Transdermal drug delivery patch system, method of making same and method of using same

An integrated monitoring and delivery system comprising:

• a) a delivery and extraction patch comprising:
• i) a first section comprising a first tissue interface layer and a first reservoir for storing a permeant composition to be applied to a tissue membrane, said first tissue interface membrane further comprising a substrate with a first porator array contained on or within said substrate;
• ii) a second section comprising a second tissue interface layer and a second reservoir for collecting an analyte from said tissue membrane for analysis, said second tissue interface membrane further comprising a substrate with a second porator array contained on or within said substrate;
• iii) an adhesive for adhering said patch to said tissue membrane;
• b) a controller for actuating said porator array, thereby forming micropores in said tissue membrane;
• and
• c) an apparatus for analyzing said analyte, said apparatus containing an algorithm to determine a concentration of said analyte and control delivery of said permeant composition based on said analyte concentration.

A flux enhancement device comprising:

• a) an outer wall defining a cell cavity, said outer wall having an edge which bounds said cell cavity and interfaces with a tissue membrane having a micropore, said cell cavity having an opening on at least one end, said opening interfacing with said tissue membrane;
• b) a reservoir defining an inner cavity, said reservoir being contained within said cell cavity and having an opening oriented toward said opening in said cell cavity;
• c) a first compliant membrane spanning a gap between said reservoir and said outer wall at said membrane interface end of said cell cavity;
• and
• d) a second compliant membrane forming a pressure chamber defined by a wall of said reservoir, said outer wall and said first compliant membrane.

A method of delivering a drug to a patient in need thereof, comprising the steps of:

• a) contacting a poration device to a tissue membrane of said patient, said a poration device comprising:
• i) an outer body defining a top of said poration device, said outer body containing a cavity;
• ii) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity;
• and
• iii) a tissue interface layer for contacting a tissue membrane of an animal, said tissue interface layer containing at least one porator, and said tissue interface layer forming the bottom of said poration device;
• b) actuating said poration device to form at least one micropore in said tissue membrane;
• c) removing said poration device from said tissue membrane;
• and
• d) applying a reservoir drug patch to said microporated area of said tissue membrane after poration.

A method of delivering a drug to a patient in need thereof, comprising the steps of:

• a) contacting a poration device to a tissue membrane of said patient, said poration device comprising:
• i) an actuator comprising:
• A) an outer body defining a top of said actuator, said outer body containing a cavity;
• B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity;
• and
• C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;
• ii) said porator array comprising:
• A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;
• B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane;
• and
• C) a release liner removably attached to said bottom surface;
• and
• b) actuating said poration device to form at least one micropore in said tissue membrane;
• c) removing said poration device from said tissue membrane;
• and
• d) applying a reservoir drug patch to said microporated area of said tissue membrane after poration.

A method of delivering a drug to a patient in need thereof, comprising the steps of:

• a) contacting a poration device to a tissue membrane of said patient, said a poration device comprising:
• i) an actuator comprising:
• A) an outer body defining a top of said actuator, said outer body containing a cavity;
• B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity;
• and
• C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;
• ii) said porator array comprising:
• A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;
• B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane;
• and
• C) an extension tab laterally and removably attached to said bottom surface, said extension tab including an adhesive applied on the bottom thereof, thereby allowing said extension tab to remain on said tissue membrane upon removal of said porator array;
• and
• D) a release liner removably attached to said bottom surface;
• b) removing said actuator from said porator array;
• c) removing said porator array from said tissue membrane without removing said extension tab;
• and
• d) applying a reservoir drug patch to said microporated area of said tissue membrane, said reservoir drug patch being attached to said extension tab.

A method for enhancing a flux across a biological membrane comprising the steps of:

• a) adhering a flux enhancement cell to said biological membrane, said flux enhancement cell comprising a compliant portion which interfaces with said biological membrane, a central portion and a reservoir;
• b) applying pressure to said central portion, thereby compressing tissue associated with said biological membrane;
• c) pulling said central portion away from said biological membrane while keeping said flux enhancement cell attached to said biological membrane;
• d) inducing a permeant composition from said reservoir to flow through a pore in said biological membrane;
• e) returning said flux enhancement cell to its original state;
• f) removing said flux enhancement cell from said biological membrane.

A method for enhancing a flux across a biological membrane comprising the steps of:

• a) adhering a flux enhancement cell to said biological membrane, said flux enhancement cell comprising a compliant portion which interfaces with said biological membrane, a central portion and a reservoir;
• b) applying pressure to said central portion, thereby compressing tissue associated with said biological membrane;
• c) pulling said central portion away from said biological membrane while keeping said flux enhancement cell attached to said biological membrane;
• d) reducing pressure in said reservoir, thereby inducing a biological fluid to flow into said reservoir;
• e) returning said flux enhancement cell to its original state;
• f) removing said flux enhancement cell from said biological membrane.

