CN215387005U - Medicine-containing micro-needle patch with exposed needle tip - Google Patents

Abstract

The utility model provides a drug-containing microneedle patch with an exposed needle tip, which at least comprises a substrate; at least one microneedle extending downward from the bottom of the base body, the two microneedles are connected together to form a microneedle patch, wherein the tip of the microneedle is tapered; and a transdermal drug delivery device covering the outer periphery of the body of the microneedle to form a drug-containing microneedle patch and exposing the needle tip. The utility model has the advantage of greatly improving the success rate of puncture.

Description

Medicine-containing micro-needle patch with exposed needle tip

Technical Field

The present invention relates to the field of medical devices.

Background

It is also known that Transdermal Drug Delivery Systems (TDDS) are an emerging route of administration, and in 1998, Mark Prausnitz uses silicon to make microneedle patches (MNP) and stains with Calcein AM (Calcein AM) to confirm that microneedle patches are useful for drug delivery. The microneedle patch can be used as a drug carrier, has wide application range, and comprises daily drug delivery and beauty maintenance, wherein the microneedle patch can be divided into the following components according to different drug delivery modes: solid microneedles, coating microneedles, hollow microneedles, soluble microneedles and the like, wherein the solid microneedles are coated with drugs after a microchannel is manufactured on a horny layer, so that the drugs can enter the skin through the microchannel; the coating type microneedle is used for coating a drug on the surface of the microneedle, and the drug can be diffused in the skin after the microneedle punctures the stratum corneum; the hollow micro-needle is similar to the traditional injection, and the medicine can be contained in the micro-needle and pushed into the skin to be diffused in an injection mode; the dissolvable microneedle is prepared from water-soluble or biodegradable materials, and the drug is placed in the microneedle, and the microneedle structure dissolves after puncturing the skin, so that the drug can be released and diffused. Chitosan microneedles are highly biocompatible, in addition to the microneedle types described above.

In the meantime, the microneedle patch can also be used for vaccine delivery, and clinically common vaccination modes include oral administration, subcutaneous administration and intramuscular injection, wherein the oral administration vaccines include rotavirus vaccines, the subcutaneous injection vaccines include japanese encephalitis vaccines and varicella vaccines, and the intramuscular injection vaccines include influenza vaccines and hepatitis B vaccines. The ideal vaccine refers to a vaccine type (such as oral vaccine) which is easy to inoculate, and the microneedle patch has the advantages of reducing pain and discomfort, reducing the risk of injection infection due to small inoculation wound and the like, and is expected to become the ideal vaccine type after the oral vaccine.

According to the aspect of the micro needles, the micro needles can be bullet type, pyramid type, cone type and spike type, the structure is a micron (mum) grade structure, the length is about 200 to 2000 microns, the diameter can reach 1 micron at the minimum, each micro needle can puncture the horny layer under the condition of the minimum mechanical strength of 0.058N and can deliver the medicine to the epidermis layer and the dermis layer (namely, transdermal medicine delivery), and the micro needles are short and short enough to stimulate the nerve end, so that the pain can be avoided.

Generally, the micro-needle containing medicine (i.e. the micro-needle patch is already provided with medicine) is mostly made of water-containing polymer capable of bearing medicine, the composition of the polymer is soft material and is prepared by casting PDMS flexible mould, because the polymer contains water, the mechanical property is not good, the elastic modulus is usually less than 10 MPa (megapascal), the yield strength is usually less than 100 MPa, thus, the mechanical strength of the micro-needle containing medicine is limited for skin penetration, the needle point is often bent and can not penetrate into the skin in application, so that the micro-needle containing medicine can not be applied to subcutaneous injection administration requiring precise dosage, therefore, the micro-needle containing medicine is still limited in the application of beauty, skin care and the like which do not require dosage control.

Therefore, how to increase the rigidity of the medicated microneedle and avoid the needle tip being easy to bend and unable to pierce the epidermis is a target of many enterprise researches, and the currently known ways include: the first is to use chemical cross-linking agent, although it can obviously improve the strength of the micro-needle containing medicine, but will introduce the cross-linking component with biological toxicity; the second method is to use physical cross-linking (e.g. freezing and thawing the microneedles several times), which can increase the strength of the microneedles several times, but the strength is still insufficient compared to the strength required for successful skin puncture, and the repeated freezing and thawing process is not suitable for mass production of microneedles.

