WO2011043736A1

WO2011043736A1 - A passive drug delivery device

Info

Publication number: WO2011043736A1
Application number: PCT/SG2009/000495
Authority: WO
Inventors: Cheng Kuo Vincent Lee; Visit Thaveeprungsriporn
Original assignee: Nitto Denko Corporation
Priority date: 2009-10-09
Filing date: 2009-12-24
Publication date: 2011-04-14
Also published as: SG170622A1

Abstract

A passive drug delivery device (102) is provided. The device may include a microfluidic arrangement (104) and the microfluidic arrangement may include a plurality of micropores (106), each micropore being configured to receive a micropore fluid (108) capable of forming a microscale pathway in a stratum corneum layer of skin; wherein the plurality of micropores may be arranged such that a plurality of microscale pathways may be formed by the micropore fluid received in the plurality of micropores; at least one therapeutic agent reservoir (110) configured to receive a therapeutic agent (112); and at least one microchannel (114) fluidly connecting the plurality of micropores with the at least one therapeutic agent reservoir.

Description

A PASSIVE DRUG DELIVERY DEVICE

Technical Field

[0001] Embodiments relate to a passive drug delivery device and a method of drug delivery.

Background

[0002] Drugs are typically administered either orally or by injection. However, some drugs are completely ineffective or of radically reduced efficacy when orally administered since they are either not absorbed or are adversely affected before entering the blood stream and thus do not possess the desired activity. On the other hand, direct injection of the drug into the blood stream, while assuring no modification of the administered drug, is a difficult, inconvenient and uncomfortable procedure, sometimes resulting in poor patient compliance. Transdermal drug delivery may offer improvements in some of these areas.

[0003] Having said that, in transdermal drug delivery, bio-molecules of medical relevance may not be able to reach the skin surface due to a combination of relative size and their inability to diffuse across the densely packed hydrophobic layers of dead-skin cells or stratum corneum (SC). The overall thickness of the stratum comeum may be relatively thick and in an unbroken state, acts as a very effective seal against interstitial fluid leakage and maintains bio-molecular containment. Summary

[0004] In various embodiments, a passive drug delivery device is provided. The passive drug delivery device may include a microfluidic arrangement, the microfluidic arrangement may include a plurality of micropores, each micropore being configured to receive a micropore fluid capable of forming a microscale pathway in a stratum corneum layer of skin; wherein the plurality of micropores may be arranged such that a plurality of microscale pathways may be formed by the micropore fluid received in the plurality of micropores; at least one therapeutic agent reservoir configured to receive a therapeutic agent; and at least one microchannel connecting the plurality of micropores with the at least one therapeutic agent reservoir.

Brief Description of the Drawings

[0005] In the drawings, like reference characters generally refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of various embodiments. In the following description, various embodiments of the invention are described with reference to the following drawings, in which:

FIGS. 1A and IB show respective top and cross-sectional side views of a passive drug delivery device with one therapeutic agent reservoir according to an embodiment;

FIGS. 2A and 2B show respective top and cross-sectional side views of a passive drug delivery device with one therapeutic agent reservoir and one cleansing agent reservoir arranged on opposite sides of a plurality of micropores according to an embodiment; FIGS. 3A and 3B show respective perspective and top views of a passive drug delivery device with one therapeutic agent reservoir and one cleansing agent reservoir arranged on a same side of a plurality of micropores according to an embodiment;

FIGS. 3C to 3E show respective cross-sectional side views of a passive drug delivery device with one therapeutic agent reservoir and one cleansing agent reservoir arranged on a same side of a plurality of micropores according to an embodiment;

FIGS. 4 A and 4B show respective top and cross-sectional side views of a passive drug delivery device with two different therapeutic agent reservoirs and one cleansing agent reservoir, the two different therapeutic agent reservoirs arranged on one side and the cleansing agent reservoir arranged on another side of a plurality of micropores according to an embodiment;

FIGS. 5 A and 5B show respective perspective and top views of a passive drug delivery device with two different therapeutic agent reservoirs and one cleansing agent reservoir arranged on a same side of a plurality of micropores according to an embodiment;

FIGS. 6 A and 6B show respective top and cross-sectional side views of a passive drug delivery device with four similar therapeutic agent reservoirs and four similar cleansing agent reservoirs, the four similar therapeutic agent reservoirs arranged on one side and the four similar cleansing agent reservoirs arranged on another side of a plurality of micropores according to an embodiment;

FIGS. 7A and 7B show respective top and cross-sectional side views of a passive drug delivery device with four different therapeutic agent reservoirs and four similar cleansing agent reservoirs, the four different therapeutic agent reservoirs arranged on one side and the four similar cleansing agent reservoirs arranged on another side of a plurality of micropores according to an embodiment; and

FIG. 8A shows a cross-sectional side view of a passive drug delivery device with one therapeutic agent reservoir and one cleansing agent reservoir arranged on opposite sides of a plurality of micropores with an adhesive layer positioned around the plurality of micropores and the respective therapeutic agent reservoir and the cleansing agent reservoir and the adhesive layer further positioned between each of the plurality of micropores according to an embodiment; FIG. 8B shows a cross-sectional side view of a passive drug delivery device with one therapeutic agent reservoir and one cleansing agent reservoir arranged on opposite sides of a plurality of micropores with an adhesive layer positioned around the plurality of micropores and the respective therapeutic agent reservoir and the cleansing agent reservoir, the adhesive layer further positioned between each of the plurality of micropores and with a cover layer positioned over the plurality of micropores, the first indicator, the second indicator and the adhesive layer according to an embodiment.

Description

[0006] The following detailed description refers to the accompanying drawings that show, by way of illustration, specific details and embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention. Other embodiments may be utilized and structural, logical, and electrical changes may be made without departing from the scope of the invention. The various embodiments are not necessarily mutually exclusive, as some embodiments can be combined with one or more other embodiments to form new embodiments.

[0007] The word "exemplary" is used herein to mean "serving as an example, instance, or illustration". Any embodiment or design described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments or designs.

[0008] In various embodiments, the efficiency of transdermal drug delivery may be increased, and an alternative transdermal drug delivery device and method are provided which may enhance the delivery of transdermal flux to the stratum corneum.

[0009] In various embodiments, a passive drug delivery device and a method of passive drug delivery may be provided, which may enhance delivery of transdermal flux to the stratum corneum.

[0010] An embodiment provides a passive drug delivery device. The device may include a microfluidic arrangement, the microfluidic arrangement may include a plurality of micropores, each micropore being configured to receive a micropore fluid capable of forming a microscale pathway in a stratum corneum layer of skin; wherein the plurality of micropores may be arranged such that a plurality of microscale pathways may be formed by the micropore fluid received in the plurality of micropores; at least one therapeutic agent reservoir configured to receive a therapeutic agent; and at least one microchannel connecting the plurality of micropores with the at least one therapeutic agent reservoir.

[0011] In an embodiment, the micropore fluid may be a solution or a liquid. The micropore fluid may also be termed as the micropore solution. [0012] In an embodiment, the at least one microchannel may be configured or positioned so as to allow a fluidic connection or a fluidic flow between the plurality of micropores and the at least one therapeutic agent reservoir

[0013] The micropore fluid may be capable of forming a microscale pathway in the stratum comeum layer of the skin by etching the stratum corneum to a predetermined depth when in contact. The depth may be in the range of about 10 μπι to 100 μπι, e.g. about 50 μιη. The size and density of the microscale pathways formed may be controlled by regulating the types, contents and volumes of the micropore fluid.

[0014] Each micropore may be an enclosed portion. Each micropore may be a cylinder with a circular cross-section and with a diameter in the range of about 10 μιη to about 1 mm, e.g. a diameter in the range of about 10 μπι to about 0.8 mm, but not so limited. The micropore may also be a cube with a square cross-section. The micropore may also be a sphere, a pyramid, a tetrahedron, a prism or a cone but not so limited. The micropore may include a cross-section in the shape of a rectangle, an oval, a triangle, a pentagon or of any suitable shape depending on user and design requirements. The depth of each micropore may be in the range of about 10 μηι to about 5 mm, e.g. a depth in the range of about 50 μπι to about 3 mm, but not so limited.

