KR20200049363A - Ropinirole percutaneous drug delivery system - Google Patents

Abstract

Disclosed is a percutaneous absorption agent for treating Parkinson′s disease containing ropinirole. The percutaneous absorption agent containing ropinirole of the present invention has a fast initial drug release speed, allows continuous release, inhibits discoloration, has high stability, has no crystal precipitation, is easy for storage and use, and is easy to manufacture.

Description

Ropinirole percutaneous drug delivery system

The present invention relates to a transdermal absorber for the treatment of Parkinson's disease containing ropinirole.

Parkinson's disease is one of neurodegenerative diseases, and is known to occur because dopamine is not produced. Therefore, it is known that supplying a dopamine precursor to the body is very important for the treatment of Parkinson's disease and has the strongest effect.

As a representative drug of the dopamine precursor having such a powerful effect is levodopa (levodopa). Levodopa significantly improves movement disorders that are common in Parkinson's disease, such as tremor, swelling, and stiffness. However, when long-term administration of levodopa for 5 years or more, there is a disadvantage in that symptoms of dyskinesia occur due to a phenomenon of 'loss of efficacy' in which 50% of patients have a shorter duration of drug efficacy.

Therefore, it should be considered the most important thing in the treatment of Parkinson's disease to delay the administration time for the dopamine precursor as much as possible, and to minimize the dosage to delay the time when the 'effect loss' occurs.

Ropinirole is a second-generation dopamine agonist, which enters the brain and directly stimulates dopamine receptors to improve the symptoms of movement disorders in Parkinson's disease. In addition, it is possible to alleviate the effect of dopamine loss, and there are few exercise complications, so it is mainly used in the treatment of early Parkinson's patients, and in severe cases, it can be administered in combination with levodopa.

Since Parkinson's disease suffers from cognitive impairment, it is often impossible to regularly take therapeutic drugs, thereby exacerbating Parkinson's disease.

If the Parkinson's disease treatment drug is administered in the form of a transdermal absorbent such as a patch, it is used once a day to improve the convenience of taking the drug, and it is easier to continuously inject the drug, thereby increasing the treatment effect of Parkinson's disease and cognizing the patient By reducing the likelihood of dysfunction, the patient's quality of life can be improved.

In addition, in order to prevent cognitive decline in cognitive function of Parkinson's disease, it is important to prevent the expression of resistance of the drug itself, but it is also important to keep the blood concentration of the therapeutic drug constant. Therefore, by keeping the drug concentration in the blood constant, the patient can continuously maintain cognitive function.

Particularly, the time period during which cognitive dysfunction occurs most frequently is an empty time until the first medicine taking time after wake-up, which means taking medication in the evening and until the morning wake-up time, there is no new drug supplied to the body, so the drug blood concentration drops. Because it happens.

In order to improve this problem, it is possible to reduce the possibility of cognitive dysfunction in the patient by maintaining the blood concentration of the active ingredient by administering the drug through the transdermal absorption formulation, and also maintaining the blood concentration with or without sleep. Therefore, the development of such a transdermal absorption formulation can improve the patient's compliance with the dose and reduce the cognitive decline time, thereby improving the life satisfaction of the carer as well as the patient himself.

As a prior art for transdermal absorption formulation of ropinrol, Korean Patent Publication No. 10-2014-0034814 discloses a configuration using a metal ion dechlorinating agent to increase stability, but sodium hydroxide used as a dechlorinating agent is a polymer It can remain in the adhesive and dissolve the dead skin cells and cause skin damage, and the compatibility with rubber may be low, resulting in a homogeneity problem in the matrix.

Korean Patent Publication No. 10-2014-0034814

The present inventors confirmed that a problem of discoloration and crystal precipitation occurs depending on the adhesive and excipients used when preparing a transdermal absorbent containing a raffinirol vitreous (free base) or a pharmaceutically acceptable salt thereof. .

