Nisoldipine ethosome controlled-released patch and preparation method thereof

Abstract

The invention relates to a nisoldipine ethosome controlled-released patch and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The nisoldipine ethosome controlled-released patch consists of a back lining, a frame type medicated storage cavern layer and an anti-adhesion layer, and the frame type medicated storage cavern layer contains nisoldipine ethosomes, pressure-sensitive adhesives, penetration enhancer, crosslinking agents, plasticizer and humectants. The ethosomes serve as transdermal drug delivery carriers, percutaneous permeation of the nisoldipine is improved, release of drug is controlled by the frame type pressure-sensitive adhesives, and the nisoldipine transdermal delivery patch is prepared. Compared with a nisoldipine oral preparation, the nisoldipine ethosome controlled-released patch can overcome shortcomings that a first-pass effect of oral delivery is obvious, bioavailability is low, and untoward effects of a digestive tract are obvious. Compared with a common nisoldipine patch, the nisoldipine ethosome controlled-released patch has the advantages that a controlled-released characteristic is good in a percutaneous penetration process, the percutaneous penetration rate of drug is increased for five times at least, stable high blood concentration can be maintained for a long time, relative bioavailability is improved for 4 times almost.

Description

technical field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and relates to a transdermal drug delivery preparation for treating cardiovascular diseases, in particular to a nisoldipine ethosome controlled-release patch and a preparation method thereof. Background technique

[0002] Nisoldipine (nisoldipine) is a new type of dihydropyridine calcium channel blocker. Its chemical structure is similar to that of nifedipine. The carboxylate methyl group at the 3 or 5 position of nifedipine is replaced by carboxy isobutyl, and its fat solubility is enhanced. , the pharmacological effect is 4 to 10 times that of the latter, and it is one of the strongest calcium antagonists known so far. Its main pharmacological action is to inhibit Ca 2+ Enter the excitatory cells, selectively cause the expansion of peripheral blood vessels and coronary vessels, but have no effect on myocardial contractility and cardiac conduction system. Nisoldipine can al...

Examples

Embodiment 1

[0038] The nisoldipine elastosome controlled-release patch is composed of a backing layer, a skeleton drug-containing reservoir layer and an anti-adhesive layer, and its preparation method is as follows:

[0039] (1) Accurately weigh 0.4g of nisoldipine, 3.0g of phospholipids and 0.3g of cholesterol, add 45ml of absolute ethanol and stir until completely dissolved, under rapid stirring conditions, slowly drop into an aqueous solution containing 0.2% glacial acetic acid kept at 30°C In 55ml, the crude ethosome was obtained, ultrasonically dispersed for 30min, and then filtered through a 0.22 μm microporous membrane to obtain nisoldipine ethanol body fluid with uniform particle size.

[0040] (2) Accurately weigh 14.0g of EUDRAGITE100 (pressure-sensitive adhesive) and 0.7g of adipic acid, add 50ml of nisoldipine alcohol body fluid, stir until the pressure-sensitive adhesive is completely swollen, then add 2.0ml of azone, 1.0g of menthol, citrate Triethyl citrate 2.0ml and glycer...

Embodiment 2

[0042] The nisoldipine elastosome controlled-release patch is composed of a backing layer, a skeleton drug-containing reservoir layer and an anti-adhesive layer, and its preparation method is as follows:

[0043] (1) Accurately weigh 0.4g of nisoldipine, 2.0g of phospholipids and 0.4g of cholesterol, add 40ml of absolute ethanol and stir until they are completely dissolved. Under the condition of rapid stirring, slowly drip into the phosphate buffer (pH 5 .0) in 60ml, to obtain the alcoholic body crude product, which was homogeneously dispersed for 10 min, and then filtered through a 0.22 μm microporous membrane to obtain the nisoldipine alcoholic body fluid with uniform particle size.

[0044] (2) Precisely weigh 6.0g of EUDRAGITEPO (pressure-sensitive adhesive), 7.0g of EUDRAGITRLPO (pressure-sensitive adhesive) and 0.6g of adipic acid, add 50ml of nisoldipine ethanol body fluid, stir until the pressure-sensitive adhesive is completely swollen, and then add azone 1.0ml, euca...

Embodiment 3

[0046] The nisoldipine elastosome controlled-release patch is composed of a backing layer, a skeleton drug-containing reservoir layer and an anti-adhesive layer, and its preparation method is as follows:

[0047] (1) Accurately weigh 0.4g of nisoldipine, 4.0g of phospholipids and 0.45g of cholesterol, add 45ml of absolute ethanol and stir until completely dissolved, under rapid stirring conditions, slowly drop into an aqueous solution containing 0.2% glacial acetic acid kept at 30°C In 55ml, the crude ethosome was obtained, ultrasonically dispersed for 30min, and then filtered through a 0.22 μm microporous membrane to obtain nisoldipine ethanol body fluid with uniform particle size.