[0015] Each microchannel may be an elongated portion. Each microchannel may be a cylinder with a rectangle cross-section and with a cross-sectional area in the range of about 100 μπι² to 0.5 mm², e.g. with a cross-sectional area in the range of about 100 μπι² to 0.2 mm². Each microchannel may also have a cross-section in the shape of a square, a circle, an oval, a triangle, a pentagon or of any suitable shape depending on user and design requirements. [0016] Each therapeutic agent reservoir may be an enclosed portion. Each therapeutic agent reservoir may be a cylinder, a cube, a sphere, a pyramid, a tetrahedron, a prism, a cone or of any suitable shape depending on user and design requirements.

[0017] The volume of each therapeutic agent reservoir may be in the range of about 0.05 mm³ to about 0.5 cm³, e.g. in the range of about 0.1 mm³ to about 0.3 cm³ but not so limited. In the case of a cubic therapeutic agent reservoir, the dimensions of each therapeutic agent reservoir may be in the range of about 1 mm x 1 mm x 0.05 mm to about 1 cm x 2 cm x 2.5 mm but not so limited. The dimensions of each therapeutic agent reservoir may also depend on the amount of therapeutic agent required by a user and on design requirements.

[0018] The number of micropore(s) may depend on the number of microscale pathways needed to be formed in the stratum corneum of skin. There may be the same or different number of micropores in fluid connection with each microchannel. The number of micropores may be typically more than the number of microchannels and the number of microchannels may be typically more than the number of therapeutic agent reservoir(s). However, the respective number of the micropore(s), the microchannel(s) and the therapeutic agent reservoir(s) may depend on user and design requirements.

[0019] In an embodiment, the microfluidic arrangement further includes at least one therapeutic agent controller disposed between the at least one therapeutic agent reservoir and at least one of the plurality of micropores, the at least one therapeutic agent controller being configured so as to allow flow of the therapeutic agent into at least one of the plurality of micropores upon application of a force, a mechanical pressure or a heat pulse upon the at least one therapeutic agent reservoir from the top. Each therapeutic agent controller may be positioned between each therapeutic agent reservoir and each microchannel and/or between each microchannel and each micropore.

[0020] In an embodiment, the at least one therapeutic agent controller may include a oneway valve which may allow flow of the therapeutic agent in a single direction so as to prevent backward flow of the therapeutic agent.

[0021] In an embodiment, the at least one therapeutic agent controller may include a microchannel with surface treatment of inner sidewalls of one-way valve which may allow flow of the therapeutic agent in a single direction so as to prevent backward flow of the therapeutic agent or a breakable membrane. The therapeutic agent controller may also be influenced by capillary force.

[0022] In an embodiment, the at least one therapeutic agent controller may include gas bubbles which may be confined at a region in the microchannel, and the further microchannels. The gas bubbles will block the fluidic flow. Solutions such as therapeutic agent may push and drive the bubbles move along the microchannels when a therapeutic agent reservoir may be under pressure or force. Shapes and cross-sectional size of microchannels may be designed to have various configurations such that gas bubbles inside the microchannels may be easily driven toward one direction only. Surface of microchannels may be designed to have different segments which may have either a hydrophobic surface or a hydrophilic surface. Due to the difference of surface tension between the microchannel segments of hydrophobic surface and hydrophilic surface, the gas bubbles inside the microchannels may be easily driven toward one direction only.

[0023] In an embodiment, the microfluidic arrangement may further include at least one cleansing agent reservoir configured to receive a cleansing agent. The cleansing agent may be used to clean the microscale pathways, rendering the microscale pathways relatively free of the micropore fluid before application of the therapeutic agent or to dilute the micropore fluid, depending on user requirements. The number of the cleansing agent reservoir(s) may depend on user and design requirements.

[0024] In an embodiment, the at least one cleansing agent reservoir may be in fluidic connection to the plurality of micropores via the at least one microchannel.

[0025] In an embodiment, the at least one cleansing agent reservoir may be positioned on one side of the plurality of micropores and the at least one therapeutic agent reservoir may be positioned on another side of the plurality of micropores.

[0026] In an embodiment, the microfluidic arrangement may further include at least one cleansing agent controller disposed between the at least one cleansing agent reservoir and at least one of the plurality of micropores, the at least one cleansing agent controller being configured so as to allow flow of the cleansing agent into at least one of the plurality of micropores upon application of a force upon the at least one cleansing agent reservoir.

[0027] Each cleansing agent controller may be positioned between each cleansing agent reservoir and each microchannel and/or between each microchannel and each micropore.

[0028] In an embodiment, the at least one cleansing agent controller may be a one-way valve which may allow flow of the cleansing agent in a single direction so as to prevent reflow of the cleansing agent or a breakable membrane.

[0029] In an embodiment, the microfluidic arrangement may further include at least one further microchannel fluidly connecting the at least one therapeutic agent reservoir with the at least one cleansing agent reservoir. The further microchannel may be included if the therapeutic agent is not in direct connection with the plurality of micropores.

[0030] In an embodiment, the microfluidic arrangement may further include at least one further therapeutic agent controller disposed between the at least one therapeutic agent reservoir and at least one of the plurality of micropores, the at least one further therapeutic controller being configured so as to allow flow of the therapeutic agent into at least one of the plurality of micropores upon application of a force upon the at least one therapeutic agent reservoir.

[0031] In an embodiment, the at least one further therapeutic agent controller may be a one-way valve which may allow flow of therapeutic agent in a single direction so as to prevent reflow of the therapeutic agent or a breakable membrane.

[0032] In an embodiment, the at least one cleansing agent reservoir may be positioned between the plurality of micropores and the at least one therapeutic agent reservoir. This may indicate that the at least one cleansing agent reservoir and the at least one therapeutic agent reservoir may be positioned on a same side of the plurality of micropores. The at least one cleansing agent reservoir and the at least one therapeutic agent reservoir may also be positioned on opposite sides of the plurality of micropores.

[0033] In an embodiment, the microfluidic arrangement may further include at least one further therapeutic agent reservoir configured to receive a further therapeutic agent.

[0034] In an embodiment, the microfluidic arrangement may further include at least one yet further microchannel fluidly connecting the at least one further therapeutic agent reservoir with the at least one therapeutic agent reservoir. [0035) In an embodiment, the microfluidic arrangement may further include at least one yet further therapeutic agent controller disposed between the at least one further therapeutic agent reservoir and at least one of the plurality of micropores, the at least one yet further therapeutic agent controller being configured so as to allow flow of the further therapeutic agent into at least one of the plurality of micropores upon application of a force upon the at least one further therapeutic agent reservoir.

[0036] In an embodiment, the at least one yet further therapeutic agent controller may be a one-way valve which may allow flow of the further therapeutic agent in a single direction so as to prevent reflow of the therapeutic agent or a breakable membrane.

[0037] In an embodiment, the passive drug delivery device further includes a support substrate arranged below the microfluidic arrangement, the support substrate may be configured to provide a support for the microfluidic arrangement. The support substrate may be made of a same or different material from the microfluidic arrangement. The support substrate may be made of a rigid material, thereby providing the support for the microfluidic arrangement.

[0038] In an embodiment, the microfluidic arrangement may be arranged on a single plane above the support substrate. The plurality of micropores, the at least one therapeutic agent reservoir, the at least one further therapeutic agent reservoir, the at least one cleansing agent reservoir, the at least one microchannel, the at least one further microchannel, the at least one yet further microchannel, the therapeutic agent controller, the further therapeutic agent controller and the cleansing agent controller may be arranged on a single plane or layer above the support substrate. |0039) In an embodiment, the microfluidic arrangement may be arranged in a stack layer arrangement above the support substrate. The plurality of micropores, the at least one therapeutic agent reservoir, the at least one further therapeutic agent reservoir, the at least one cleansing agent reservoir, the at least one microchannel, the at least one further microchannel, the at least one yet further microchannel, the therapeutic agent controller, the further therapeutic agent controller and the cleansing agent controller may be arranged on different planes or layers above the support substrate. Or some of the components may be on the same plane and others may be on different planes or layers above the support substrate.

