Pulsatile drug delivery system

• US 4,723,958 A
• Filed: 05/23/1986
• Issued: 02/09/1988
• Est. Priority Date: 05/23/1986
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Royce, Alan E., Pope, David G.
• Primary Examiner(s): Truluck, Dalton L.
• Assistant Examiner(s): Whelton, Denise
• Application Number:
  US06/866,415
• Time in Patent Office: 627 Days
• Field of Search: 604/890-893, 604/93, 604/131, 604/140, 424/422, 424/423, 424/438
• US Class Current: 604/890.1
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50

Abstract

There is provided a novel drug delivery system which provides for intermittent drug delivery with readily adjustable intervals between drug delivery pulses. This is accomplished by providing a multilayer device in which layers of active drug are readily expandable or erodable when contacted with the environment in which the drug is to be administered. The drug layer is alternated with an inert layer and a multiplicity of such layers are contained within a tube impervious to such environment but provided with an opening into such environment. The multiplicity of such layers is driven along the length of such tube towards the opening. The interval between pulses is determined by the rate the layers are driven along the tube and the sizes of the layers. The duration of the pulse is determined by the rate of expansion or dispersion of the active layer into the environment, wherein the rate of expansion or dispersion is greater than the rate the layers are driven along the tube.

Claims

1. A pulsatile drug delivery system which comprises an elongated container impervious to environmental fluids with an opening end and a driven end with an opening from the inside of the container to the environment at the opening end and a constant driving force operating at the driven end in a direction towards the opening end;

a multiplicity of layers arranged lengthwise inside the container substantially filling the inside cross-section of the container and situated between the opening and the constant driving force with an expandable layer closest to the opening end containing one or more of a material which is therapeutically or nutritionally beneficial to be dispensed through the opening into the environment upon contact with the fluids of the environment and the layer adjacent thereto being a spacer layer inert to the fluids of the environment and the remainder of the multiplicity of layers alternating between the expandable layer and the spacer layer and wherein the rate of the dispensing of the expandable layer into the environment is greater than the rate of the constant driving force.

2. The pulsatile drug delivery system of claim 1 wherein the expandable layer is dispensed through the opening by dispersion into the fluids of the environment.

3. The pulsatile drug delivery system of claim 1 wherein the expandable layer is dispensed through the opening by expansion due to the absorption of the fluids of the environment.

4. The pulsatile drug delivery system of claim 1 wherein the expandable layer is one layer of a material which is therapeutically or nutritionally beneficial and a separate layer of a material expandable upon contact with the environment wherein the drug containing material is dispensed through the opening by the force exerted by the expandable layer upon the layer containing the therapeutically or nutritionally beneficial material.

5. The pulsatile drug delivery system of claim 1 wherein the layers are of varying sizes materials and dispensing characteristics such that a non-uniform series of pulses is provided.

6. The pulsatile drug delivery system of claim 1 wherein the expandable layer contains a polymeric material which expands upon contact with the fluids of the environment.

7. The pulsatile drug delivery system of claim 6 wherein the polymeric material is xanthan gum, carboxymethylcellulose, methyl cellulose, alginate, amylose, amylopectin, carboxymethyl starch, acrylics or methyacrylics.

8. The pulsatile drug delivery system of claim 1 wherein the constant driving force is provided by an osmotic pump.

9. The pulsatile drug delivery system of claim 8 wherein the osmotic pump is incorporated within the container of the pulsatile drug delivery system.

10. The pulsatile drug delivery system of claim 1 wherein the opening end of the container is provided with a storage area for the spacer layers.

11. The pulsatile drug delivery system of claim 10 wherein the opening is a circumferential series of spaces through the container.

12. The pulsatile drug delivery system of claim 1 wherein the opening comprises the entire cross-section of the container.

13. The pulsatile drug delivery system of claim 1 which is for oral administration.

14. The pulsatile drug delivery system of claim 13 which is for oral administration to ruminant animals.

15. The pulsatile drug delivery system of claim 14 which is provided with densifying agents or variable geometry to cause the retention of the system in the rumen.

16. The pulsatile drug delivery system of claim 1 which is parenterally implanted.

17. The pulsatile drug delivery system of claim 16 wherein the parenteral implant is subcutaneous.

18. The pulsatile drug delivery system of claim 1 wherein the drug being administered is a therapeutic agent.

19. The pulsatile drug delivery system of claim 18 wherein the therapeutic agent is ivermectin.

20. The pulsatile drug delivery system of claim 1 wherein the drug being administered is a supplemental nutrient material.