As a result, the present inventors have studied a method for improving the crystal precipitation and discoloration problems, and confirmed that the crystal precipitation problem and the discoloration problem can be solved through a percutaneous absorbent having a new composition different from the prior art as described above.

Accordingly, the present invention is to provide a percutaneous absorber containing ropinirole that does not cause crystal precipitation problems and discoloration problems.

In order to solve the above problems, the transdermal absorbent containing ropinirol of the present invention includes a drug-containing adhesive layer, a support layer, and a release layer, wherein the drug-containing adhesive layer is ropinirol or a pharmaceutically acceptable salt and acrylic system thereof. It contains a polymer adhesive. The transdermal absorbent of the present invention contains C8 to C18 fatty acids or derivatives thereof in the adhesive layer, thereby providing excellent skin permeability of ropinrol, securing sufficient adhesiveness, suppressing discoloration over time, and improving stability, No crystal is deposited.

The content of the ropinirol and / or its pharmaceutically acceptable salt in the transdermal absorber containing ropinirol of the present invention is 5 to 25% by weight, preferably 15, based on the total mass of the adhesive layer when converted to the ropinirol vitreous body It is ~ 20% by weight.

The transdermal absorber containing ropinirol of the present invention further includes a transdermal absorption enhancer. As such a transdermal absorption enhancer, C8 to C18 fatty acids or derivatives thereof may be used. The fatty acids of C8 to C18 or derivatives thereof, one or more selected from the group consisting of oleic acid, stearic acid, palmitic acid, lauric acid, sorbitan monooleate, propylene glycol monolaurylate, glycol monooleate, etc. Can be. The fatty acid is preferably contained in an amount of 0.5 to 2 equivalents to 1 equivalent of ropinirole or a pharmaceutically acceptable salt thereof in view of the effect of suppressing discoloration.

On the other hand, when a material having a high molecular weight such as fatty acids is used, in order to maintain an appropriate equivalent ratio to ropinirole or a pharmaceutically acceptable salt thereof, the weight of the fatty acid used is inevitably increased. Since the relative content ratio is reduced, the percutaneous absorbent may not maintain the form, thereby deteriorating stability, and the input of other excipient components may be limited.

At this time, when using a pH adjusting agent, it is possible to solve the problems as described above. That is, when using a pH adjusting agent such as ascorbic acid, citric acid, sodium citrate, sodium hydrogen phosphate, sodium dihydrogen phosphate, acetic acid, sodium acetate, triethyl citrate, glycerin, oleyl alcohol, the effect of inhibiting discoloration and suppressing crystal precipitation While achieving it, it is possible to reduce the weight of the fatty acid to increase the content of the pressure-sensitive adhesive relatively, and accordingly, even when the pressure-sensitive adhesive layer is in contact with the skin, while maintaining its shape, it can exhibit a discoloration-inhibiting effect.

The present invention may further include a solubilizing agent such as a surfactant in the adhesive layer. As such a solubilizing agent, propylene glycol, propylene glycol monocaprelate, propylene glycol monolaurate, propylene glycol ricinoleide, propylene grillol monoolee Eight, propylene grill call dicaprelate, propylene glycol dioctanoate, and the like can be used, and may contain 0.3 to 1.5 parts by weight based on 1 part by weight of the free form of lopinirol or a pharmaceutically acceptable salt thereof.

The transdermal absorbent containing ropinirole of the present invention has a high initial drug release rate, allows continuous release, suppresses discoloration, has high stability, has no crystal precipitation, is easy to store and use, and is easy to manufacture. In addition, since the relative content of the adhesive base is not reduced, the shape can be stably maintained even when the adhesive layer is in contact with the skin. In addition, the transdermal absorbent of the present invention can be used as a therapeutic agent for Parkinson's disease because it greatly improves patient compliance with oral medications and improves cognitive impairment.