A method of monitoring an analyte extracted from a patient and delivering a permeant composition to said patient, comprising the steps of:

• a) contacting a poration device to a tissue membrane of said patient, said poration device comprising:
• i) an actuator comprising:
• A) an outer body defining a top of said actuator, said outer body containing a cavity;
• B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity;
• and
• C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;
• ii) said porator array comprising:
• A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;
• B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate and a plurality of reservoirs, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane;
• and
• C) a release liner removably attached to said bottom surface;
• b) actuating poration of said tissue membrane using said at least one poration array in said poration device;
• c) extracting an analyte from said microporated tissue membrane by way of said at least one micropore array into a first of said reservoirs;
• d) analyzing said analyte to determine concentration of same within said tissue membrane;
• and
• e) delivering a permeant composition to said tissue membrane by way of said at least one micropore array for a second of said reservoirs.

A method of delivering two or more biologically active compounds to a patient in need thereof by way of a tissue membrane, said method comprising the steps of:

• a) forming at least one micropore in said tissue membrane by contacting a poration device with said tissue membrane and activating said poration device, thereby forming said at least one micropore, said poration device comprising:
• i) a actuator comprising:
• A) an outer body defining a top of said actuator, said outer body containing a cavity;
• B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity;
• and
• C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;
• ii) said porator array comprising:
• A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;
• B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate and a plurality of reservoirs, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane;
• and
• C) a release liner removably attached to said bottom surface;
• b) applying a first compound contained in a first of said reservoir of said poration device to said tissue membrane by way of said at least one micropore;
• and
• c) applying a second compound contained in a second of said reservoirs of said poration device to said tissue membrane by way of said at least one micropore.

A method of facilitating passage of biological compounds across a tissue membrane comprising the steps of:

• a) forming at least one micropore in said tissue membrane by contacting a poration device with said tissue membrane and activating said poration device, thereby forming said at least one micropore, said poration device comprising:
• i) an actuator comprising:
• A) an outer body defining a top of said actuator, said outer body containing a cavity;
• B) a controller board comprising driving electronics and a battery, said controller board being positioned within said cavity;
• and
• C) an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;
• ii) said porator array comprising:
• A) a top surface, with a removable adhesive attached to said top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;
• B) a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate and a plurality of reservoirs, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane;
• and
• C) a release liner removably attached to said bottom surface;
• b) applying a first compound contained in a first said reservoirs of said poration device to said tissue membrane by way of said at least one micropore;
• and
• c) extracting a second compound from said tissue membrane and storing said second compound in a second of said reservoirs in said poration device.

A method of manufacturing a drug delivery patch system comprising the steps of:

• a) assembling an actuator comprising the steps of:
• i) forming an outer body defining a top of said actuator, said outer body containing a cavity;.
• ii) assembling a controller board comprising driving electronics and a battery, and positioning said controller board within said cavity;
• and
• iii) preparing an interface connection port for receiving a porator array, said interface connection port containing an anode and a cathode;
• b) assembling said porator array comprising the steps of:
• i) applying a removable adhesive layer to a top surface, said top surface containing two concentric electrical contact rings for contacting said interface connection port at said anode and said cathode upon removal of said adhesive layer;
• ii) forming a bottom surface comprising a tissue interface membrane, said tissue interface membrane further comprising a substrate with at least one porator contained on or within said substrate, said bottom surface further comprising an adhesive layer for attaching said porator array to a tissue membrane;
• and
• iii) attaching an extension tab laterally and removably to said bottom surface, and applying an adhesive layer to the bottom of said extension tab, thereby allowing said extension tab to remain on said tissue membrane upon removal of said porator array;
• and
• iv) removably attaching a release liner to said bottom surface;
• and
• c) attaching a reservoir patch to said extension tab, said reservoir patch being applied to said microporated area of said tissue membrane after poration.

A method of monitoring an analyte extracted from a patient and delivering a permeant composition to said patient, comprising the steps of:

• a) contacting a delivery and extraction patch to a tissue membrane of said patient;
• b) actuating poration of said tissue membrane using at least one poration array in said delivery and extraction patch;
• c) extracting an analyte from said microporated tissue membrane by way of at least one micropore array;
• d) analyzing said analyte to determine concentration of same within said tissue membrane;
• and
• e) delivering a permeant composition to said tissue membrane by way of at least one micropore array.

A transdermal drug delivery patch system for delivering a drug across a tissue membrane comprising:

• a) an actuator;
• b) a porator array removably connected to said actuator, said porator array comprising at least one microporator which is actuated by said actuator and forms at least one micropore in said tissue membrane;
• and
• c) a reservoir patch, said reservoir patch separate from said porator array and applied to said tissue membrane following formation of said at least one micropore.