| 摘要 |
<p>#CMT# #/CMT# Transdermal therapeutic system comprises: (a) a backing layer; (b) a pressure-sensitive adhesive matrix layer containing the active substance; and (c) a release liner, where active substance is fentanyl or its analogue including alfentanil, carfentanil, lofentanil, remifentanil and trefentanil or their salts. The matrix layer comprises first polyisobutylene and/or second polyisobutylene as pressure-sensitive adhesive polymer. The first polyisobutylene has storage modulus, which is constant at 10-40[deg] C and second polyisobutylene has storage modulus, which decreases continuously at 10-40[deg] C. #CMT# : #/CMT# Transdermal therapeutic system comprises: (a) a backing layer; (b) a pressure-sensitive adhesive matrix layer containing the active substance; and (c) a release liner, where the active substance is fentanyl or its analogue including alfentanil, carfentanil, lofentanil, remifentanil and trefentanil or their salts. The matrix layer comprises first polyisobutylene and/or second polyisobutylene as pressure-sensitive adhesive polymer. The first polyisobutylene has a storage modulus, whose value is substantially constant at the temperature of 10-40[deg] C and the second polyisobutylene has a storage modulus, whose value decreases continuously at the temperature of 10-40[deg] C with increasing temperature. The storage modulus in the linear visco-elastic region at a frequency of 10 rad/second is measured using a rheometer with parallel plate geometry, where the pressure-sensitive adhesive matrix layer contains undissolved active substance in the form of active substance particles. An independent claim is also included for producing the transdermal therapeutic system, comprising dispersing the active substance in the permeation enhancer, distributing the first and second polyisobutylenes in a solvent, homogeneously mixing the two polymer-containing solutions, where the polymer-containing solutions are mixed with the dispersed active substance, and optionally other ingredients until a uniform mass is obtained, applying the resulting mass to the release liner or the backing layer, removing the solvent, laminating the backing layer or the release liner and cutting or punching the transdermal therapeutic system into desired size. #CMT#USE : #/CMT# The transdermal therapeutic system is useful for administering fentanyl or its analogue through the skin. #CMT#ADVANTAGE : #/CMT# The transdermal therapeutic system: exhibits good skin compatibility, good adhesion up to three days on the skin and improved permeation; ensures sufficient drug release; and can be produced in simple and cost efficient manner. #CMT#PHARMACEUTICALS : #/CMT# Preferred Components: The active substance is fentanyl. The amount of active substance is sufficient for an application period of 3 days, and the concentration of active substance in the matrix layer is 3-15 wt.%, preferably 5-6 wt.%, respectively based on the weight of the matrix layer. #CMT#POLYMERS : #/CMT# Preferred Components: All the values of the storage modulus for first polyisobutylene at 10-40[deg] C differ from the value of the storage modulus at 40[deg] C by not > 50%, preferably by not > 25%. The storage modulus for the second polyisobutylene at 10[deg] C is at least 2 times, preferably at least 3 times the storage modulus at 80[deg] C. The ratio of first polyisobutylene to second polyisobutylene in the matrix layer is 20%:80% to 40%:60%, preferably 25%:75% to 35%:65%, each based on the total weight of first and second polyisobutylenes. The first and second polyisobutylenes are individual polyisobutylenes with different molecular weights. The matrix layer contains a permeation enhancer which is isopropyl myristate or oleyl oleate. The matrix layer contains a tackifier, which is polybutene or hydrogenated or non-hydrogenated colophonium ester. The first and second polyisobutylenes, only a tackifier, preferably polybutene or hydrogenated colophonium ester and a permeation enhancer, preferably oleyl oleate or isopropyl myristate is present in the adhesive matrix layer adjacent to the active substance. The amount of the tackifier is 23-28 wt.%, based on the total weight of the matrix layer, and the permeation enhancer is present in an amount 8-15 wt.%, based on the total weight of the matrix layer. #CMT#EXAMPLE : #/CMT# 0.6 g Fentanyl was dispersed in 1 g isopropyl myristate. The mixture was stirred until a homogeneous suspension was obtained. 5.58 g Duro-tak 87-626A(RTM: Pressure-sensitive adhesive) and 14.48 g Durotak 87-625A(RTM: Pressure-sensitive adhesive) were added with stirring over a period of 20 minutes to the mixture of fentanyl and isopropyl myristate. Subsequently 2.52 g polybutene was added to the remaining mixture. The mixture was stirred until a homogeneous coating mass was obtained. This homogeneous coating composition was coated on film of Scotchpak 9742(RTM: Release liner) at a thickness of 117 mm. The mixture was then gradually heated to 50[deg] C, 60[deg] C, 70[deg] C and 80[deg] C and dried, to obtain matrix layer. The dried matrix was laminated with backing layer of Scotchpak 9723(RTM: Polyester film laminate) to obtain plaster fragments, which were punched into a suitable size of the laminate.</p> |