The third is to combine the micro-needle containing medicine with the hard non-water macromolecule support seat. Generally, in order to prevent the needle tip of the conventional drug-containing microneedle from deforming, the common ratio of the height of the needle body to the base of the microneedle is 1: 1, not more than 3 at most: 1, therefore, in practice, the needle body of the drug-containing microneedle can penetrate into the skin to a depth of 300 μm or less, and can not reach the penetration depth (1000 μm) of the pain nerve. Although the third method adds a hard support structure to the outer periphery of the soft needle tip to effectively push the medicine to a position closer to the vascular plexus, the puncturing action of the above structure still depends on the soft needle tip, and the needle tip is still subject to the possibility of being bent and unable to puncture successfully. Therefore, how to effectively solve the aforementioned problems to provide a microneedle product with better quality is an important subject of the present invention.

Disclosure of Invention

Since the mechanical strength of the conventional microneedle patch containing drug still needs to be enhanced, after repeated research and test, the inventor finally developed a microneedle patch containing drug with exposed needle tips, which can effectively solve the conventional problems by means of the utility model. The technical scheme of the utility model is as follows:

at least comprises the following steps:

a substrate;

at least one microneedle extending downward from the bottom of the base body, the two microneedles are connected together to form a microneedle patch, wherein the tip of the microneedle is tapered; and

a transdermal drug delivery, which is coated on the outer periphery of the body of the micro-needle to form a micro-needle patch containing the drug and can expose the needle point.

The longitudinal length from the top side to the bottom side of the microneedle forms a microneedle height, the transverse length of the top side of the microneedle forms a microneedle width, and the ratio of the microneedle height to the microneedle width is 1: 1 to 12: 1.

the longitudinal height ratio of the microneedle tip to the microneedle body is 1: 4 to 1: 10.

the microneedle has an elastic modulus value of 1 GPa to 7 GPa.

The microneedle patch is characterized in that microneedles can be inserted into a cavity which is formed by downwards concave on the top surface of a mould, the cavity is filled with a medicament delivered through skin, the microneedle body is adhered with the medicament delivered through skin in the cavity and can be withdrawn from the cavity, and the downwards concave cavity is conical and is provided with an upper cavity part and a lower cavity part or is only provided with a single cavity.

The top surface of the mould is downwards concavely provided with a single cavity, the micro-needle of the micro-needle patch is inserted into the cavity, and the needle point of the micro-needle pierces the bottom layer of the cavity.

The inner bottom surface of the single cavity of the mold is made of silica gel.

The upper chamber part of the mould cavity is used for accommodating a microneedle body of a microneedle patch, the lower chamber part of the mould cavity is used for accommodating a microneedle needlepoint of the microneedle patch, and the upper chamber part of the cavity is filled with a medicament which is delivered through skin and cannot enter the lower chamber part of the cavity.

The clearance between the outer surface of the needle tip and the inner surface of the lower chamber part is smaller than the particle size of the medicament to be delivered through the skin.

The utility model has the advantage of greatly improving the success rate of puncture.

Drawings

FIG. 1 is a perspective view of a microneedle patch containing a drug according to the present invention;

FIG. 2 is a schematic partial cross-sectional view of a microneedle patch containing a drug in accordance with the present invention;

FIG. 3A is a schematic partial cross-sectional view of a mold for a microneedle patch containing a drug in accordance with the present invention;

FIG. 3B is a schematic cross-sectional view of a transdermal drug delivery mold for a microneedle patch containing a drug of the present invention;

FIG. 3C is a schematic partial cross-sectional view of a microneedle patch of the present invention incorporating a drug-containing microneedle patch extending into a mold;

FIG. 3D is a schematic cross-sectional view of a microneedle patch incorporating a drug-containing microneedle patch of the present invention in combination with a transdermal drug delivery device in a mold;

FIG. 3E is a schematic cross-sectional view of a microneedle patch incorporating a drug-containing microneedle patch of the present invention in combination with transdermal drug delivery;

FIG. 3F is a schematic perspective view of a microneedle patch of the present invention;

FIG. 4 is a flow chart of the fabrication of a drug-containing microneedle patch of the present invention;

FIG. 5A is a schematic partial cross-sectional view of a microneedle patch extending into a mold in accordance with another method for making a microneedle patch containing a drug of the present invention;

FIG. 5B is a schematic cross-sectional view of another microneedle patch of the present invention in combination with a mold;

FIG. 5C is a schematic cross-sectional view of another transdermal drug delivery mold of the present invention containing microneedle patch;

FIG. 5D is a schematic cross-sectional view of another drug-containing microneedle patch of the present invention in combination with transdermal drug delivery;

fig. 6 is a flow chart of another method for manufacturing a microneedle patch containing drug.