[0040] By way of example, the at least one therapeutic agent reservoir, the at least one further therapeutic agent reservoir, the at least one cleansing agent reservoir may be arranged on a first layer above the support substrate. The at least one microchannel, the at least one further microchannel and the at least one yet further microchannel may be arranged on a second layer above the first layer. The plurality of micropores may be arranged on a third layer above the second layer. The respective plurality of micropores, the at least one therapeutic agent reservoir, the at least one further therapeutic agent reservoir, the at least one cleansing agent reservoir, the at least one microchannel, the at least one further microchannel, the at least one yet further microchannel, may be arranged on any suitable layers above the support substrate depending on user and design requirements.

[0041] In an embodiment, the microfluidic arrangement may further include an adhesive layer or a capping layer. The adhesive layer may be disposed over the third layer, wherein the adhesive layer may be removed prior to application on the skin. The adhesive layer may be a peel-off layer and configured to allow the microfluidic arrangement to be adhered onto the skin.

[0042] In an embodiment, the micropore fluid may be selected from the group consisting of Salicylic Acid, Citric Acid, Lactic Acid, and Glycolic Acid, any solutions which may etch and erosively damage the SC layer such that micrometer scales holes may be created through the SC layer.

[0043] In an embodiment, the therapeutic agent may be selected from the group consisting of certain pharmaceutically or medically effective excipients. These excipients may include softening agents (softeners), skin penetration enhancers or solubilizers in transdermal drug delivery systems. Exemplary materials include C₈ -C36 fatty acids such as isostearic acid, octanoic acid, and oleic acid; C8-C36 fatty alcohols such as oleyl alcohol and lauryl alcohol; lower alkyl esters of C₈-C36 fatty acids such as ethyl oleate, isopropyl myristate, butyl stearate, and methyl laurate; di(lower) alkyl esters of C6-C₈ diacids such as diisopropyl adipate; monoglycerides of C8-C36 fatty acids such as glyceryl monolaurate; tetraglycol (tetrahydrofurfuryl alcohol polyethylene glycol ether); tetraethylene glycol (ethanol,2,2'-(oxybis(ethylenoxy))diglycol); C6-C36 alkyl pyrrolidone carboxylates; polyethylene glycol; propylene glycol; 2-(2-ethoxyethoxy)ethanol; diethylene glycol monomethyl ether; N,N-dimethyldodecylamine-N-oxide and combinations of the foregoing. Alkylaryl ethers of polyethylene oxide, polyethylene oxide monomethyl ethers, and polyethylene oxide dimethyl ethers are also suitable, as are solubilizers such as glycerol and N-methyl pyrrolidone. The terpenes are another useful class of additives, including pinene, d-limonene, carene, terpineol, terpinen-4-ol, carveol, carvone, pulegone, piperitone, menthone, menthol, neomenthol, thymol, camphor, bomeol, citral, ionone, and cineole, alone or in any combination. Of the terpenes, terpineol, particularly .alpha.-terpineol, is preferred. Preferred excipients include glyceryl monolaurate, terpineol, lauryl alcohol, tetraglycol, tetraethylene glycol, propylene glycol, isopropyl myristate, ethyl oleate, methyl laurate, and 2-(2-ethoxyethoxy)ethanol.

[0044) In an embodiment, the further therapeutic agent may include any drug that may be suitable for transdermal delivery which may be used in the transdermal drug delivery composition of the invention. Examples of useful drugs include, but are not limited to, anti-inflammatory drugs, both steroidal (e.g., hydrocortisone, prednisolone, triamcinolone) and nonsteroidal (e.g., naproxen, piroxicam); antibacterials (e.g., penicillins such as penicillin V, cephalosporins such as cephalexin, erythromycin, tetracycline, gentamycin, sulfathiazole, nitrofurantoin, and quinolones such as norfloxacin, flumequine, and ibafloxacin); antiprotozoals (e.g., metronidazole); antifungals (e.g., nystatin); coronary vasodilators (e.g., nitroglycerin); calcium channel blockers (e.g., nifedipine, diltiazem); bronchodilators (e.g., theophylline, pirbuterol, salmeterol, isoproterenol); enzyme inhibitors such as collagenase inhibitors, protease inhibitors, elastase inhibitors, lipoxygenase inhibitors (e.g., zileuton), and angiotensin converting enzyme inhibitors (e.g., captopril, lisinopril); other antihypertensives (e.g., propranolol); leukotriene antagonists; anti-ulceratives such as H2 antagonists; steroidal hormones (e.g., progesterone, testosterone, estradiol); antivirals and/or immunomodulators (e.g., l-isobutyl-lH-iniidazo[4,5-c]qumolm-4-arriine, l-(2-hydroxy- 2-methylpropyl)-lH-imidazo[4,5-c]quinoline-4-amine, and other compounds disclosed in U.S. Pat. No. 4,689,338, incorporated herein by reference, acyclovir); local anesthetics (e.g., benzocaine, propofol); cardiotonics (e.g., digitalis, digoxin); antitussives (e.g., codeine, dextromethorphan); antihistamines (e.g., diphenhydramine, chlorpheniramine, terfenadine); narcotic analgesics (e.g., morphine, fentanyl); peptide hormones (e.g., human or animal growth hormones, LHRH); sex hormones (e.g., estrogens, testosterone, progestins such as levonorgestrel, norethindrone, gestodene); cardioactive products such as atriopep tides; proteinaceous products (e.g., insulin); enzymes (e.g., anti-plaque enzymes, lysozyme, dextranase); antinauseants (e.g., scopolomine); anticonvulsants (e.g., carbamazine); immunosuppressives (e.g., cyclosporine); psychotherapeutics (e.g., diazepam); sedatives (e.g., phenobarbital); anticoagulants (e.g., heparin); analgesics (e.g., acetaminophen); antimigraine agents (e.g., ergotamine, melatonin, sumatriptan); antiarrhythmic agents (e.g., flecainide); antiemetics (e.g., metaclopromide, ondansetron); anticancer agents (e.g., methotrexate); neurologic agents such as anxiolytic drugs; hemostatics; anti-obesity agents; and the like, as well as pharmaceutically acceptable salts and esters thereof. Preferred drugs include morphine and fentanyl.

|0045] In an embodiment, the further therapeutic agent may be the same or different from the therapeutic agent.

[0046] In an embodiment, the cleansing agent may be selected from the group consisting of saline and physiological buffer solution.

[0047] In an embodiment, the cleansing agent may be dimethyl sulfoxide (DMSO) first and further diluted in physiological buffer solution.

[0048] In an embodiment, the passive drug delivery device may be made of a flexible or an absorbent material. The flexible material may allow the passive drug delivery device to be adopted in any surface. This may render the passive drug delivery device wearable to the user. The flexible material may be a polymer-based material or any other suitable materials. The absorbent material may allow for absorption of the micropore fluid, the therapeutic agent, the further therapeutic agent or the cleansing agent upon activation of the respective reservoirs. The passive drug delivery device may be of any low cost material so as to provide a low cost solution to the user, for example rendering it suitable as a disposable alternative.

[0049] In an embodiment, the microfluidic arrangement may further include a first indicator disposed over the at least one therapeutic agent reservoir, wherein the first indicator may be adapted to provide an indication of the position of the at least one therapeutic agent reservoir and as to whether the at least one therapeutic agent reservoir has been activated.

(0050] In an embodiment, the microfluidic arrangement may further include a second indicator disposed over the at least one cleansing agent reservoir, wherein the second indicator may be adapted to provide an indication of the position of the at least one cleansing agent reservoir and as to whether the at least one cleansing agent reservoir has been activated.

[0051] In an embodiment, the microfluidic arrangement may further include a third indicator disposed over the at least one further therapeutic agent reservoir, wherein the third indicator may be adapted to provide an indication of the position of the at least one further therapeutic agent reservoir and as to whether the at least one further therapeutic agent reservoir has been activated.

