Preparation method of everolimus solid dispersion

A solid dispersion, everolimus technology, applied in antitumor drugs, powder delivery, drug combination and other directions, can solve the problems of difficult material handling, low drying efficiency, etc., to improve drying efficiency, avoid oxidative degradation, and surface crispy Effect

Inactive Publication Date: 2017-01-04
CHANGZHOU LANLING PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The purpose of the present invention is to solve the problems in the prior art that the air direct contact type is easy to cause the oxidative degradation of everolimus and the air non-direct contact type has low drying efficiency and difficult material handling, and provides a method that can effectively avoid everolimus Preparation method of everolimus solid dispersion with high drying efficiency and simple material handling after drying

Method used

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  • Preparation method of everolimus solid dispersion
  • Preparation method of everolimus solid dispersion

Examples

Experimental program
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Effect test

Embodiment 1）

[0025] The preparation method of the everolimus solid dispersion of the present embodiment has the following steps:

[0026] ① Mix 1 g of everolimus, 8.98 g of hydroxypropyl methylcellulose (E3 PREMIUM LV1 from Dow) and 0.02 g of 2,6-di-tert-butyl-4-methylphenol and add to 100 mL of ethanol and 100 mL of acetone, and stir to mix the materials evenly.

[0027] ② Spread the material obtained in step ① evenly on the flat rotating sample tray of the microwave vacuum dryer, turn on the vacuum pump, control the vacuum degree to be ≤-0.085MPa, pre-equilibrate for 2 minutes, set the microwave power to 518W, turn on the microwave function, and wait for the material After the temperature rose to 40°C, microwave vacuum drying was completed.

[0028] Discharge, and then lay the material flat in a vacuum drying oven at 50°C and a vacuum degree of ≤-0.085MPa, and continue to remove the organic solvent for 24h.

[0029] Discharge and pulverize to obtain solid dispersion powder.

Embodiment 2）

[0031] The preparation method of the everolimus solid dispersion of the present embodiment has the following steps:

[0032] ①Mix 10g of everolimus and 30g of hydroxypropyl methylcellulose (E3 PHARM from Ashland), add 1000mL of ethanol, and stir to mix the materials evenly.

[0033] ② Spread the material obtained in step ① evenly in the sample tray of the three-dimensional rotating support of the microwave vacuum dryer, turn on the vacuum pump, control the vacuum degree to be ≤-0.090MPa, pre-equilibrate for 10 minutes, set the microwave power to 550W, turn on the microwave function, wait for After the temperature of the material rose to 50°C, microwave vacuum drying was completed.

[0034] Discharge and pulverize to obtain solid dispersion powder.

Embodiment 3）

[0036] The preparation method of the everolimus solid dispersion of the present embodiment has the following steps:

[0037] ① Mix 1 g of everolimus, 20 g of hydroxypropyl methylcellulose (630 from Shin-Etsu), 3.9 g of lactose monohydrate and 0.1 g of dl-α-tocopherol acetate, then add 300 mL of methanol and 200 mL of methanol of acetone, and stir to mix the materials evenly.

[0038] ② The material obtained in step ① is evenly spread on the material belt of the belt-type continuous production microwave vacuum continuous dryer through the feeding device, and the vacuum degree is controlled to be ≤-0.080MPa, and the conveying speed and microwave power are adjusted. The material device collects the material.

[0039] Discharge and pulverize to obtain solid dispersion powder.

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Abstract

The invention discloses a preparation method of everolimus solid dispersion. The preparation method particularly comprises the following steps that 1, everolimus, hydroxypropyl methyl cellulose and organic solvent are stirred and mixed to be uniform; 2, the organic solvent in the materials which are stirred to be uniform in the step 1 is removed through a microwave vacuum drying method, and then the everolimus solid dispersion is obtained, wherein the vacuum degree of microwave vacuum drying is lower than or equal to 0.080 MPa, and the drying temperature is lower than or equal to 55 DEG C. According to the method, the organic solvent in the preparation process of the everolimus solid dispersion is removed by adopting the microwave vacuum drying method which is conventionally applied to agricultural product and food processing, oxidative degradation of everolimus can be effectively avoided, the drying efficiency can be greatly improved, the dried materials are loose in surface, and the next processing step is easy to operate.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a preparation method of everolimus solid dispersion. Background technique [0002] Everolimus is an oral and effective rapamycin derivative developed by Novartis, which belongs to a new generation of macrolide immunosuppressive and antitumor drugs. [0003] Everolimus is a poorly soluble and low-stability drug, and its solubility in water, 0.1 mol / L hydrochloric acid solution, and buffer solutions with different pH (pH=2.0-10.0) are all less than 0.1 mg / mL. In addition, everolimus is a heat-sensitive drug, which is prone to oxidative degradation in contact with air at high temperature, and usually needs to be stored at -20°C protected from light under the protection of antioxidants. [0004] In order to improve the dissolution rate of the drug and increase the oral bioavailability, one of the methods commonly used in the field is to use the solven...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K31/436A61K47/38A61P37/06A61P35/00
CPCA61K31/436A61K9/146
Inventor 柴旭煜刘玉华陈中亚尹文娟李金樊榕
Owner CHANGZHOU LANLING PHARMA
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