[0048] (2) Accurately weigh 7.0g of EUDRAGITS100 (pressure-sensitive adhesive), 6.0g of EUDRAGITL100 (pressure-sensitive adhesive) and 0.8g of succinic acid, add 50ml of nisoldipine alcohol body fluid, stir until the pressure-sensitive adhesive is completely swollen, and then add nitrogen Ketone ...

technical field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and relates to a transdermal drug delivery preparation for treating cardiovascular diseases, in particular to a nisoldipine ethosome controlled-release patch and a preparation method thereof. Background technique

[0002] Nisoldipine (nisoldipine) is a new type of dihydropyridine calcium channel blocker. Its chemical structure is similar to that of nifedipine. The carboxylate methyl group at the 3 or 5 position of nifedipine is replaced by carboxy isobutyl, and its fat solubility is enhanced. , the pharmacological effect is 4 to 10 times that of the latter, and it is one of the strongest calcium antagonists known so far. Its main pharmacological action is to inhibit Ca 2+ Enter the excitatory cells, selectively cause the expansion of peripheral blood vessels and coronary vessels, but have no effect on myocardial contractility and cardiac conduction system. Nisoldipine can al...

Examples

Embodiment 1

[0038] The nisoldipine elastosome controlled-release patch is composed of a backing layer, a skeleton drug-containing reservoir layer and an anti-adhesive layer, and its preparation method is as follows:

[0039] (1) Accurately weigh 0.4g of nisoldipine, 3.0g of phospholipids and 0.3g of cholesterol, add 45ml of absolute ethanol and stir until completely dissolved, under rapid stirring conditions, slowly drop into an aqueous solution containing 0.2% glacial acetic acid kept at 30°C In 55ml, the crude ethosome was obtained, ultrasonically dispersed for 30min, and then filtered through a 0.22 μm microporous membrane to obtain nisoldipine ethanol body fluid with uniform particle size.

[0040] (2) Accurately weigh 14.0g of EUDRAGITE100 (pressure-sensitive adhesive) and 0.7g of adipic acid, add 50ml of nisoldipine alcohol body fluid, stir until the pressure-sensitive adhesive is completely swollen, then add 2.0ml of azone, 1.0g of menthol, citrate Triethyl citrate 2.0ml and glycer...

Embodiment 2

[0042] The nisoldipine elastosome controlled-release patch is composed of a backing layer, a skeleton drug-containing reservoir layer and an anti-adhesive layer, and its preparation method is as follows:

[0043] (1) Accurately weigh 0.4g of nisoldipine, 2.0g of phospholipids and 0.4g of cholesterol, add 40ml of absolute ethanol and stir until they are completely dissolved. Under the condition of rapid stirring, slowly drip into the phosphate buffer (pH 5 .0) in 60ml, to obtain the alcoholic body crude product, which was homogeneously dispersed for 10 min, and then filtered through a 0.22 μm microporous membrane to obtain the nisoldipine alcoholic body fluid with uniform particle size.

[0044] (2) Precisely weigh 6.0g of EUDRAGITEPO (pressure-sensitive adhesive), 7.0g of EUDRAGITRLPO (pressure-sensitive adhesive) and 0.6g of adipic acid, add 50ml of nisoldipine ethanol body fluid, stir until the pressure-sensitive adhesive is completely swollen, and then add azone 1.0ml, euca...

Embodiment 3

[0046] The nisoldipine elastosome controlled-release patch is composed of a backing layer, a skeleton drug-containing reservoir layer and an anti-adhesive layer, and its preparation method is as follows:

[0047] (1) Accurately weigh 0.4g of nisoldipine, 4.0g of phospholipids and 0.45g of cholesterol, add 45ml of absolute ethanol and stir until completely dissolved, under rapid stirring conditions, slowly drop into an aqueous solution containing 0.2% glacial acetic acid kept at 30°C In 55ml, the crude ethosome was obtained, ultrasonically dispersed for 30min, and then filtered through a 0.22 μm microporous membrane to obtain nisoldipine ethanol body fluid with uniform particle size.

[0048] (2) Accurately weigh 7.0g of EUDRAGITS100 (pressure-sensitive adhesive), 6.0g of EUDRAGITL100 (pressure-sensitive adhesive) and 0.8g of succinic acid, add 50ml of nisoldipine alcohol body fluid, stir until the pressure-sensitive adhesive is completely swollen, and then add nitrogen Ketone ...

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