[0052] In an embodiment, the first indicator may include a color indicator, texture indicator for example. The first indicator may be separately adhered onto the at least one therapeutic agent reservoir or may be a part of the at least one therapeutic agent reservoir. [0053] In an embodiment, the second indicator may include a color indicator, texture indicator, etc... The second indicator may be separately adhered onto the at least one cleansing agent reservoir or may be a part of the at least one cleansing agent reservoir.

[0054] In an embodiment, the third indicator may include a color indicator, texture indicator, for example. The third indicator may be separately adhered onto the at least one further therapeutic agent reservoir or may be a part of the at least one further therapeutic agent reservoir.

[0055] In an embodiment, the first indicator, the second indicator, the third indicator may be the same or different.

[0056] In an embodiment, the at least one therapeutic agent controller, the at least one cleansing agent controller, the at least one further therapeutic agent controller and the at least one yet further therapeutic agent controller may be the same or different.

[0057] In an embodiment, each micropore may be arranged at a predefined distance from each other. The distance between each micropore may be the same or different depending on user and design requirements. The distance between each micropore may be designed to maintain enough distance such that two created microscale pathways may not link together physically and form a larger microscale pathway.

[0058] Another embodiment relates to a method of passive drug delivery is provided. The method may include providing a micropore fluid capable of forming a microscale pathway in a stratum corneum layer of skin; and providing a therapeutic agent to the microscale pathway.

[0059] In an embodiment, the method may further include providing a cleansing agent to clean the microscale pathway. [0060] In an embodiment, the method may further include controlling flow of the therapeutic agent to the microscale pathway. The control of the therapeutic agent to the microscale pathway may be performed by a therapeutic agent controller.

[0061] In an embodiment, the method may further include controlling flow of the cleansing agent to the microscale pathway. The control of the cleansing agent to the microscale pathway may be performed by a cleansing agent controller.

[0062] In an embodiment, the method may further include providing a further therapeutic agent to the microscale pathway.

[0063] In an embodiment, the method may further include controlling flow of the further therapeutic agent to the microscale pathway. The control of the further therapeutic agent to the microscale pathway may be performed by a further therapeutic agent controller.

[0064] FIG. 1A and FIG. IB show respective top and cross-sectional side views of a passive drug delivery device 102 with one therapeutic agent reservoir 1 10 according to an embodiment. FIG. IB may be the side view as seen from the arrow as indicated in FIG. 1A.

[0065] The passive drug delivery device 102 includes a micro fluidic arrangement 104. The microfluidic arrangement 104 may include a plurality of micropores 106, each micropore 106 being configured to receive a micropore fluid 108 capable of forming a microscale pathway (not shown) in a stratum corneum layer of skin, wherein the plurality of micropores 106 may be arranged such that a plurality of microscale pathways may be formed by the micropore fluid 108 received in the plurality of micropores 106. Each micropore 106 may be arranged at a predefined distance from each other. The distance between each micropore 106 may be the same or different depending on user and design requirements.

[0066] The microfluidic arrangement 104 may also include a therapeutic agent reservoir 1 10 configured to receive a therapeutic agent 1 12 and four microchannels 1 14 connecting the plurality of micropores 106 with the therapeutic agent reservoir 1 10.

[0067] The microfluidic arrangement 104 may further include four therapeutic agent controllers 1 16, each therapeutic agent controller 1 16 disposed between the therapeutic agent reservoir 1 10 and at least one of the plurality of micropores 106, each therapeutic agent controller 1 16 being configured so as to allow flow of the therapeutic agent 1 12 into the at least one of the plurality of micropores 106 upon application of a force or pressure upon the therapeutic agent reservoir 1 10. The application of the force or pressure may be carried out by a user's hands or by other suitable means. Each therapeutic agent controller 1 16 may also be disposed between the therapeutic agent reservoir 110 and each microchannel 1 14 and/or between each microchannel 1 14 and each of the at least one of the plurality of micropores 106. Each therapeutic agent controller 1 16 may include a one-way valve which may allow flow of the therapeutic agent 1 12 in a single direction or a breakable membrane.

[0068] The passive drug delivery device 102 may further include a support substrate 1 18 arranged below the microfluidic arrangement 104, the support substrate 1 18 configured to provide a support for the microfluidic arrangement 104. The force or pressure may be applied indirectly upon the therapeutic agent reservoir 1 10 by pressing on a portion of the support substrate 1 18 corresponding to the position of the therapeutic agent reservoir 1 10. [0069] The micro fluidic arrangement 104 may be arranged in a stack layer arrangement above the support substrate 118. As shown in FIG. IB, the therapeutic agent reservoir 1 10 may be arranged on a first layer 120 above the support substrate 1 18. Each of the four microchannels 1 14 may be arranged on a second layer 122 above the first layer 120. The plurality of micropores 106 may be arranged on a third layer 124 above the second layer 122. The respective plurality of micropores 106, the microchannels 1 14 and the therapeutic agent reservoir 1 10 may be arranged on any suitable layers above the support substrate 1 18 depending on user and design requirements. Each therapeutic agent controller 1 16 may be arranged in a layer between the first layer 120 where the therapeutic agent reservoir 1 10 may be positioned and the second layer 122 where each microchannel 1 14 may be positioned. Each therapeutic agent controller 1 10 may also be arranged in a layer between the second layer 122 where each microchannel 1 14 may be positioned and the third layer 124 where the plurality of micropores 106 may be positioned.

[0070] The micropore fluid 108 may be selected from the group consisting of Salicylic Acid, Citric Acid, Lactic Acid, and Glycolic Acid, any solutions which may etch and erosively damage the SC layer such that micrometer scales holes may be created through the SC layer.

[0071] The passive drug delivery device 102 may be made of a flexible material so as to allow ease of application of any surface. The passive drug delivery device 102 may also be made of an absorbent material so as to be able to absorb the micropore fluid 108 or therapeutic agent 1 12 after respective activation. This may mean that the respective support substrate 118 and the first layer 120, the second layer 122 and the third layer 124 may be made of a flexible material and/or an absorbent material.

[0072] The operation of the passive drug delivery device 102 when in use may be described as follows. When in use, the user may provide a micropore fluid 108 capable of forming a microscale pathway in a stratum corneum layer of skin. This may be done by breaking the plurality of micropores 106, releasing the micropore fluid 108 onto the skin, thereby etching the skin and forming the microscale pathways. Then, the user may provide a therapeutic agent 1 12 to the microscale pathways and may also control the flow of the therapeutic agent 1 12 to the microscale pathways. This may be done by the application and controlling a force or pressure onto the therapeutic agent reservoir 1 10, thereby forcing the therapeutic agent 112 into the microchannels 114, the micropore 106 and finally onto the skin. The application of the force allows the opening of the therapeutic agent controller 1 16 and the intensity of the force allows the user to control the volume and flow of the therapeutic agent 1 12 onto the skin.

[0073] FIG. 2 A and FIG. 2B show respective top and cross-sectional side views of a passive drug delivery device 102 with one therapeutic agent reservoir 1 10 and one cleansing agent reservoir 126 arranged on opposite sides of a plurality of micropores 106 according to an embodiment. FIG. 2B may be the side view as seen from the arrow as indicated in FIG. 2 A.

(0074] Similar to FIG. 1A and FIG. IB, the passive drug delivery device 102 in FIG. 2A and FIG. 2B may include a micro fluidic arrangement 104 but with an additional cleansing agent reservoir 126 arranged on an opposite side of a plurality of micropores 106 from the therapeutic agent reservoir 110. [0075] The micro fluidic arrangement 104 may include a plurality of micropores 106, each micropore 106 being configured to receive a micropore fluid 108 capable of forming a microscale pathway in a stratum corneum layer of skin; wherein the plurality of micropores 106 may be arranged such that a plurality of microscale pathways may be formed by the micropore fluid 108 received in the plurality of micropores 106. Each micropore 106 may be arranged at a predefined distance from each other. The distance between each micropore 106 may be the same or different depending on user and design requirements.

[0076J The micro fluidic arrangement 104 may also include a therapeutic agent reservoir 1 10 configured to receive a therapeutic agent 1 12 and four microchannels 1 14 fluidly connecting the plurality of micropores 106 with the therapeutic agent reservoir 1 10.

