Everolimus oral membrane agent and preparation method thereof

An oral film, everolimus technology, applied in the field of medicine, can solve the problems of large individual differences and low bioavailability of everolimus, achieve the effects of light weight, avoid first-pass effect, and improve preparation stability

Active Publication Date: 2020-07-10
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Everolimus is a substrate of CYP3A4 and PgP, resulting in the disadvantages of low bioavailability and large individual differences of everolimus

Method used

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  • Everolimus oral membrane agent and preparation method thereof
  • Everolimus oral membrane agent and preparation method thereof
  • Everolimus oral membrane agent and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Prescription: Everolimus: 20mg

[0068] HPMCE5: 240mg

[0069] PEG400: 144mg

[0070] Gum Arabic: 96mg

[0071] Preparation:

[0072] Disperse HPMCE5 in 4ml of 75% ethanol and stir in a 60°C water bath until dissolved;

[0073] While stirring, add a small amount of gum arabic to the HPMCE5 aqueous solution several times, and stir in a 60°C water bath until it dissolves;

[0074] Add the solution obtained in step (2) into PEG400, stir and mix well.

[0075] After the solution obtained in step (3) was cooled to room temperature, everolimus was added, and stirred for 10 minutes to mix well.

[0076] The solution obtained in step (4) is left to defoam. Cast the formed non-bubble viscous liquid on a mold, dry it in vacuum at 50°C for 12 hours, take out the film, cut it into 2×2cm size, and get it.

Embodiment 2

[0078] Prescription: Everolimus: 20mg

[0079] HPMCE5: 240mg

[0080] Glycerin: 96mg

[0081] Gum Arabic: 96mg

[0082] Preparation:

[0083] Disperse HPMCE5 in 4ml of 75% ethanol and stir in a 60°C water bath until dissolved;

[0084] While stirring, add a small amount of gum arabic to the HPMCE5 aqueous solution several times, and stir in a 60°C water bath until it dissolves;

[0085] Add the solution obtained in step (2) into glycerin, stir and mix well.

[0086] After the solution obtained in step (3) was cooled to room temperature, everolimus was added, and stirred for 10 minutes to mix well.

[0087] The solution obtained in step (4) is left to defoam. Cast the formed viscous suspension without bubbles on a mold, dry it in vacuum at 50°C for 12 hours, take out the film, cut it into 2×2cm size, and get it.

Embodiment 3

[0089] Prescription: Everolimus: 20mg

[0090] Methylcellulose (MC): 144mg

[0091] Glycerin: 48mg

[0092] Gum Arabic: 96mg

[0093] Preparation:

[0094] Weigh the prescribed amount of methylcellulose, glycerin, and gum arabic, and disperse them in 1ml of purified water, heat in a water bath at 60°C, stir until dissolved, and cool to room temperature when the solution is clear.

[0095] Weigh the prescribed amount of everolimus and dissolve it in 3ml of absolute ethanol, stir until dissolved.

[0096] Add the liquid medicine obtained in step (2) into the solution obtained in step (1) under constant stirring, and stir for 30 minutes to mix well.

[0097] The solution obtained in step (3) is left to defoam. Cast the formed viscous liquid without bubbles on the mold, dry it in vacuum at 50°C for 12 hours, take out the film, cut it into the required size, and get it.

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Abstract

The invention relates to the technical field of medicines, in particular to an everolimus oral membrane agent and a preparation method thereof. The everolimus oral membrane agent comprises the following ingredients in a membrane forming solution according to the content as follows: 0.5-2.5 g / 100 ml of everolimus, 2.4-6 g / 100 ml of membrane forming materials, 1.2-4.8 g / 100 ml of plasticizer and1-5 g / 100 ml of stabilizing agents. In the everolimus oral membrane agent, the introduction of Arabic gum effectively delays the oxidization of the everolimus, and the stability of the preparation isimproved. A dosage form can be put under the tongue to be quickly dissolved to enter the human body to be circulated, enzymatic degradation in gastrointestinal tracts is avoided, and bioavailabilityis obviously improved. The dosage form does not need to be swallowed, and the medicine utilization compliance and safety of old people and infant patients are especially improved.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to an everolimus oral film and a preparation method thereof. Background technique [0002] Everolimus (RAD-001), a mTOR inhibitor first developed by Novartis, is a 40-O-(2-hydroxyethyl) derivative of rapamycin . Everolimus has poor chemical stability and is sensitive to humidity, heat and light, and is prone to degradation especially under high humidity conditions. Soluble in methanol and 99.5% ethanol (>10g / 100ml), almost insoluble in 0.1mol / L hydrochloric acid, pH2.0-10.0 citrate buffer, water, 0.9% sodium chloride solution (<0.01g / 1 100ml). Everolimus is a substrate of CYP3A4 and PgP, resulting in the disadvantages of low bioavailability and large individual differences of everolimus. [0003] As an mTOR inhibitor, everolimus can bind to FK506 binding protein-12 (FKBP-12) in cells to form an inhibitory complex mTORC1, thereby inhibiting the activation of mTOR kinase. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/70A61K31/436A61K47/38A61K47/36A61K47/10A61P35/00
CPCA61K9/006A61K31/436A61K47/38A61K47/36A61K47/10A61P35/00A61K9/7007
Inventor 刘洪卓马艺荻杨杨
Owner SHENYANG PHARMA UNIVERSITY
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