Asenapine-containing adhesive patch

Abstract

An object of the present invention is to provide an asenapine-containing patch having excellent sustained-release properties while enhancing skin permeability by using a silicone-based pressure-sensitive adhesive base. The present invention relates to a patch having a support and a pressure-sensitive adhesive layer, wherein the pressure-sensitive adhesive layer comprises asenapine and/or a pharmaceutically acceptable salt thereof, a silicone-based pressure-sensitive adhesive base and a release control agent, and the ratio of the maximum skin permeation rate of asenapine to the minimum skin permeation rate from the time when the maximum skin permeation rate is reached to 24 hours is less than 1.62.

Claims

1. A patch comprising a support and a pressure-sensitive adhesive layer, wherein the pressure-sensitive adhesive layer comprises asenapine and/or a pharmaceutically acceptable salt thereof, a silicone-based pressure-sensitive adhesive base, and a release control agent selected from the group consisting of oleic acid, magnesium aluminometasilicate, methacrylic acid-methacrylate copolymers, N-methyl-2-pyrrolidone, and (meth)acrylate (co)polymers, and wherein the ratio of the maximum skin permeation rate of asenapine to the minimum skin permeation rate from the time when the maximum skin permeation rate is reached to 24 hours is less than 1.62.

2. The patch according to claim 1, wherein the silicone-based pressure-sensitive adhesive base is an amine-compatible silicone-based pressure-sensitive adhesive base.

3. The patch according to claim 1, wherein the silicone-based pressure-sensitive adhesive base comprises at least one selected from the group consisting of high-tack amine-compatible silicone-based pressure-sensitive adhesive bases, medium-tack amine-compatible silicone-based pressure-sensitive adhesive bases and low-tack amine-compatible silicone-based pressure-sensitive adhesive bases.

4. The patch according to claim 3, wherein the silicone-based pressure-sensitive adhesive base comprises a high-tack amine-compatible silicone-based pressure-sensitive adhesive base and a medium-tack amine-compatible silicone-based pressure-sensitive adhesive base.

5. The patch according to claim 1, wherein the content of the silicone-based pressure-sensitive adhesive base in the pressure-sensitive adhesive layer is 72 mass % to 96 mass %.

6. The patch according to claim 1, wherein the release control agent is at least one selected from the group consisting of oleic acid and magnesium aluminometasilicate, and wherein the content in the pressure-sensitive adhesive layer is 2.5 mass % to 7.5 mass %.

7. The patch according to claim 1, wherein the release control agent is at least one selected from the group consisting of methacrylic acid-methacrylate copolymers and N-methyl-2-pyrrolidone, and wherein the content in the pressure-sensitive adhesive layer is 1.0 mass % to 5.0 mass %.

8. The patch according to claim 1, wherein the release control agent is at least one selected from the group consisting of (meth)acrylate (co)polymers, and wherein the content in the pressure-sensitive adhesive layer is 12 mass % to 25.0 mass %.

Description

EXAMPLES

Example 1. Preparation of Patch

(1) Patches 1 to 20 consisting of the bases, drug concentration, and additives shown in Table 1 were prepared. Here, asenapine (free form) of 3.2 mass % with respect to the pressure-sensitive adhesive layer was added to each patch, and the mass of the pressure-sensitive adhesive was 100 g/m.sup.2 (set value).

(2) The meanings of the abbreviations in Table 1 are as follows.

(3) <Base>

(4) PSA7-4102: BIO-PSA® 7-4102 Silicone Adhesive (Dow Corning Corp.)

(5) PSA7-4202: BIO-PSA® 7-4202 Silicone Adhesive (Dow Corning Corp.)

(6) PSA7-4302: BIO-PSA® 7-4302 Silicone Adhesive (Dow Corning Corp.)

(7) <Additive>

(8) L-100: Eudragit® L100 (Evonik Industries)

(9) NMP: N-methyl-2-pyrrolidone

(10) 900A: DURO-TAK® 87-900A (Henkel Corporation)

(11) 2510: DURO-TAK® 87-2510 (Henkel Corporation)

Example 2. In Vitro Skin Permeation Test

(12) A 2.5-cm.sup.2 patch was applied to the stratum corneum side of a skin removed from a hairless mouse, and the skin was attached to a flow-through type diffusion cell kept at 32° C. such that the dermis side was on the receptor tank side. In the test, liquid was collected every 4 hours while replacing the phosphate buffered saline in the receptor tank. The drug concentration in the obtained liquid was measured by high performance liquid chromatography. The amount of permeated drug at each time was calculated from the concentration value, and the skin permeation rate of the drug was calculated, then the maximum skin permeation rate Jmax (μg/h/cm.sup.2) was determined.

(13) Similarly, the minimum skin permeation rate (Jmin (μg/h/cm.sup.2)) from the time when the maximum skin permeation rate was reached (Tmax) to 24 hours was determined.

(14) The ratio of the maximum skin permeation rate to the minimum skin permeation rate from the time when the maximum skin permeation rate was reached to 24 hours (Jmax/Jmin (up to 24 hours after Tmax)) was calculated; the results are shown in Table 1.

(15) TABLE-US-00001 TABLE 1 Jmax/Jmin (up to 24 h after Patch Base Drug concentration Additive Tmax) 1 94.3% PSA7-4202 3.2% (free form) 2.5% Oleic acid 1.224 2 94.3% PSA7-4202 3.2% (free form) 2.5% Mg 1.427 aluminometasilicate 3 91.8% PSA7-4202 3.2% (free form) 5.0% Mg 1.320 aluminometasilicate 4 89.3% PSA7-4202 3.2% (free form) 7.5% Mg 1.400 aluminometasilicate 5 95.8% PSA7-4202 3.2% (free form) 1.0% L-100 1.381 6 93.8% PSA7-4202 3.2% (free form) 3.0% L-100 1.403 7 91.8% PSA7-4202 3.2% (free form) 5.0% L-100 1.337 8 95.8% PSA7-4202 3.2% (free form) 1.0% NMP 1.469 9 93.8% PSA7-4202 3.2% (free form) 3.0% NMP 1.600 10 91.8% PSA7-4202 3.2% (free form) 5.0% NMP 1.615 11 84.7% PSA7-4202 3.2% (free form) 12.1% 900A 1.296 12 72.6% PSA7-4202 3.2% (free form) 24.2% 900A 1.126 13 84.7% PSA7-4202 3.2% (free form) 12.1% 2510 1.236 14 72.6% PSA7-4202 3.2% (free form) 24.2% 2510 1.067 15 94.3% PSA7-4202 3.2% (free form) 2.5% Oleyl alcohol 1.823 16 94.3% PSA7-4202 3.2% (free form) 2.5% Propylene glycol 1.638 17 94.3% PSA7-4202 3.2% (free form) 2.5% Myristyl alcohol 1.718 18 96.8% PSA7-4102 3.2% (free form) None 1.631 19 96.8% PSA7-4202 3.2% (free form) None 1.812 20 96.8% PSA7-4302 3.2% (free form) None 1.709

(16) As an additive, when oleic acid (patch 1), magnesium aluminometasilicate (patches 2 to 4), Eudragit® L100 (patches 5 to 7), N-methyl-2-pyrrolidone (patches 8 to 10), DURO-TAK® 87-900A (patches 11 and 12), and DURO-TAK® 87-2510 (patches 13 and 14) were used, Jmax/Jmin (up to 24 hours after Tmax) values were less than 1.62; and for the above-mentioned patches 1 to 14, Jmax/Jmin (up to 24 hours after Tmax) values were less than 1.43 except for N-methyl-2-pyrrolidone (patches 8 to 10).