[0077] The micro fluidic arrangement 104 may further include four therapeutic agent controllers 1 16, each therapeutic agent controller 1 16 disposed between the therapeutic agent reservoir 1 10 and at least one of the plurality of micropores 106, each therapeutic agent controller 116 being configured so as to allow flow of the therapeutic agent 1 12 into the at least one of the plurality of micropores 106 upon application of a force or pressure upon the therapeutic agent reservoir 1 10. The application of the force or pressure may be carried out by a user's hands or by other suitable means. For example, each therapeutic agent controller 1 16 may be disposed between the therapeutic agent reservoir 1 10 and each microchannel 1 14 (as shown in FIG. 2A and FIG. 2B) and/or between each microchannel 1 14 and each of the at least one of the plurality of micropores 106 (not shown). Each therapeutic agent controller 1 16 may include a one-way valve which may allow flow of the therapeutic agent 1 12 in a single direction or a breakable membrane.

[0078] The microfluidic arrangement 104 may further include a cleansing agent reservoir 126 configured to receive a cleansing agent 127. The cleansing agent reservoir 126 may be fluidly connected to the plurality of micropores 106 via the four microchannels 1 14.

[0079) The microfluidic arrangement 104 may further include four cleansing agent controllers 128, each cleansing agent controller 128 disposed between the cleansing agent reservoir 126 and the at least one of the plurality of micropores 106, each cleansing agent controller 128 being configured so as to allow flow of the cleansing agent 127 into the at least one of the plurality of micropores 106 upon application of a force or pressure upon the cleansing agent reservoir 126. Similar to the application of the force or pressure on the therapeutic agent reservoir 1 10, the application of the force may be carried out by the user's hands or by other suitable means. For example, each cleansing agent controller 128 may be disposed between the cleansing agent reservoir 126 and each microchannel 114 (as shown in FIG. 2A and FIG. 2B) and/or between each microchannel 1 14 and each of the at least one of the plurality of micropores 106 (not shown). Each cleansing agent controller 128 may be the same or different from the therapeutic agent controller 1 16 and may include a one-way valve which may allow flow of the cleansing agent 127 in a single direction or a breakable membrane.

[0080] The passive drug delivery device 102 may further include a support substrate 1 18 arranged below the microfluidic arrangement 104, the support substrate 1 18 configured to provide a support for the microfluidic arrangement 104. [0081] The microfluidic arrangement 104 may be arranged in a stack layer arrangement above the support substrate 1 18. As shown in FIG. 2B, the therapeutic agent reservoir 1 10 and the cleansing agent reservoir 126 may be arranged spaced apart on a first layer 120 above the support substrate 1 18. In an embodiment, the therapeutic agent reservoir 1 10 and the cleansing agent reservoir 126 may also be arranged on the first layer 120 adjacent to each other, in contact or a distance away from each other. Each of the four microchannels 1 14 may be arranged on a second layer 122 above the first layer 120. The plurality of micropores 106 may be arranged on a third layer 124 above the second layer 122. An adhesive layer 130 may be arranged on any suitable position above the third layer 124 wherein the adhesive layer 130 may be removed prior to application on the skin. The size of the adhesive layer 130 may vary depending on user and design requirements. The respective plurality of micropores 106, the therapeutic agent reservoir 1 10, the cleansing agent reservoir 126 and the microchannels 1 14 may be arranged on any suitable layers above the support substrate 1 18 depending on user and design requirements. Each therapeutic agent controller 1 16 may be arranged in a layer between the first layer 120 where the therapeutic agent reservoir 1 10 may be positioned and the second layer 122 where each microchannel 1 14 may be positioned as shown in FIG. 2B. Alternatively, each therapeutic agent controller 116 may also be arranged in a layer between the second layer 122 where each microchannel 1 14 may be positioned and the third layer 124 where the plurality of micropores 106 may be positioned but this may not be shown in FIG. 2B. Similarly, each cleansing agent controller 128 may be arranged in a layer between the first layer 120 where the cleansing agent reservoir 126 may be positioned and the second layer 122 where each microchannel 1 14 may be positioned as shown in FIG. 2B. Alternatively, each cleansing agent controller 128 may also be arranged in a layer between the second layer 122 where each microchannel 1 14 may be positioned and the third layer 124 where the plurality of micropores 106 may be positioned but this may not be shown in FIG. 2B.

[0082] In an embodiment, the support substrate 1 18 may be sized so as to be about the same length as the respective first layer 120, the second layer 122 and the third layer 124 or may be of a shorter or a longer length depending on design and user requirements.

[0083] The micropore fluid 106 may be selected from the group consisting of Salicylic Acid, Citric Acid, Lactic Acid, and Glycolic Acid, any solutions which may etch and erosively damage the SC layer such that micrometer scales holes may be created through the SC layer.

[0084] The therapeutic agent 1 12 may be selected from the list as mentioned above. The cleansing agent 127 may be selected from the group consisting of saline and physiological buffer solution.

[0085] The passive drug delivery device 102 may be made of a flexible material so as to allow ease of application of any surface. The passive drug delivery device 102 may also be made of an absorbent material so as to be able to absorb the micropore fluid 108, the therapeutic agent 112 or the cleansing agent 127 after respective activation.

[0086] The microfluidic arrangement 104 may further include a first indicator 132 disposed over the third layer 124 and above the position of the therapeutic agent reservoir 1 10, wherein the first indicator 132 may be adapted to provide an indication of the position of the therapeutic agent reservoir 1 10 and/or as to whether the therapeutic agent reservoir 1 10 has been activated. The first indicator 132 may also be positioned on the support substrate 1 18 depending on design and user requirements. The first indicator 132 may include a color indicator, texture indicator, for example. The first indicator 132 may be a separate layer adhered onto the third layer 124 or printed on the third layer 124. The size and the manner of incorporating the first indicator 132 may vary depending on user and design requirements.

[0087] The micro fluidic arrangement 104 may further include a second indicator 134 disposed over the third layer 124 and above the position of the cleansing agent reservoir 126, wherein the second indicator 134 may be adapted to provide an indication of the position of the cleansing agent reservoir 126 and as to whether the cleansing agent reservoir 126 has been activated. The second indicator 134 may also be positioned on the support substrate 1 18 depending on design and user requirements. The second indicator 134 may include a color indicator, texture indicator, for example. The first indicator 132 may be the same or different from the second indicator 134. The second indicator 134 may be a separate layer adhered onto the cleansing agent reservoir 126 or printed on the third layer 124. The size and the manner of incorporating the second indicator 134 may vary depending on user and design requirements.

[0088] The operation of the passive drug delivery device 102 when in use may be described as follows. When in use, the user may provide a micropore fluid 108 capable of forming a microscale pathway in a stratum corneum layer of skin. This may be done by breaking the plurality of micropores 106, releasing the micropore fluid 108 onto the skin, thereby etching the skin and forming the microscale pathways. The plurality of micropores 106 may be broken by an indirect force or pressure applied upon the respective therapeutic agent reservoir 110. [0089J Then the user may provide a cleansing agent 127 to clean the microscale pathways, rendering the microscale pathways relatively free of the micropore fluid 108. The user may also provide the cleansing agent 127 to dilute the micropore fluid 108, depending on user requirements. The user may also control the flow of the cleansing agent 127 to the microscale pathways. This may be done by the application and controlling of a force or pressure onto the cleansing agent reservoir 126, thereby forcing the cleansing agent 127 into the microchannels 1 14, the micropore 106 and finally onto the skin, washing away the micropore fluid 108. The application of the force allows the opening of the cleansing agent controller 128 and the intensity of the force allows the user to control the volume and flow of the cleansing agent 127 onto the skin.

[0090] Further, the user may provide a therapeutic agent 1 12 to the microscale pathway and control the flow of the therapeutic agent 1 12 to the microscale pathway. This may be done by the application and controlling of a force or pressure onto the therapeutic agent reservoir 1 10, thereby forcing the therapeutic agent 112 into the microchannels 1 14, the micropore 106 and finally onto the skin. The application of the force allows the opening of the therapeutic agent controller 1 16 and the intensity of the force allows the user to control the volume and flow of the therapeutic agent 112 onto the skin.