The main reference symbols in the drawings illustrate that:

1: microneedle patch containing medicine

11: base body

13: microneedle

131: needle body

133: needle tip

15: transdermal drug delivery

2. 4: die set

20. 40: chamber

401: upper chamber part

402: lower chamber part

H: height of microneedle

W: the width of the microneedles.

Detailed Description

In order to make the objects, technical contents and advantages of the present invention more apparent, the embodiments of the present invention disclosed in the following are further described in detail with reference to the accompanying drawings in combination with the detailed description.

A base body 11;

at least one microneedle 13 extending downward from the bottom surface of the base 11, and the two microneedles are connected together to form a microneedle patch, wherein the tip of the microneedle 13 is cone-shaped; and

a transdermal drug delivery 15, which covers the outer periphery of the body of the microneedle 13 to form a drug-containing microneedle patch 1, and the needle tip can be exposed.

The longitudinal length from the top side to the bottom side of the microneedle 13 forms a microneedle height H, the axial length of the top side of the microneedle 13 forms a microneedle width w, and the ratio of the microneedle height to the microneedle width is 1: 1 to 12: 1.

the longitudinal height ratio of the microneedle tip to the microneedle body is 1: 4 to 1: 10.

the microneedle has an elastic modulus value of 1 GPa to 7 GPa.

The microneedle patch 1 is characterized in that microneedles 13 can be inserted into cavities 20 and 40 which are formed by downwards concave top surfaces of molds 2 and 4, the cavities are filled with transdermal delivery drugs, the microneedles can be withdrawn from the cavities 20 and 40, a body 11 of the withdrawn microneedles 13 is coated with the transdermal delivery drugs 15 to form the microneedle patch 1 containing the microneedles, and the downwards concave cavities 20 and 40 are conical and are provided with an upper cavity part 401 and a lower cavity part 402 or are only provided with a single cavity 20.

The top surface of the mold 2 is provided with a single cavity 20 which is concave downwards, the micro-needle 13 of the micro-needle patch 1 is inserted into the cavity 20, and the needle point 133 of the micro-needle 13 pierces the bottom layer of the cavity.

The inner bottom surface of the single cavity 20 of the mold 2 is made of silica gel.

The upper chamber part 401 of the cavity 40 of the mold 4 accommodates the microneedle body 131 of the microneedle patch 1, the lower chamber part 402 of the cavity of the mold 4 accommodates the microneedle 133 of the microneedle patch, the upper chamber part 401 of the cavity is filled with the drug 15 to be delivered through the skin, and the drug 15 cannot enter the lower chamber part 401 of the cavity.

The clearance between the outer surface of the needle tip 133 and the inner surface of the lower chamber portion 402 is smaller than the particle size of the drug 15 to be delivered transdermally.

Those skilled in the art can appreciate advantages and benefits from the present disclosure and that they may be practiced or carried out in other embodiments, variations and modifications of the present disclosure, which may be within the spirit and scope of the present disclosure, may be learned by practice of the disclosure, and it is to be understood that various other changes may be made and equivalents will be resorted to, falling within the scope of the disclosure, the drawings being set forth hereinafter for the purpose of illustration and description.

It should be understood that the examples used anywhere in the specification of the utility model, including the use of any term, are illustrative only and are not intended to limit the scope or meaning of the utility model or any term. Likewise, the utility model is not limited to the various embodiments disclosed in the specification. Although the terms first, second, third, etc. may be used herein to describe various elements, these elements should not be limited by the foregoing terms, which are primarily used to distinguish one element from another, should not impose any substantial limitations on any elements, and should not restrict the order in which the elements are assembled or arranged in actual use. Further, directional phrases used in connection with the embodiments, such as "upper," "lower," "left," "right," etc., are used solely in reference to the orientation of the drawings. Accordingly, the directional terminology used is intended to be in the nature of words of description rather than of limitation.