1 shows the effect of preventing discoloration of the present invention.
Figure 2 shows the effect of inhibiting crystal formation of the present invention.
3 is a graph showing the skin permeation rate of ropinirole of the present invention.
4A and 4B are photographs taken with a microscope to confirm the presence or absence of crystal formation in the present invention (magnification X850).
5 is a graph showing the change in the percutaneous absorption rate according to the ratio of the percutaneous absorption enhancer of the present invention.
6 is a graph showing changes in percutaneous absorption rate according to the use of the percutaneous absorption enhancer of the present invention.
7 schematically shows a cross-section of the transdermal absorbent of the present invention.

The present invention relates to a transdermal absorbent comprising ropinrol or a pharmaceutically acceptable salt thereof as an active ingredient.

More specifically, the present invention relates to a transdermal absorber comprising ropinirol or a pharmaceutically acceptable salt thereof as an active ingredient, (a) ropinirol or a pharmaceutically acceptable salt thereof as an active ingredient; And a drug-containing adhesive layer containing an acrylic polymer adhesive. (b) a support layer; And (c) a release layer.

In the present invention, the drug-containing adhesive layer may further include excipients such as a transdermal absorption enhancer, an antioxidant, a pH adjusting agent, and a dissolution aid, in addition to lopinirol or a pharmaceutically acceptable salt and adhesive.

In the present invention, it is preferable from the aspect of improving the percutaneous absorption rate that a ropinirol free base is used rather than a salt of rofinirol as an active ingredient. Therefore, a ropinerol vitreous is used as a raw material to be used. When the salt of ropinrol is used as a raw material, a process of removing the salt is added and cumbersome, and there is a risk of skin irritation and damage due to the residue of the neutralization reaction.

In the present invention, the ropinirol or a salt thereof is 5 to 25% by weight, preferably 15 to 20% by weight, more preferably 16 to 19% based on the total weight of the drug-containing adhesive layer, based on the ropinirol vitreous body It may be included in weight percent. When the content of the drug relative to the total weight of the drug-containing adhesive layer is less than 5% by weight, the concentration gradient of the main component is weak, and the percutaneous absorption rate of the drug is weakened. When the content of the drug exceeds 25% by weight, the relative weight ratio of the adhesive after drying There is a difficulty that the structure of the pressure-sensitive adhesive collapses because it is lowered.

The pressure-sensitive adhesive used in the present invention may be any pressure-sensitive adhesive, but it is preferable to use an acrylic pressure-sensitive adhesive. In the present invention, the acrylic pressure-sensitive adhesive is an acrylic polymer made from the synthesis of an acrylic monomer or a vinyl acetate-based monomer and an acrylic monomer, and (i) having no functional group, (ii) having a hydroxyl (-OH) group as a functional group , (iii) one or more selected from the group consisting of having a carboxyl (-COOH) group as a functional group, and (iv) having both a hydroxyl group (-OH) and a carboxyl group (-COOH) as a functional group. have. Preferably, an acrylic pressure sensitive adhesive having a carboxyl group (-COOH) is used as a functional group, or a functional group having both a carboxyl group (-COOH) and a hydroxyl group (-OH) can be used. When a pressure-sensitive adhesive having a carboxyl group (-COOH) or a pressure-sensitive adhesive having both a carboxyl group and a hydroxyl group is stirred with ropinrol, the color retention time is relatively long. However, when mixed alone with an adhesive having no functional group or a hydroxyl group (-OH), the color rapidly changed to red.

As the transdermal absorption enhancer in the present invention, fatty acid or fatty acid alcohols of C8 to C18, fatty acid ethers, or fatty acid derivatives such as fatty acid esters, pyrrolidone derivatives, polyalcohol esters, and the like can be used. Preferably, one or more fatty acids, such as oleic acid, palmitic acid, stearic acid, and lauric acid, which have a discoloration inhibitory effect, may be selected and used. The fatty acid is preferably contained in an equivalent of 0.5 to 2 relative to 1 equivalent of lopinirol or a pharmaceutically acceptable salt thereof. When the transdermal absorption enhancer is included in an excess of 2 equivalents, it may result in a decrease in the physical strength of the transdermal absorption agent, and in some cases may cause skin troubles of the user.