[0091] FIG. 3A and FIG. 3B show respective perspective and top views of a passive drug delivery device 102 with one therapeutic agent reservoir 110 and one cleansing agent reservoir 126 arranged on a same side of a plurality of micropores 106 according to an embodiment. FIG. 3C to FIG. 3E show respective cross-sectional side views of a passive drug delivery device 102 with one therapeutic agent reservoir 1 10 and one cleansing agent reservoir 126 arranged on a same side of a plurality of micropores 106 according to an embodiment.

[0092] Similar to FIG. 2A and FIG. 2B, the passive drug delivery device 102 in FIG. 3 A to FIG. 3E may include a microfluidic arrangement 104 but with the cleansing agent reservoir 126 arranged on a same side of the plurality of micropores 106 as the therapeutic agent reservoir 1 10. With this arrangement, an additional further microchannel 136 may be required to fluidly connect the therapeutic agent reservoir 1 10 to the cleansing agent reservoir 126.

[0093] The microfluidic arrangement 104 may include a plurality of micropores 106, each micropore 106 being configured to receive a micropore fluid 108 capable of forming a microscale pathway in a stratum corneum layer of skin; wherein the plurality of micropores 106 may be arranged such that a plurality of microscale pathways may be formed by the micropore fluid 108 received in the plurality of micropores 106. Each micropore 106 may be arranged at a predefined distance from each other. The distance between each micropore 106 may be the same or different depending on user and design requirements.

[0094] The microfluidic arrangement 104 may also include a cleansing agent reservoir 126 configured to receive a cleansing agent 127. The cleansing agent reservoir 126 may be fluidly connected to the plurality of micropores 106 via the five microchannels 1 14.

[0095] The microfluidic arrangement 104 may further include a therapeutic agent reservoir 1 10 configured to receive a therapeutic agent 1 12 and one further microchannel 136 fluidly connecting the therapeutic agent reservoir 1 10 with the cleansing agent reservoir 126. [0096] In FIG. 3 A to FIG. 3E, the cleansing agent reservoir 126 may be positioned between the plurality of micropores 106 and the therapeutic agent reservoir 1 10.

[0097J The micro fluidic arrangement 104 further includes five cleansing agent controllers 128, each cleansing agent controller 128 disposed between the cleansing agent reservoir 126 and the at least one of the plurality of micropores 106, each cleansing agent controller 128 being configured so as to allow flow of the cleansing agent 127 into the at least one of the plurality of micropores 106 upon application of a force or pressure upon the cleansing agent reservoir 126. The application of the force may be carried out by the user's hands or by other suitable means. Each cleansing agent controller 128 may be disposed between the cleansing agent reservoir 126 and each microchannel 1 14 and/or between each microchannel 1 14 and each of the at least one of the plurality of micropores 106. Each cleansing agent controller 128 may include a one-way valve which may allow flow of the cleansing agent 127 in a single direction or a breakable membrane.

[0098] The micro fluidic arrangement 104 may further include one further therapeutic agent controller 138 disposed between the therapeutic agent reservoir 1 10 and the further microchannel 136 or between the further microchannel 136 and the cleansing agent reservoir 126, the further therapeutic controller 138 being configured so as to allow flow of the therapeutic agent 1 12 into the further microchannel 136, then into the cleansing agent reservoir 126 before flowing into at least one of the plurality of micropores 106 upon application of a force upon the therapeutic agent reservoir 1 10.

10099] The further therapeutic agent controller 138 may be a one-way valve which allows flow of therapeutic agent 1 12 in a single direction or a breakable membrane. [00100] In an embodiment, the further therapeutic agent controller 138 may be the same or different from the cleansing agent controller 128.

[00101] In an embodiment, the amount of therapeutic agent 1 12 stored in the therapeutic agent reservoir 1 10 may be the same or slightly more than the amount of cleansing agent 127 stored in the cleansing agent reservoir 126. This may be to ensure delivery of a sufficient amount of therapeutic agent 1 12 to the microscale pathways in the skin, as some of the therapeutic agent 1 12 may remain in the therapeutic agent reservoir 1 10 if efforts are not taken to ensure that the entire amount of therapeutic agent 1 12 flows to the cleansing agent reservoir 126. The respective amount of therapeutic agent 1 12 housed in the therapeutic agent reservoir 1 10 and the cleansing agent 127 housed in the cleansing agent reservoir 126 may be more than the combined amount which may be housed in the microchannels 1 14 and the micropores 106 so as to ensure delivery of a sufficient amount of therapeutic agent 1 12 to the microscale pathways in the skin.

[00102] The passive drug delivery device 102 may further include a support substrate 1 18 arranged below the microfluidic arrangement 104, the support substrate 1 18 configured to provide a support for the microfluidic arrangement 104.

[00103] The microfluidic arrangement 104 may be arranged in a stack layer arrangement above the support substrate 118. As shown in FIG. 3C to FIG. 3E, the therapeutic agent reservoir 1 10, the cleansing agent reservoir 126 and the further microchannel 136 may be arranged adjacent to each other on a first layer 120 above the support substrate 118. Each of the five microchannels 1 14 may be arranged on a second layer 122 above the first layer 120. The plurality of micropores 106 may be arranged on a third layer 124 above the second layer 122. The respective plurality of micropores 106, the therapeutic agent reservoir 1 10, the cleansing agent reservoir 126, the five microchannels 1 14 and the further microchannel 136 may be arranged on any suitable layers above the support substrate 1 18 depending on user and design requirements.

[00104] Each cleansing agent controller 128 may be arranged in a layer between the first layer 120 where the cleansing agent reservoir 126 may be positioned and the second layer 122 where each microchannel 1 14 may be positioned. Each cleansing agent controller 128 may also be arranged in a layer between the second layer 122 where each microchannel 1 14 may be positioned and the third layer 124 where the plurality of micropores 106 may be positioned.

[00105] Each further therapeutic agent controller 1 16 may be arranged in the same layer as the layer where the therapeutic agent reservoir 1 10, the cleansing agent reservoir 126 and the further microchannel 136 may be positioned. Each further therapeutic agent controller 138 may also be arranged in a different layer from the layer where the therapeutic agent reservoir 1 10, the cleansing agent reservoir 126 and the further microchannel 136 may be positioned, depending on the desired dimensions of the micro fluidic arrangement 104 and the type of further therapeutic agent controller 138 used.

[00106] The micropore fluid 108 may be selected from the group consisting of Salicylic Acid, Citric Acid, Lactic Acid, and Glycolic Acid, any solutions which may etch and erosively damage the SC layer such that micrometer scales holes may be created through the SC layer. [00107] The therapeutic agent 1 12 may be selected from the list as mentioned above. The cleansing agent 127 may be selected from the group consisting of saline and physiological buffer solution.

[00108] The passive drug delivery device 102 may be made of a flexible material so as to allow ease of application of any surface. The passive drug delivery device 102 may also be made of an absorbent material so as to be able to absorb the micropore fluid 108, therapeutic agent 1 12 or cleansing agent 127 after respective activation.

[00109] The operation of the passive drug delivery device 102 when in use may be the same as in FIG. 2A and FIG. 2B and may be described as follows. When in use, the user may provide a micropore fluid 108 capable of forming a microscale pathway in a stratum corneum layer of skin. This may be done by breaking the plurality of micropore 106, releasing the micropore fluid 108 onto the skin, thereby etching the skin and forming the microscale pathways.

