Transdermal patch containing fentanyl or salt thereof

Abstract

Provided is a patch containing fentanyl or a derivative thereof which causes no lowering in the stickiness to the skin, has a high drug-stability, can inhibit the time-dependent deposition of fentanyl crystals, yet little irritates the skin and shows an extremely high skin permeability of fentanyl. A patch containing fentanyl or a derivative thereof consisting of a support, a pressure-sensitive adhesive layer containing fentanyl or a derivative thereof and a release liner, wherein the pressure-sensitive adhesive layer containing fentanyl or a derivative thereof contains 0.01 to 0.5% by mass of an ascorbate such as an L-ascorbate palmitate.  A patch containing fentanyl or a derivative thereof which further contains a hindered phenol-type antioxidant in an amount sufficient for the inhibition of the deposition of fentanyl or a salt of the same.

Description

Technical field [0001] The present invention relates to a percutaneously absorbable patch containing fentanyl (chemical name: N-(1-phenethylpiperidin-4-yl)-N-phenylpropionamide) or a salt thereof. The transdermal absorption patch containing fentanyl or its salt provided by the present invention is a preparation that has excellent drug stability over time and does not precipitate fentanyl crystals. The transdermal absorption patch is expected to be used as a long-lasting effect Of anesthetics and analgesics. Background technique [0002] Fentanyl or its citrate is a synthetic opioid analgesic, which is mainly used as an injection for the treatment of acute postoperative pain and chronic cancer pain. In addition, in addition to injections, fentanyl-containing patches have been developed (see Patent Document 1), which has achieved good clinical effects. [0003] The patch has a reservoir type, which has excellent fentanyl sustained-release properties, has a longer action time compar...

AI Technical Summary

Problems solved by technology

On the other hand, the structure of the preparation is composed of a support, a drug storage layer, a release-controlling layer, an adhesive layer, and a liner, and the number of steps to manufacture the preparation is many and complicated, and high-precision technology is required

Therefore, the manufacturing cost becomes higher compared with the usual patch, and improvement is required

[0004] In addition, although the method adopted is to apply one sheet of this preparation continuously for 3 days, there are the following problems: peeling or rolling up during the application process due to insufficient adhesion, crystals of fentanyl due to ethanol volatilization over time change

[0007] Among them, for example, the silicone adhesive base used in Patent Document 2 generally has insufficient adhesiveness to the skin, peels off or rolls up during application, and may not be able to stably administer the drug to cancer patients, that is, may not be maintained. effective plasma concentration of the drug

[0008] In addition, the patch of Patent Document 3 is a preparation with excellent adhesion to the skin, and the alicyclic saturated hydrocarbon resin used for the tackifier resin has low compatibility with fentanyl compared with other tackifier resins, May cause the fentanyl dissolved in the cream layer to recrystallize and precipitate out over time

Furthermore, although the patches of Patent Documents 4 and 5 are patches with good formulation stability and excellent transdermal properties, there may be problems such as sweating, decreased adhesion to the skin when bathing, and skin irritation.

[0009] In order to improve the problem of crystal precipitation in the matrix-type fentanyl percutaneous absorption type patch described above, as an inhibitor of crystal precipitation of fentanyl or its salt, isomyristate in fatty acid alkyl esters as an organic liquid agent is blended. Propyl ester, isostearyl alcohol in saturated or unsaturated long-chain branched alcohols, octyldodecanol, etc., but all will reduce the original adhesiveness of the adhesive base, resulting in peeling off during application or rolled up, the effective blood drug concentration cannot be maintained. In addition, due to the reduction of the cohesiveness of the adhesive base, there is a problem that the residual glue of the paste appears on the skin and the patient's compliance (compliance) decreases.

On the other hand, it is described that in conventional fentanyl transdermal patch preparations, antioxidants such as tocopherol and its ester derivatives, ascorbic acid, stearate, nordihydroguarantee can be blended as optional components. Nordihydroguaiaretic acid, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) (Patent Document 1), the stabilizing effect of these antioxidants on fentanyl or its salts is completely unknown

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