The present invention may include an antioxidant to inhibit the decomposition and denaturation of lopinirol or a pharmaceutically acceptable salt. Antioxidants include Butyl hydroxy toluene, Butyl hydroxy anisole, Propyl galate, Ascorbic acid, Tocopherol, Coperol Acetate ( Tocopherolacetate), ascorbyl palmitate, cetylpyridinium chloride, or the like may be used, and one or more selected from the group consisting of butylhydroxytoluene, tocopherol, and tocopherol acetate may be used. do. Antioxidants can be used to be 0.1 to 5% by weight relative to the total weight of the drug-containing adhesive layer, preferably 0.1 to 1% by weight. When the antioxidant is used in an amount of 5% by weight or more, the antioxidant effect is no longer improved.

In the present invention, the support layer uses a thin, flexible and non-allergic reaction to the skin in order to prevent loss of the main component from the formulation while attached to the skin or while the product is distributed and stored. As the support layer, materials such as polyethylene terephthalate (PET), polyethylene (PE), polypropylene (PP), ethylene vinyl acetate copolymer (EVA), nylon, and cotton can be used, and the shape of the support layer Can be used alone or a combination of two or more fabrics and films, a combination of a nonwoven fabric and a film, and a combination of a film and a film. Preferably, a polyethylene terephthalate (PET) material is used to prevent the drug from being transferred to the support layer, and the form uses a film or a non-woven fabric and a combination of films to prevent contact with water vapor in oxygen or air. Also, for shading, an aluminum thin film may be laminated in the middle or aluminum may be deposited on the film surface.

In the present invention, the release layer is not particularly limited as long as it protects the drug-containing product while the product is packaged or distributed and stored, and provides convenience so that it can be easily removed when the product is used. Polyester, polyvinyl chloride, poly As a film or paper manufactured from vinylidene chloride, polyethylene terephthalate, polyethylene, ethylene vinyl acetate, etc., a film laminated with high-quality paper or glassine paper and polyolefin may be used. The release film is coated with a silicone resin or a fluorine resin on the surface contacting the adhesive layer, and the film used for the release layer can also be laminated with an aluminum thin film in the middle for light shielding or aluminum can be deposited on the film surface.

[Example]

Hereinafter, the present invention will be described in detail in Examples. However, the following examples are merely illustrative of the present invention, and the contents of the present invention are not limited to the following examples.

Example  One:

Ingredient Control 1 Test group 1 Lopinirol vitreous 9.2% 9.2% Oleic acid 2.0% 10.0% Acrylic adhesive (-COOH) 88.8% 80.8% Sum 100.0% 100.0% (* In the composition of Test Group 1, 1 equivalent of oleic acid was used relative to 1 equivalent of ropinirol vitreous)

A transdermal absorber having a drug-containing adhesive layer having the composition of the above table is prepared by the following method:

Oleic acid is added to the acrylic adhesive and stirred sufficiently. After confirming the homogeneity of the solution, to this, a lopinirol vitreous was added and completely dissolved. The prepared solution was applied to a release paper (peel layer) using an applicator, dried in an oven at 80 ° C. for 3 minutes, laminated the support layer film, compressed using a compaction roller, and then a percutaneous absorbent having an area of 4 cm 2 was obtained using a patch cutter. It was produced. As a result of observing the degree of discoloration by leaving the transdermal absorbent prepared as above at room temperature for 2 months, it was observed that the color of the patch was changed to red in the control group 1 without sufficient amount of oleic acid, but discoloration was not observed in the test group 1. No, it was confirmed that the initial color was maintained (see Fig. 1).