[00110] Then the user may provide a cleansing agent 127 to clean the microscale pathways, rendering the microscale pathways relatively free of the micropore fluid 108. The user may also provide the cleansing agent 127 to dilute the micropore fluid 108, depending on user requirements. The user may also control the flow of the cleansing agent 127 to the microscale pathways. This may be done by the application and controlling of a force or pressure onto the cleansing agent reservoir 126, thereby forcing the cleansing agent 127 into the microchannels 114, the micropore 106 and finally onto the skin, washing away the micropore fluid 108. The application of the force allows the opening of the cleansing agent controller 128 and the intensity of the force allows the user to control the volume and flow of the cleansing agent 127 onto the skin. [00111] Further, the user may provide a therapeutic agent 112 to the microscale pathway and control the flow of the therapeutic agent 1 12 to the microscale pathway. This may be done by the application and controlling of a force or pressure onto the therapeutic agent reservoir 1 10, thereby forcing the therapeutic agent 1 12 into the microchannels 1 14, the micropore 106 and finally onto the skin. The application of the force allows the opening of the further therapeutic agent controller 138 and the intensity of the force allows the user to control the volume and flow of the therapeutic agent 1 12 onto the skin.

[00112] The length of the passive drug delivery device 102 as shown in FIG. 3 A to FIG. 3E may be in the range of about 1 cm to 5 cm and the breadth may be in the range of about 0.5 cm to 2 cm. The length of the passive drug delivery device 102 as shown in FIG. 3 A to FIG. 3E may be slightly longer than the passive drug delivery device 102 as shown in FIG. 2A and FIG. 2B due to the additional further microchannel 136.

[00113] FIG. 4A and FIG. 4B show respective top and cross-sectional side views of a passive drug delivery device 102 with two different therapeutic agent reservoirs 1 10, 140 and one cleansing agent reservoir 126, the two different therapeutic agent reservoirs 1 10, 140 arranged on one side and the cleansing agent reservoir 126 arranged on another side of a plurality of micropores 106 according to an embodiment. FIG. 4B may be the side view as seen from the arrow as indicated in FIG. 4A.

[00114] Similar to FIG. 2A and FIG. 2B, the passive drug delivery device 102 in FIG. 4A to FIG. 4B may include a micro fluidic arrangement 104 with an additional further therapeutic agent reservoir 140 configured to receive a further therapeutic agent 141. [00115] The micro fluidic arrangement 104 may include a plurality of micropores 106, four microchannels 1 14, a cleansing agent reservoir 126, a therapeutic agent reservoir 110, a further therapeutic agent reservoir 140, four therapeutic agent controllers 1 16 and one cleansing agent controller 128. The two therapeutic agent reservoirs 1 10, 140 may be arranged on one side and the cleansing agent reservoir 126 arranged on another side of a plurality of micropores 106.

[00116] The therapeutic agent reservoir 1 10 may include the same or different therapeutic agent as the further therapeutic agent reservoir 140.

[00117] The micro fluidic arrangement 104 further includes a yet further microchannel 142 fluidly connecting the further therapeutic agent reservoir 140 with the therapeutic agent reservoir 1 10.

[00118] The microfluidic arrangement 104 further include a yet further therapeutic agent controller 144 disposed between the further therapeutic agent reservoir 140 and the yet further microchannel 142, the yet further therapeutic agent controller 144 being configured so as to allow flow of the further therapeutic agent 141 into the yet further microchannel 142 upon application of a force upon the yet further therapeutic agent reservoir 140. The yet further therapeutic agent controller 144 may also be disposed between the yet further microchannel 142 and the therapeutic agent reservoir 110. The position of the yet further therapeutic agent controller 144 may vary depending on user and design requirements. The yet further therapeutic agent controller 144 may be a oneway valve which allows flow of the further therapeutic agent 141 in a single direction or a breakable membrane. [00119] The passive drug delivery device 102 may further include a support substrate 1 18 arranged below the micro fluidic arrangement 104, the support substrate 1 18 configured to provide a support for the microfluidic arrangement 104.

[00120] The further therapeutic agent reservoir 140 may be positioned in the same first layer 120 as the therapeutic agent reservoir 1 10 and the cleansing agent reservoir 126. The yet further microchannel 142 may be positioned in the same second layer 122 as the four microchannels 1 14. The yet further therapeutic agent controller 144 may be disposed between the further therapeutic agent reservoir 140 and the yet further microchannel 142 or between the yet further microchannel 142 and the therapeutic agent reservoir 1 10.

[00121] FIG. 5A and FIG. 5B show respective perspective and top views of a passive drug delivery device 102 with two different therapeutic agent reservoirs 1 10, 140 and one cleansing agent reservoir 126 arranged on a same side of a plurality of micropores 106 according to an embodiment. FIG. 5B may be the side view as seen from the arrow as indicated in FIG. 5A.

[00122] Similar to FIG. 3 A to FIG. 3E, the passive drug delivery device 102 in FIG. 5 A to FIG. 5B may include a microfluidic arrangement 104 with a further therapeutic agent reservoir 140 configured to receive a further therapeutic agent 141.

[00123] The microfluidic arrangement 104 may include a plurality of micropores 106, four microchannels 1 14, a cleansing agent reservoir 126, a further microchannel 136, a therapeutic agent reservoir 1 10, a further therapeutic agent reservoir 140, four cleansing agent controllers 128 and a further therapeutic agent controller 138. The two therapeutic agent reservoirs 1 10, 140 and the cleansing agent reservoir 126 may be arranged on one side of a plurality of micropores 106.

[00124] The therapeutic agent reservoir 1 10 may include the same or different therapeutic agent as the further therapeutic agent reservoir 140.

[00125) The microfluidic arrangement 104 further includes a yet further microchannel 142 fluidly connecting the further therapeutic agent reservoir 140 with the therapeutic agent reservoir 1 10.

[00126] The microfluidic arrangement 104 further include one yet further therapeutic agent controller 144 disposed between the further therapeutic agent reservoir 140 and the yet further microchannel 142, the yet further therapeutic agent controller 144 being configured so as to allow flow of the further therapeutic agent 141 into the yet further microchannel 142 upon application of a force upon the yet further therapeutic agent reservoir 144. The yet further therapeutic agent controller 144 may also be disposed between the yet further microchannel 142 and the therapeutic agent reservoir 1 10. The position of the yet further therapeutic agent controller 144 may vary depending on user and design requirements. The yet further therapeutic agent controller 144 may be a oneway valve which allows flow of the further therapeutic agent 141 in a single direction or a breakable membrane.

[00127] The further therapeutic agent reservoir 140 may be positioned in the same first layer 120 as the therapeutic agent reservoir 1 10 and the cleansing agent reservoir 126. The yet further microchannel 142 may be positioned in the same second layer 122 as the four microchannels 114 and the further microchannel 136. The yet further therapeutic agent controller 144 may be disposed between the further therapeutic agent reservoir 140 and the yet further microchannel 142 or between the yet further microchannel 142 and the therapeutic agent reservoir 1 10.

[00128] FIG. 6A and FIG. 6B show respective top and cross-sectional side views of a passive drug delivery device 102 with four similar therapeutic agent reservoirs 1 10 and four similar cleansing agent reservoirs 126, the four similar therapeutic agent reservoirs 1 10 arranged on one side and the four similar cleansing agent reservoirs 126 arranged on another side of a plurality of micropores 106 according to an embodiment.

[00129] FIG. 6A and FIG. 6B is similar to FIG. 2A and FIG. 2B except that the passive drug delivery device 102 in FIG. 6A and FIG. 6B may include a plurality of micro fluidic arrangements 104 on the support substrate 1 18 compared to only one microfluidic arrangement 104 in FIG. 2A and FIG. 2B. FIG. 6B may be the side view as seen from the arrow as indicated in FIG. 6A.

[00130] The microfluidic arrangement 104 may include a plurality of micropores 106, four microchannels 1 14, four cleansing agent reservoirs 126, four therapeutic agent reservoirs 1 10, four therapeutic agent controllers 116 and four cleansing agent controllers 128. The four therapeutic agent reservoirs 1 10 may be arranged on one side and the four cleansing agent reservoirs 126 arranged on another side of a plurality of micropores 106.

[00131] Each of the four therapeutic agent reservoirs 1 10 may include the same therapeutic agent and each of the four cleansing agent reservoirs 126 may include the same cleansing agent.

[00132] FIG. 7A and FIG. 7B show respective top and cross-sectional side views of a passive drug delivery device 102 with four different therapeutic agent reservoirs 1 10 and four similar cleansing agent reservoirs 126 arranged on the support substrate 1 18. The four different therapeutic agent reservoirs 1 10 arranged on one side and the four similar cleansing agent reservoirs 126 arranged on another side of a plurality of micropores 106 according to an embodiment. FIG. 7B may be the side view as seen from the arrow as indicated in FIG. 7A.

