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Methods, formulations, and devices are provided for enhancing drug delivery from a medical device. The method is provided for increasing the rate or quantity of a drug formulation released from an implantable drug delivery device, which method comprises the step of providing a release-modifying agen

Methods, formulations, and devices are provided for enhancing drug delivery from a medical device. The method is provided for increasing the rate or quantity of a drug formulation released from an implantable drug delivery device, which method comprises the step of providing a release-modifying agent within or proximate to the implantable drug delivery device, in a manner effective to inhibit gelation, aggregation, or precipitation of the drug formulation being released from the device. The drug formulation and the release-modifying agent may be stored together in at least one reservoir in the implantable drug deliver device. Alternatively, the release-modifying agent may be stored in one or more reservoirs separate from the drug formulation.

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We claim: 1. An implantable medical device for the storage and controlled release of a drug formulation comprising: a body portion; at least one reservoir located in at least one surface of the body portion and having a plurality of discrete release openings; at least one drug formulation, which co

We claim: 1. An implantable medical device for the storage and controlled release of a drug formulation comprising: a body portion; at least one reservoir located in at least one surface of the body portion and having a plurality of discrete release openings; at least one drug formulation, which comprises at least one drug, disposed within the at least one reservoir; a release-modifying agent disposed within the at least one reservoir and/or within a second reservoir which is separate from the at least one reservoir in which the drug formulation is disposed, wherein the release-modifying agent is selected from the group consisting of a non-volatile, monoprotic organic acid; a non-volatile, polyprotic organic acid; a non-volatile, mono-functional base; and a non-volatile, poly-functional base; one or more reservoir caps closing off the plurality of discrete release openings of the at least one reservoir; at least one reservoir cap support between at least two of the release openings which extends over the at least one drug formulation, wherein said one or more reservoir caps are in part supported by the at least one reservoir cap support; and electrical circuits, a power source, and a controller for disintegrating said reservoir caps to permit release of the drug formulation from the at least one reservoir. 2. The device of claim 1, wherein the drug formulation and the release-modifying agent are both stored in the same at least one reservoir. 3. The device of claim 1, wherein the electrical circuits comprise an input lead and an output lead connected to each of said reservoir caps for disintegrating the reservoir caps by electrothermal ablation. 4. The device of claim 1, wherein the release-modifying agent enhances release of the drug formulation from said at least one reservoir to a physiological environment by inhibiting gelation, aggregation, or precipitation of the drug formulation. 5. The device of claim 4, wherein the physiological environment has a first pH, and wherein the release-modifying agent enhances release of the drug formulation from said at least one reservoir to a physiological environment by imparting a second pH to at least a portion of the physiological environment within or proximate to the at least one reservoir having the drug formulation, the second pH being less than or greater than the first pH. 6. The device of claim 1, wherein the release-modifying agent enhances release of the drug formulation from said at least one reservoir to a physiological environment by (i) altering the hydrophobic or hydrophilic nature of the physiological environment within or proximate to said at least one reservoir having the drug formulation, (ii) binding to hydrophobic or hydrophilic domains of the drug formulation, or (iii) inhibiting oxidation of the drug formulation in the physiological environment. 7. The device of claim 2, wherein the drug formulation is in the form of a solid matrix having pores or interstices. 8. The device of claim 7, wherein the release-modifying agent enhances dissolution of the drug formulation into a physiological liquid by increasing the capillary action of the physiological liquid through the matrix solid or by causing the solid matrix to be crystalline. 9. The device of claim 7, wherein the release-modifying agent is located into the pores or interstices of the solid matrix. 10. The device of claim 7, further comprising one or more excipient materials, wherein the release-modifying agent and the one or more excipients materials are located in the pores or interstices of the solid matrix. 11. The device of claim 10, wherein at least one of the one or more excipient materials is in solid form. 12. The device of claim 10, wherein at least one of the one or more excipient materials comprises a polyethylene glycol or another polymeric material. 13. The device of claim 1, wherein the at least one reservoir further comprises a void volume displacing material. 14. The device of claim 1, wherein the drug formulation is sealed in the at least one reservoir at a reduced pressure, relative to ambient pressure, or with an inert gas, or both at a reduced pressure and with an inert gas. 15. The device of claim 2, wherein the release-modifying agent is provided in the at least one reservoir in the form of one or more first layers and the drug formulation is provided in the at least one reservoir in the form of one or more second layers adjacent to and/or interspersed with the one or more first layers. 