It was confirmed that the color change of the patch was due to the ropinirole, and the color gradually turned red as the stability of the ropinirole decreased in initial light yellow or light brown.

Example  2:

Composition Control 2 Control 3 Test group 2 Test group 3 Lopinirol vitreous 4.4% 9.2% 13.6% 17.6% Oleic acid 4.8% 10.0% 14.8% 19.2% Acrylic adhesive (-COOH) 90.8% 80.8% 71.6% 63.2% Sum 100.0% 100.0% 100.0% 100.0%

A transdermal absorber having a drug-containing adhesive layer having the composition of the above table is prepared by the following method:

The control methods 2 and 3 and test groups 2 and 3 were prepared in the same manner as in Example 1.

In general, as the weight ratio of the main component in the transdermal absorbent increases, crystals may be formed and also affect the release rate of the drug.

It was confirmed that commercial use is possible by maintaining crystal formation inhibition in both the case where the weight ratio of the main component used in the transdermal absorbent of the present invention is about 5% by weight and 17.6% by weight. In addition, when the ratio of fatty acids was 0.5 to 2 equivalents to 1 equivalent of ropinirole, it was confirmed that discoloration was suppressed even after 2 months in the same manner as in Example 1 (see FIG. 2).

However, when the weight ratio of the main component is increased as in test groups 2 and 3, the absorption rate can be improved (see FIG. 3).

Example  3:

Composition Test group 4 Test group 5 Lopinirol vitreous 17.6% 17.6% Oleic acid 19.2% 8.0% Sodium acetate 0.4% Acetic acid 0.4% Antioxidant 1.6% 0.1% Acrylic adhesive (-COOH) 61.6% 73.5% Sum 100.0% 100.0%

Test group 4 was prepared in the following manner: Oleic acid and antioxidant were added to the acrylic adhesive, followed by stirring sufficiently. After confirming the homogeneity of the solution, to this, a ropinirole vitreous was added and completely dissolved. The thus prepared solution was applied to a release paper (peel layer) using an applicator, dried in an oven at 80 ° C. for 3 minutes, laminated the support layer film, compressed using a compaction roller, and then a percutaneous absorbent having an area of 4 cm 2 was used with a patch cutter. It was produced. The transdermal absorber thus prepared was exposed to room temperature to confirm the presence or absence of crystal formation.

Test group 5 was prepared by the following method: sodium acetate and acetic acid, which are pH adjusting agents, were first placed in the appropriate amount of ethanol, and then thoroughly stirred to dissolve completely. To this, an acrylic adhesive, oleic acid, and antioxidant were added to mix evenly. After confirming the homogeneity of the solution, a ropinirol vitreous body is added thereto to dissolve, and the thus prepared solution is applied to release paper using an applicator and dried completely through ethanol through a drying process to prepare a transdermal absorbent. The transdermal absorber thus prepared was exposed to room temperature to confirm the presence or absence of crystal formation.

In the test groups 4 and 5, it was confirmed that crystals were not formed in the drying process, and crystals were not formed even when left at room temperature for 2 months (see FIGS. 4A and 4B).

Particularly, when a small amount of the pH adjusting agent is added as in Test Group 5, the amount of fatty acids can be reduced, thereby increasing the relative weight ratio of the pressure-sensitive adhesive to prepare a stable form of a transdermal absorber, and at this time, the effect of discoloration suppression and determination The inhibitory effect is still maintained.

Example  4:

Composition Control 4 Test group 6 Test group 7 Test group 8 Test group 9 Lopinirol vitreous 17.6% 17.6% 17.6% 17.6% 17.6% Oleic acid 0% 38.4% 19.2% 9.6% 9.6% BHT (antioxidant) 0.88% 0.88% 0.88% 0.88% 0.88% Propylene glycol monolaurate
(Dissolution aid) 5% Acrylic adhesive (-COOH) 81.52% 43.12% 62.32% 71.92% 66.92% Sum 100% 100% 100% 100% 100%

Example 4 was prepared in a similar manner to Example 3.

