of claim 9 wherein the drug is pilocarpine nitrate, diethylcarbamazine citrate, epinephrine bitartrate, or tetracycline hydrochloride.

11. The drug delivery device of claim 6 wherein the device consists entirely of said mixture.