16. The device of claim 2, wherein the drug formulation and the release-modifying agent are in the form of a molten solution or suspension. 17. The device of claim 1, wherein the at least one reservoir is a microreservoir. 18. The device of claim 1, having a plurality of discrete reservoirs provided in an array on a surface of the body portion and containing the drug formulation. 19. The device of claim 1, wherein the body portion is in the form of a chip, a disk, a tube, or a sphere. 20. The device of claim 1, wherein the body portion comprises silicon, a metal, a polymer, a ceramic, or a combination thereof. 21. The device of claim 1, wherein the drug formulation comprises an amino acid, a peptide, or a protein. 22. The device of claim 1, wherein the release-modifying agent comprises citric acid. 23. The device of claim 1, wherein the drug formulation comprises human parathyroid hormone, a leutenizing hormone-releasing hormone, a gonadotropin-releasing hormone, a natriuretic peptide, exenatide, pramlintide, a tumor necrosis factor (TNF) inhibitor, an analog thereof, or a combination thereof. 24. The device of claim 1, wherein the release-modifying agent comprises at least one non-volatile, monoprotic or polyprotic organic acid. 25. The device of claim 1, wherein the release-modifying agent comprises at least one non-volatile, mono-or poly-functional base. 26. The device of claim 1, wherein the volume of the at least one reservoir is between 1 nL and 500 μL. 27. An implantable medical device for the storage and controlled release of a drug formulation comprising: a body portion; a plurality of discrete reservoirs located in at least one surface of the body portion, each reservoir having two or more release openings; at least one drug formulation, which comprises a drug, disposed within at least a portion of the plurality of discrete reservoirs; a plurality of discrete reservoir caps closing off the release openings of each of the reservoirs; a reservoir cap support between said two or more release openings which extends over the at least one drug formulation, wherein at least two of said discrete reservoir caps are in part supported by the at least one reservoir cap support; activation means for selectively disintegrating two or more of the reservoir caps to permit release of the drug formulation from one of the plurality of discrete reservoirs; a release-modifying agent disposed within the at least a portion of the plurality of discrete reservoirs, wherein the release-modifying agent is selected from the group consisting of a non-volatile, monoprotic organic acid; a non-volatile, polyprotic organic acid; a non-volatile, mono-functional base; and a non-volatile, poly-functional base. 28. The device of claim 27, wherein the release-modifying agent comprises citric acid. 29. The device of claim 27, wherein the drug formulation comprises human parathyroid hormone, a leutenizing hormone-releasing hormone, a gonadotropin-releasing hormone, a natriuretic peptide, exenatide, pramlintide, a tumor necrosis factor (TNF) inhibitor, an analog thereof, or a combination thereof. 30. The device of claim 27, wherein the drug formulation is in the form of a solid matrix having pores or interstices. 31. The device of claim 30, wherein the release-modifying agent is located within the pores or interstices of the solid matrix. 32. The device of claim 30, further comprising one or more excipient materials located in the pores or interstices of the solid matrix. 33. The device of claim 32, wherein at least one of the one or more excipient materials is in solid form. 34. The device of claim 32, wherein at least one of the one or more excipient materials comprises a polymeric material. 35. The device of claim 34, wherein the one or more excipient materials comprises a polyethylene glycol. 36. The device of claim 27, wherein the drug formulation is sealed in the plurality of discrete reservoirs at a reduced pressure relative to ambient pressure, with an inert gas, or both at a reduced pressure and with an inert gas. 37. The device of claim 27, wherein the volume of each discrete reservoir is between 1 nL and 500 μL. 38. An implantable medical device for the storage and controlled release of a drug formulation comprising: a body portion; a plurality of discrete microreservoirs located in the body portion, each reservoir having two or more discrete release openings separated by a reservoir cap support; a drug which comprises a protein or peptide, disposed within each of the plurality of discrete microreservoirs, wherein the drug is in a lyophilized porous solid form; and a release-modifying agent which comprises a non-volatile, water soluble organic acid or conjugate base, the release modifying agent being disposed with the drug within each of the plurality of discrete microreservoirs. 39. The implantable medical device of claim 38, wherein the water soluble organic acid is selected from the group consisting of citric acid, acetic acid, succinic acid, fumaric acid, pivalic acid, lactic acid, tartaric acid, amino acids, and combinations thereof. 40. The implantable medical device of claim 38, wherein the water soluble organic acid is mixed with the drug in the lyophilized porous solid form. 41. The implantable medical device of claim 40, wherein each of the plurality of microreservoirs further comprises a void volume displacing material infiltrating the pores of the lyophilized porous solid form. 42. The implantable medical device of claim 38, further comprising: a plurality of discrete reservoir caps closing off said plurality of discrete release openings; and electrical circuitry, a power source, and a controller for selectively disintegrating each of the reservoir caps to permit release of the drug formulation from the microreservoirs. 43. The implantable medical device of claim 38, wherein the body portion comprises two or more substrate portions bonded together, one of said substrate portions comprising the at least one reservoir cap support.