The fatty acids used in the present invention are not merely transdermal absorption enhancers, but also have a function of preventing discoloration, and thus must include fatty acids.

However, if the content of the active ingredient is increased for a sufficient transdermal absorption rate, the content of fatty acids should also be increased accordingly (the content ratio of fatty acid is about 0.5 to 2.0 equivalents based on 1 equivalent of the free weight of the active ingredient). However, as the weight ratio of fatty acids increases, the relative weight ratio of the pressure-sensitive adhesive (acrylic pressure-sensitive adhesive) decreases, resulting in unstable shape.

At this time, when a solubilizing agent is included in addition to the fatty acid as in the test group 9, the transdermal permeability of the drug is not lowered even if the content of the fatty acid is lowered, and discoloration suppression can be maintained. On the other hand, it can be seen that in the control group 4, drug release was hardly achieved, and thus, it could not be actually used (see FIG. 5).

Specifically, referring to FIG. 5, when looking at the permeability of the test groups 6 to 8, it can be seen that the higher the amount of oleic acid used, the higher the permeability. However, when a dissolution aid is used as in Test Group 9, it can be seen that the amount of oleic acid used is at least high in transdermal permeability. In addition, as the amount of oleic acid is reduced, the relative content ratio of the pressure-sensitive adhesive increases, thereby improving the morphological stability of the formulation. That is, in Test Group 9, the content ratio of the percutaneous absorption accelerator is much lower than that in Test Group 6, but has a similar percutaneous permeability value as Test Group 6. On the other hand, since the content of the adhesive in the test group 9 is much higher than that in the test group 6, the stability of the form is excellent in the test group 9.

Example  5:

Composition Test group 7 Test group 10 Test group 11 Lopinirol vitreous 17.60% 17.60% 17.60% Oleic acid 19.20% 9.60% 5.04% Propylene glycol monolaurate
(Dissolution aid) 2.56% 5.04% Sodium acetate 0.41% Acetic acid 0.37% Antioxidant (BHT) 0.88% 0.08% 0.1% Acrylic adhesive (-COOH) 62.32% 70.16% 71.44% Sum 100% 100% 100%

Test groups 10 and 11 of Example 5 were prepared in a similar manner to Example 3 or 4.

In test group 10, oleic acid was used at a content of 9.6%, and in test group 7, oleic acid was used at a content of 19.2%. That is, the amount of oleic acid used in test group 10 was only half of the amount of oleic acid used in test group 7. Nevertheless, the results of the percutaneous absorption test of Test Group 7 and Test Group 10 show similar values for total emission at 24h. Therefore, when using a combination of a percutaneous absorption enhancer and a dissolution aid, as in Test Group 10, it was confirmed that a small amount of a transdermal absorption enhancer can be used while exhibiting an equivalent drug release effect compared to the case where a percutaneous absorption enhancer is used alone. Did.

In addition, in the test group 10, the relative content of the pressure-sensitive adhesive increases as the content of the transdermal absorption enhancer decreases. However, despite the increase in the content of the pressure-sensitive adhesive, a phenomenon in which drug release decreases was not observed. There is an advantage that the form of the formulation remains stable.

As shown in the result of the transdermal absorption test of Test Group 11, it can be seen that even when the content ratio of oleic acid is reduced and the content ratio of the adhesive agent is increased by adding a pH adjusting agent and a dissolution aid, the release rate of the drug does not drop.

Therefore, in the present invention, by increasing the content ratio of the pressure-sensitive adhesive and reducing the content ratio of the absorption accelerator used while increasing the release rate of the drug, while maintaining the morphological stability of the formulation, preparation of a patch having an excellent drug release rate Is possible.