[00133J FIG. 7A and FIG. 7B is similar to FIG. 6A and FIG. 6B except that the passive drug delivery device 102 in FIG. 7A and FIG. 7B may include four therapeutic agent reservoirs 1 10 with different therapeutic agents 1 12 compared to four therapeutic agent reservoirs 110 with the same therapeutic agent 1 12 as shown in FIG. 6A and FIG. 6B.

[00134] The micro fluidic arrangement 104 may include a plurality of micropores 106, four microchannels 1 14, four cleansing agent reservoirs 126, four therapeutic agent reservoirs 1 10, four therapeutic agent controllers 1 16 and four cleansing agent controllers 128. The four therapeutic agent reservoirs 1 10 may be arranged on one side and the four cleansing agent reservoirs 126 arranged on another side of a plurality of micropores 106.

[00135] Each of the four therapeutic agent reservoirs 1 10 may include a different therapeutic agent 112 and each of the four cleansing agent reservoirs 126 may include the same cleansing agent 127. However, each of the four cleansing agent reservoirs 126 may also include a different cleansing agent 127 depending on user and design requirements.

[00136] FIG. 8A shows a cross-sectional side view of a passive drug delivery device 102 with one therapeutic agent reservoir 1 10 and one cleansing agent reservoir 126 arranged on opposite sides of a plurality of micropores 106 with an adhesive layer 130 positioned around the plurality of micropores 106 and the respective therapeutic agent reservoir 1 10 and the cleansing agent reservoir 126 and the adhesive layer 130 further positioned between each of the plurality of micropores 106 according to an embodiment

[00137] FIG. 8A may be similar to FIG. 2B with the adhesive layer 130 further positioned between each of the plurality of micropores 106. Each of the plurality of micropores 106 may be surrounded by a portion of the adhesive layer 130 such that the micropore fluid 108 contained within each of the plurality of micropores 106 may be confined within the micropore 106. The additional surface area of the adhesive layer 130 may facilitate the adhesion of the passive drug delivery device 102 onto the skin surface.

[00138] FIG. 8B shows a cross-sectional side view of a passive drug delivery device 102 with one therapeutic agent reservoir 1 10 and one cleansing agent reservoir 126 arranged on opposite sides of a plurality of micropores 106 with an adhesive layer 130 positioned around the plurality of micropores 106 and the respective therapeutic agent reservoir 1 10 and the cleansing agent reservoir 126, the adhesive layer 130 further positioned between each of the plurality of micropores 106 and with a cover layer 146 positioned over the plurality of micropores 106, the first indicator 132, the second indicator 134 and the adhesive layer 130 according to an embodiment.

[00139] FIG. 8B may be similar to FIG. 8A with an additional cover layer or shielding layer 146 positioned at least over the plurality of micropores 106, the first indicator 132, the second indicator 134 and the adhesive layer 130 or over the micro fluidic arrangement 104 such that a surface of the micropore 106 may be sealed so that the micropore fluid 108 may be kept inside the micropore 106. When an user remove the cover layer 146 from the micro fluidic arrangement 104, the passive drug delivery device 102 may be that as shown in FIG. 8 A. The cover layer 146 may be made of any suitable material configured to prevent the leakage of the micropore fluid 108.

[00140] While the invention has been particularly shown and described with reference to specific embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. The scope of the invention is thus indicated by the appended claims and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced.

Claims

Claims What is claimed is:

1. A passive drug delivery device comprising a microfluidic arrangement,

the microfluidic arrangement comprising :

a plurality of micropores, each micropore being configured to receive a micropore fluid capable of forming a microscale pathway in a stratum corneum layer of skin; wherein the plurality of micropores are arranged such that a plurality of microscale pathways can be formed by the micropore fluid received in the plurality of micropores;

at least one therapeutic agent reservoir configured to receive a therapeutic agent; and

at least one microchannel connecting the plurality of micropores with the at least one therapeutic agent reservoir.

2. The passive drug delivery device of claim 1 ,

wherein the microfluidic arrangement further comprises at least one therapeutic agent controller disposed between the at least one therapeutic agent reservoir and at least one of the plurality of micropores, the at least one therapeutic agent controller being configured so as to allow flow of the therapeutic agent into at least one of the plurality of micropores upon application of a force upon the at least one therapeutic agent reservoir.

3. The passive drug delivery device of claim 2, wherein the at least one therapeutic agent controller comprises a one-way valve which allows flow of the therapeutic agent in a single direction.

4. The passive drug delivery device of any one of claims 1 to 3,

wherein the microfluidic arrangement further comprises at least one cleansing agent reservoir configured to receive a cleansing agent.

5. The passive drug delivery device of claim 4,

wherein the at least one cleansing agent reservoir is fluidly connected to the plurality of micropores via the at least one microchannel.

6. The passive drug delivery device of claim 4 or 5,

wherein the microfluidic arrangement further comprises at least one cleansing agent controller disposed between the at least one cleansing agent reservoir and at least one of the plurality of micropores, the at least one cleansing agent controller being configured so as to allow flow of the cleansing agent into at least one of the plurality of micropores upon application of a force upon the at least one cleansing agent reservoir.

7. The passive drug delivery device of claim 6,

wherein the at least one cleansing agent controller is a one-way valve which allows flow of the cleansing agent in a single direction.

8. The passive drug delivery device of any one of claims 4 to 7, wherein the microfluidic arrangement further comprises at least one further microchannel fluidly connecting the at least one therapeutic agent reservoir with the at least one cleansing agent reservoir.

9. The passive drug delivery device of claim 8,

wherein the microfluidic arrangement further comprises at least one further therapeutic agent controller disposed between the at least one therapeutic agent reservoir and at least one of the plurality of micropores, the at least one further therapeutic controller being configured so as to allow flow of the therapeutic agent into at least one of the plurality of micropores upon application of a force upon the at least one therapeutic agent reservoir.

10. The passive drug delivery device of claim 9,

wherein the at least one further therapeutic agent controller is a one-way valve which allows flow of therapeutic agent in a single direction.

1 1. The passive drug delivery device of any one of claims 4 to 10,

wherein the at least one cleansing agent reservoir is positioned between the plurality of micropores and the at least one therapeutic agent reservoir.

12. The passive drug delivery device of any one of claims 1 to 1 1 , wherein the microfluidic arrangement further comprises at least one further therapeutic agent reservoir configured to receive a further therapeutic agent.

13. The passive drug delivery device of claim 12,

wherein the microfluidic arrangement further comprises at least one yet further microchannel fluidly connecting the at least one further therapeutic agent reservoir with the at least one therapeutic agent reservoir.

14. The passive drug delivery device of claim 13,

wherein the microfluidic arrangement further comprises at least one yet further therapeutic agent controller disposed between the at least one further therapeutic agent reservoir and at least one of the plurality of micropores, the at least one yet further therapeutic agent controller being configured so as to allow flow of the further therapeutic agent into at least one of the plurality of micropores upon application of a force upon the at least one further therapeutic agent reservoir.

15. The passive drug delivery device of claim 14,

wherein the at least one yet further therapeutic agent controller is a one-way valve which allows flow of the further therapeutic agent in a single direction.

16. The passive drug delivery device of any one of claims 1 to 15,

wherein the microfluidic arrangement further comprises an adhesive layer.

17. The passive drug delivery device of any one of claims 1 to 16, further comprising: a support substrate arranged below the microfluidic arrangement, the support substrate configured to provide a support for the microfluidic arrangement.

18. The passive drug delivery device of claim 17,

wherein the microfluidic arrangement is arranged on a single plane above the support substrate.

19. A method of drug delivery, the method comprising:

providing a micropore fluid capable of forming a microscale pathway in a stratum corneum layer of skin; and

providing a therapeutic agent to the microscale pathway.

20. The method of claim 19, further comprising:

providing a cleansing agent to clean the microscale pathway.