Two-Stage Microchip Drug Delivery Device and Methods
Drug delivery devices and methods of controlled drug delivery to a patient are provided. The drug delivery device may include one or two microchip elements, each of which has a body portion with one or more drug release apertures in fluid communication with at least one containment reservoir. The drug release apertures are closed off by one or more reservoir caps which can be electrically activated to open the drug release apertures. The drug delivery device also includes (i) a drug formulation disposed in the at least one containment reservoir, and (ii) at least one drug-permeable membrane. In some cases, an outer housing is spaced a distance from an exterior wall of the body portion of the microchip element, the outer housing includes the at least one drug-permeable membrane, and a depot space is defined between the drug-permeable membrane and the exterior wall of the body portion of the microchip element.
1 . A method of controlled drug delivery to a patient, comprising:
implanting a drug delivery device in the patient, wherein the drug delivery device comprises:
a first microchip element which comprises a body portion defining at least one containment reservoir therein, wherein the body portion has an exterior wall having one or more drug release apertures in fluid communication with the at least one containment reservoir, the one or more drug release apertures being closed off by one or more corresponding reservoir caps configured to be electrically activated to unclose the one or more drug release apertures;
a drug formulation, which comprises a drug, disposed in the at least one containment reservoir; and
a drug-permeable membrane secured next to the exterior wall of the body portion of the first microchip element and outside of the at least one containment reservoir;
activating at least one of the one or more reservoir caps to permit interstitial fluid to contact the drug in the at least one containment reservoir corresponding to the activated one or more reservoir caps;
releasing the drug from the at least one containment reservoir corresponding to the activated one or more reservoir caps into a drug depot space adjacent to the drug-permeable membrane; and
releasing the drug from the drug depot space into the patient by diffusion through the drug-permeable membrane.
2 . The method of claim 1 , wherein the release of the drug from the at least one containment reservoir into the drug depot space comprises swelling of a water swellable charge material to eject the drug from the containment reservoir.
3 . The method of claim 1 , wherein the drug delivery device further comprises an outer housing wall secured in a position next to, and spaced a distance from, the exterior wall of the body portion of the microchip element, wherein the outer housing wall comprises the drug-permeable membrane.
4 . The method of claim 1 , wherein the exterior wall is in direct mechanical contact with the drug permeable membrane before activation of the one or more reservoir caps.
5 . The method of claim 1 , wherein the drug is released from the activated at least one containment reservoir by a process comprising swelling of the drug formulation and/or by an extrusion process.
6 . The method of claim 1 , wherein:
the at least one containment reservoir is in the form of a plurality of microreservoirs;
the one or more drug release apertures are in the form of a plurality of drug release apertures in fluid communication with the plurality of microreservoirs;
the one or more corresponding reservoir caps are in the form of a plurality of the corresponding reservoir caps which are configured to be ruptured by electrothermal ablation to open the plurality of drug release apertures.
7 . The method of claim 6 , wherein:
the drug formulation, together with a water swellable charge material, is disposed in each of the microreservoirs; and
following activation of one or more of the plurality of reservoir caps, interstitial fluid in the patient is imbibed by the water swellable charge material in the microreservoirs corresponding to the activated one or more reservoir caps, effective to cause the charge material to swell and eject the drug out of said microreservoirs through the drug release apertures.
8 . The method of claim 1 , wherein the drug comprises a hormone.
9 . The method of claim 1 , wherein the drug comprises a contraceptive hormone.
10 . The method of claim 1 , wherein the drug comprises levonorgestrel.
11 . The method of claim 1 , wherein the drug delivery device further comprises a second microchip element and a second exterior wall which comprises a second drug-permeable membrane defining a second drug depot space.
12 . The method of claim 11 , wherein the drug delivery device further comprises a hermetic enclosure, wherein (i) the hermetic enclosure is not disposed between the microchip element and the second microchip element, and (ii) the first and second microchip elements are disposed adjacent one another with their exterior walls facing in opposite directions.
13 . The method of claim 11 , wherein the first and second microchip elements are located a single side of the drug delivery device and electronic components are located on an opposing side of the first and second microchip elements.
14 . The method of claim 13 , wherein the drug delivery device further comprises a hermetic enclosure fixed to the first and second microchip elements on a side opposed from the depot space.
15 . The method of claim 1 , wherein the drug delivery device further comprises:
a second microchip element which comprises a second body portion defining at least one containment reservoir therein, wherein the second body portion has an exterior wall having one or more drug release apertures in fluid communication with the at least one containment reservoir, the one or more drug release apertures being closed off by one or more corresponding reservoir caps configured to be electrically activated to unclose the one or more drug release apertures;
a drug formulation, which comprises a drug, disposed in the at least one containment reservoir of the second microchip element; and
a second drug-permeable membrane secured next to the exterior wall of the body portion of the second microchip element, wherein the device is configured, upon activation of the one or more reservoir caps of the second microchip element, to release the drug therefrom by diffusion through the second drug-permeable membrane.
16 . The method of claim 15 , wherein the drug delivery device further comprises:
a second outer housing wall, which comprises the second drug permeable membrane, which is secured in a position next to, and spaced a distance from, the exterior wall of the body portion of the second microchip element, to define a second depot space between the second drug-permeable membrane and the exterior wall of the body portion of the second microchip element.
17 . The method of claim 16 , further comprising a hermetic enclosure disposed between the first microchip element and the second microchip element, wherein hermetic enclosure contains electronic components configured for electrical activation of the reservoir caps of the first microchip element and the second microchip element.
18 . The method of claim 1 , wherein the patient is a human.
19 . The method of claim 1 , wherein, upon depletion of the drug in the depot space, additional reservoir caps, corresponding to additional containment reservoirs, are activated to replenish the drug in the depot space, as needed to provide a therapeutically effective concentration of the drug in the patient over a desired sustained period.