7 schematically shows a cross-section of the transdermal absorbent of the present invention, A is a support layer, B is a drug-containing adhesive layer, and C is a release layer.

[Method of measuring percutaneous absorption used in the above experiment]

A phosphate buffer (Phosphate buffered saline solution, PBS solution pH = 7.4) was added as a receptor in a Franz-type diffusion cell and maintained at 32 ° C similar to the skin temperature and stirred at a rate of 600 rpm with a magnetic stirrer. The mixture was stirred constantly to remove dissolved gas in the solution. Thereafter, a patch cut to fit the upper donor cell of the Franz type diffusion mechanism was attached to a membrane for transdermal absorption (Strat-M, Merck KGaA, Darmstadt, Germany) and mounted on a Franz type diffusion mechanism. After that, the solution of the receptor part was collected at regular intervals, and a new buffer solution was added as much as the collected amount. The collected sample was analyzed by liquid chromatography (HPLC) and the analysis conditions are as follows.

[Analysis condition]

Detection wavelength: 250nm

Flow rate: 1ml / min

Column size: 4.6 x 250 5um C-8

Column temperature: 30 ℃

Mobile phase: 2.53 mM disodium hydrogen phosphate (adjusted with pH 7.0 phosphoric acid): methanol = 25: 75

Injection volume: 20 μl

Claims (12)

(a) Ropinirol as an active ingredient or a pharmaceutically acceptable salt thereof; And a drug-containing adhesive layer containing an acrylic polymer adhesive.
(b) support layer,
(c) A transdermal absorber comprising a release layer. The method of claim 1, wherein the drug-containing adhesive layer is a transdermal absorber, characterized in that it further comprises a transdermal absorption enhancer. The transdermal absorber of claim 2, wherein the drug-containing adhesive layer further comprises a pH adjusting agent. The acrylic polymer adhesive base according to any one of claims 1 to 3, (i) having a carboxyl group (-COOH) as a functional group, and (ii) a carboxyl group (-COOH) and a hydroxyl group ( -OH) Percutaneous absorbent, characterized in that at least one selected from the group consisting of all. The transdermal absorption enhancer according to claim 2, wherein the transdermal absorption enhancer is a fatty acid of C8-C18 or a derivative or surfactant. The method of claim 2, wherein the transdermal absorption enhancer is selected from one or more groups of oleic acid, palmitic acid, stearic acid, lauric acid, sorbitan monooleate, propylene glycol monolaurylate, and monoolein saglycol. Percutaneous absorbent characterized by. The percutaneous absorption enhancer of claim 2, wherein the transdermal absorption enhancer contains 0.5 to 2 equivalents based on 1 equivalent of ropinirole vitreous. The method of claim 3, wherein the pH adjusting agent is ascorbic acid, citric acid, sodium citrate, sodium hydrogen phosphate, citric acid Triethyl, A transdermal absorber, characterized in that at least one is selected from the group consisting of glycerin, oleyl alcohol, acetic acid, and sodium acetate. According to claim 2 or claim 3, wherein the drug-containing adhesive layer further comprises an antioxidant,
The antioxidant, one or more selected from the group consisting of butyl hydroxy toluene, butyl hydroxyanisole, propyl gallate, ascorbic acid, tocopherol, tocopherol acetate, ascorbyl palmitate, cetylpyridinium chloride Percutaneous absorbent made. The transdermal absorber according to claim 2 or 3, wherein the drug-containing adhesive layer further comprises a dissolution aid. The method of claim 10, wherein the solubilizing agent is propylene glycol, propylene glycol monocaprelate, propylene glycol monolaurate, propylene glycol ricinoleide, propylene grill call monooleate, propylene grill call dicaprelate, propylene glycol diocta A drug-containing adhesive layer capable of using noate, etc., is a transdermal absorber, further comprising a pH adjusting agent. The transdermal absorber of claim 10, wherein the dissolution aid is a surfactant.

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