In one embodiment, referring to fig. 1 and 2, the microneedle patch 1 includes a substrate 11, at least one microneedle 13, and a transdermal drug delivery device 15, for convenience of describing the relative relationship between the components, the upper part of fig. 2 is used as the upper (top) position of the component, the lower part of fig. 2 is used as the lower (bottom) position of the component, the left part of fig. 2 is used as the left position of the component, and the right part of fig. 2 is used as the right position of the component. In addition, the mode of the microneedle patch 1 containing drug of the present invention is not limited to the mode drawn in fig. 1, and the manufacturer can adjust the mode of each component according to the product requirement, so as long as the microneedle patch 1 containing drug has the related basic structure and function of the following embodiments, it is the microneedle patch 1 containing drug to be protected in the present invention, and it is well known in advance.

Referring to fig. 1 and 2 again, the substrate 11 can be a flat plate, and the bottom surface thereof can extend downward to form the microneedles 13, wherein the microneedles 13 can be solid and include a needle body 131 and a needle point 133 from top to bottom, and at least the needle point 133 can be tapered to effectively pierce the skin of the human body. The transdermal drug delivery system 15 may include an Active Pharmaceutical Ingredients (API) and hyaluronic acid, chitin, collagen or gelatin … compatible with the Active Pharmaceutical Ingredients, and only covers the outer surface of the body 131 of the microneedle 13 and exposes the needle point 133 to form a drug-containing microneedle. That is, the appearance of the microneedle containing drug of the present invention can form two parts, the first is the "soft drug-containing layer" corresponding to the needle body 131 and the drug 15 to be delivered through skin on the outer edge of the needle body, and the second is the "hard piercing part" corresponding to the needle point 133, so that when the microneedle patch 1 containing drug is used by a user, the needle point 133 can pierce the stratum corneum of the skin of the human body, and then the drug 15 to be delivered through skin enters the skin along with the needle body 131, and further the drug 15 to be delivered through skin can be released and diffused. In addition, in the embodiment, the substrate 11 and the microneedles 13 can be integrally formed, but not limited thereto, in other embodiments of the utility model, the substrate 11 and the microneedles 13 can be manufactured into separate components and then integrated into a whole according to different requirements and processes of the product.

In view of fig. 1 and 2, in order to make the microneedles 13 effectively pierce the stratum corneum of the skin and not lose their effectiveness (i.e., cannot pierce the skin) due to bending when piercing the stratum corneum of the skin, the microneedles 13 have the following two structural features after the research and experiment of the inventor:

(1) the ratio of the longitudinal height of the needle tip 133 to the needle body 131 can be 1: 4 to 1: 10, so as to ensure that the exposed length of the needle tip 133 (i.e., the "hard piercing portion") protrudes far beyond the drug 15 for transdermal delivery (i.e., the "soft drug-containing layer") sufficiently to preferentially contact and penetrate the stratum corneum of the skin, and then to concomitantly cause the drug 15 for transdermal delivery to enter the skin;

(2) the ideal elastic modulus value of the microneedle 13 is 1 GPa (gigapascal) to 7GPa, and the ratio of the height H of the microneedle to the width W of the microneedle can be 1: 1 to 12: 1, the microneedle height H refers to the longitudinal length from the top side to the bottom side of the microneedle 13, and the microneedle width W refers to the lateral length of the top side of the microneedle 13, so that the microneedle 13 does not bend and fail when piercing the stratum corneum of the skin. Furthermore, if it is desired to have the smallest microneedle 13 capable of carrying the largest amount of drug, it is more preferable to make the microneedle 13 from a material with a thickness larger than 3GPa, such as Polyetheretherketone (PEEK) or Polymethylmethacrylate (PMMA), wherein PEEK is a biocompatible high temperature resistant engineering plastic, PMMA can be used as the raw material of the dental prosthesis and bone cement, but not limited thereto, and in other embodiments of the present invention, the microneedle 13 can also be made of Polycarbonate (PC), polylactic acid (PLA), Acrylonitrile Butadiene Styrene (ABS), polypropylene (PP), silicone, epoxy resin or other thermoplastic or thermosetting polymer materials with certain biocompatibility found in medical devices.

Referring to fig. 1 and 2 again, in order to effectively manufacture the aforesaid microneedle patch 1, especially, to ensure that the needle point 133 can be exposed and the transdermal drug delivery 15 can completely cover the needle body 131, the present invention develops two manufacturing methods, which are described in detail later, in the first manufacturing method of the present invention, referring to fig. 3A to 3B and 4, firstly, a filling operation is performed to fill the transdermal drug delivery 15 into at least one cavity 20 of a mold 2, wherein the top surface of the mold 2 can be recessed with each cavity 20 (as shown in fig. 3A), the cavity 20 can be tapered (but not limited thereto), and the liquid transdermal drug delivery 15 can be injected into the cavity 20 (as shown in fig. 3B); thereafter, a coagulation period can be waited for to make the drug 15 in semi-hardened state, wherein the practitioner can adjust the length of the coagulation period according to the actual requirement and the material property of the drug 15, even without waiting for the coagulation period.

As shown in fig. 3C to 3F and fig. 4, an inserting operation is performed to move the bottom surface of the substrate 11 toward the top surface of the mold 2, so that each microneedle 13 can extend into the corresponding cavity 20 (as shown in fig. 3C), so that only a single microneedle 13 is accommodated in each cavity 20 until the needlepoint 133 of the microneedle 13 pierces the inner bottom surface of the corresponding cavity 20, and the body 131 of the microneedle 13 can be located in the cavity 20 but does not touch the inner wall surface of the cavity 20 (as shown in fig. 3D), so as to be covered by the transdermally delivered drug 15; also waiting for a set period until the transdermally delivered agent 15 hardens and becomes secured to the needle body 131; finally, a demolding operation is performed to separate both the transdermal drug delivery 15 and the microneedles 13 from the inner wall surface of the cavity 20 (as shown in fig. 3E), so as to expose the needle tips 133, thereby forming the drug-containing microneedle patch 1 (as shown in fig. 3F). In addition, in some embodiments, the mold 2 can be formed by batch casting, and in order to make the needle 133 penetrate the inner bottom surface of the cavity 20, at least the inner bottom surface of the cavity 20 is made of a material with a hardness less than that of the needle 133, for example, silicone, rubber or other materials are used to make the inner bottom surface of the cavity 20.

In the second embodiment of the present invention, another structure of the mold 4 is adopted, wherein the top surface of the mold 4 is recessed downwards to form at least one cavity 40, and the cavity 40 is divided into an upper chamber portion 401 and a lower chamber portion 402, the upper chamber portion 401 and the lower chamber portion 402 are connected to each other in space, as shown in fig. 5A to 5B and fig. 6, first, the bottom surface of the substrate 11 is moved toward the top surface of a mold 4, so that each microneedle 13 can be inserted into the corresponding cavity 40 (as shown in fig. 5A), and each chamber 40 receives only a single microneedle 13 until the tip 133 of the microneedle 13 is received in the lower chamber portion 402, and the outer surface of the needle tip 133 can contact or substantially contact (substantally) the inner surface of the lower chamber portion 402 (as shown in figure 5B), the needle body 131 can be located in the upper chamber 401, and the outer surface of the needle body 131 does not contact the inner surface of the upper chamber 401; in particular, it is desirable that the outer surface of the tip 133 completely conforms to the inner surface of the lower chamber portion 402 (i.e., referred to as "touching"), but because of tolerances or surface irregularities that occur during the fabrication of the mold 4, the outer surface of the tip 133 may be in close proximity to the inner surface of the lower chamber portion 402 (i.e., referred to as "substantially touching").

As shown in fig. 5C to 5D and fig. 6, a priming operation is performed to prime the transdermally delivered drug 15 into the chamber 40 (as shown in fig. 5C), wherein the transdermally delivered drug 15 can flow into the upper chamber portion 401 to cover the needle body 131, but the transdermally delivered drug 15 is blocked by the needle point 133 and cannot flow into the lower chamber portion 402, i.e., although the outer surface of the needle point 133 substantially contacts the inner surface of the lower chamber portion 402, the gap between the outer surface of the needle point 133 and the inner surface of the lower chamber portion 402 is smaller than the particle size of the transdermally delivered drug 15, so the transdermally delivered drug 15 cannot flow into the lower chamber portion 402. Thereafter, a set period of time is waited until the transdermally delivered drug 15 hardens and becomes secured to the needle body 131; finally, a mold release operation is performed to separate both the transdermal drug delivery 15 and the microneedles 13 from the inner wall surface of the cavity 40 (as shown in fig. 5D), so as to expose the needle tips 133, thereby forming the drug-containing microneedle patch 1. In some embodiments, the mold 4 can be manufactured by an industrial continuous process, and the material is hardened and injection molded at a low temperature, and the material of the mold 4 can be, but not limited to, silicone rubber.

In addition, in other embodiments, because the transdermal drug delivery system 15 is a soft material and has thick characteristics, when the transdermal drug delivery system 15 is injected into the upper chamber 401 in a large amount at one time, the air in the lower chamber 402 cannot be exhausted to form a space without the transdermal drug delivery system 15, so that the transdermal drug delivery system 15 only covers the outer periphery of the needle body 131 and exposes the microneedle patch 1 containing drug of the needle point 133. In addition, since the lower chamber portion 402 can be formed in advance in the mold 4, the mold 4 or the needle point 133 is not damaged when the needle point 133 downwardly extends into the mold 4, and mass productivity and quality can be improved.

In summary, referring to fig. 1 and 2 again, the microneedle patch 1 containing drug of the present invention can increase the mechanical strength and success rate of the microneedles 13, after the hard needlepoint 133 of the microneedles 13 partially punctures the stratum corneum of the skin, the soft drug-containing material coated on the needle body 131 of the microneedles 13 can penetrate into the epidermal tissue under the stratum corneum together with the microneedles 13, so as to achieve the effect of generating drug reaction under the skin, and after the soft drug-containing material is softened and absorbed in the skin for several minutes, the hard portion of the microneedles 13 is pulled out, leaving the active drug component on the skin, thereby completing the drug delivery process of the microneedles 13, and the method for manufacturing the microneedle patch 1 containing drug of the present invention can improve the mass production and the quality of the microneedle 13 products, thereby facilitating the application of the microneedle patch in the future. Accordingly, the above description is only for the preferred embodiment of the present invention, but the scope of the claims of the present invention is not limited thereto, and the equivalent variations can be easily found by those skilled in the art according to the disclosure of the present invention without departing from the protection scope of the present invention.

Claims (9)

1. A microneedle patch containing medicine with exposed needle points at least comprises:

a substrate;

at least one microneedle extending downward from the bottom of the base body, the two microneedles are connected together to form a microneedle patch, wherein the tip of the microneedle is tapered; and

a transdermal drug delivery, which is coated on the outer periphery of the body of the micro-needle to form a micro-needle patch containing the drug and can expose the needle point.

2. The microneedle patch with an exposed needle tip according to claim 1, wherein a longitudinal length from a top side to a bottom side of the microneedle forms a microneedle height, a transverse length of the top side of the microneedle forms a microneedle width, and a ratio of the microneedle height to the microneedle width is 1: 1 to 12: 1.

3. the microneedle patch with exposed needle points according to claim 1, wherein the ratio of the longitudinal height of the microneedle needle points to the needle body is 1: 4 to 1: 10.

4. the drug-containing microneedle patch according to claim 1, wherein the microneedle has an elastic modulus value of 1 GPa to 7 GPa.

5. The microneedle patch according to claim 1, wherein microneedles are inserted into a cavity recessed from a top surface of a mold, the cavity is filled with a transdermally delivered drug, and the microneedle body adheres to the cavity with the transdermally delivered drug and is withdrawn from the cavity, and the recessed cavity is tapered, has an upper cavity portion and a lower cavity portion, or has only a single cavity.

6. The microneedle patch according to claim 5, wherein the top surface of said mold is a single cavity recessed downward, the microneedles of said microneedle patch are inserted into said cavity, and the tips of said microneedles penetrate the bottom surface of said cavity.

7. The microneedle patch with exposed needle points according to claim 6, wherein the bottom surface of the inner side of the single cavity of the mold is made of silicone.

8. The microneedle patch containing drug with an exposed needle tip of claim 5, wherein the upper chamber portion of the mold chamber accommodates the microneedle body of the microneedle patch, and the lower chamber portion of the mold chamber accommodates the microneedle tip of the microneedle patch.

9. The microneedle patch of claim 8, wherein the gap between the outer surface of the needle tip and the inner surface of the lower chamber portion is smaller than the diameter of the drug to be delivered transdermally.

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