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Stable cabazitaxel particle redispersible system

A cabazitaxel and redispersion technology, which is used in medical preparations with inactive ingredients, inactive macromolecular compounds, antitumor drugs, etc., can solve the problems of unstable emulsion, reducing interfacial tension, and volatile ethanol, etc. To achieve the effect of convenient transportation and storage, improved stability and good stability

Inactive Publication Date: 2017-04-26
SHENZHEN NEPTUNUS PHARMA RES INST CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The stability problem is the biggest obstacle in its production and preparation process, and it is also the main reason for its few varieties on the market. The reasons for the instability of the emulsion mainly include the following aspects: First, the preparation must be autoclaved before being packaged and stored. The temperature often exceeds the cloud point of the surfactant, making the emulsion turbid or even broken, resulting in drug precipitation; second, the ratio of each phase is often changed when the emulsion is diluted, and the original nanoemulsion area is destroyed.
Therefore, after oral or intravenous injection, when the emulsion is rapidly diluted by a large amount of gastric juice and blood, it may cause phase transition and particle size increase, which will affect its stability; the third is to prepare nanoemulsion with ethanol as a co-emulsifier, Ethanol is easy to volatilize during long-term storage, which may lead to insufficient co-emulsifiers to further reduce the interfacial tension and increase the fluidity of the interface, making it difficult to maintain the interfacial film formed by the emulsifier and co-emulsifier, which may eventually affect the nanoemulsion stability
The common fat emulsion formula is not suitable for making freeze-dried products, and the ordinary freeze-drying process cannot effectively guarantee the stability and integrity of the emulsion during the freeze-drying process

Method used

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  • Stable cabazitaxel particle redispersible system
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  • Stable cabazitaxel particle redispersible system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Embodiment 1 Cabazitaxel particle redispersible system

[0030] Component ratio (mg):

[0031]

[0032] Preparation:

[0033] (1) Cabazitaxel, phospholipids and citric acid are dissolved in an appropriate amount of chloroform / dichloromethane as the oil phase;

[0034] (2) dissolving bovine albumin, phospholipids and mannitol in an appropriate amount of deionized water as the water phase;

[0035] (3) Add the oil phase prepared in (1) dropwise to (2), grind it with equipment such as grinding or high-pressure homogenization, take it out, fill it, and obtain cabazitaxel particles after step-by-step freeze-drying redispersible system. The particle size was measured with a laser particle size analyzer, and the result was 301 nm, and the result after redispersion was 364 nm.

Embodiment 2

[0036] Example 2 Multiphase stable albumin-bound cabazitaxel

[0037] Component ratio (mg):

[0038]

[0039] Preparation:

[0040] (1) Cabazitaxel, PEG-PLGA and citric acid are dissolved in an appropriate amount of chloroform / dichloromethane as the oil phase;

[0041] (2) dissolving the prescribed amount of albumin, PEG-PLGA, and mannitol in an appropriate amount of deionized water as the water phase;

[0042] (3) Add the oil phase prepared in (1) dropwise to (2), grind it with equipment such as grinding or high-pressure homogenization, take it out, fill it, and obtain cabazitaxel particles after step-by-step freeze-drying redispersible system. The particle size was measured with a laser particle size analyzer, and the result was 336 nm, and the result after redispersion was 386 nm.

Embodiment 3

[0043] Example 3 Multiphase stable albumin-bound cabazitaxel

[0044] Component ratio (mg):

[0045]

[0046] Preparation:

[0047] (1) Dissolving cabazitaxel, PEG-PLGA and citric acid in an appropriate amount of chloroform / dichloromethane as the oil phase;

[0048] (2) Dissolving prescription amount phospholipids, PEG-PLGA and mannitol in an appropriate amount of deionized water as the water phase;

[0049] (3) Add the oil phase prepared in (1) dropwise to (2), grind it with equipment such as grinding or high-pressure homogenization, take it out, fill it, and obtain cabazitaxel particles after step-by-step freeze-drying. redispersion system. The particle size was measured with a laser particle size analyzer, and the result was 223 nm, and the result after redispersion was 267 nm. Example 4 Multiphase stable albumin-bound cabazitaxel

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Abstract

The invention belongs to the field of pharmaceutical preparations, and relates to a good-stability particle solution redispersible system with oil in water as a carrier, and the preparation comprises cabazitaxel, a carrier material, a stabilizer, a protective agent and a pH regulator. The preparation can solve the stability problem, in the preparation process, key parameters are an appropriate emulsion formula, an appropriate cryoprotector and a unique freeze-drying curve, and an injection dry emulsion agent with relatively stable physicochemical properties can be obtained by solving of the three main problems. The preparation provides a feasible method for solving the stability of a nanoemulsion agent.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a formulation of a stable redispersible system of cabazitaxel microparticles and a preparation method thereof. Background technique [0002] Cabazitaxel is a new member of the taxane family. Its anti-cancer mechanism and characteristics are similar to those of docetaxel, and it belongs to anti-microtubule drugs. Cabazitaxel binds to tubulin, promotes its assembly into microtubules, and at the same time prevents the disassembly of these assembled microtubules, stabilizes the microtubules, and then inhibits cell mitosis and interphase cell function. Compared with other paclitaxel drugs on the market, the drug has a lower affinity with the drug-expelling pump mediated by P-glycoprotein, and the probability of drug resistance is lower, so it can be used to treat multidrug-resistant tumors. This drug crosses the blood-brain barrier. In combination with prednisone or predniso...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K47/42A61K47/24A61K47/34A61K47/10A61K47/12A61K47/26A61K31/337A61P35/00
CPCA61K9/1075A61K9/0019A61K31/337A61K47/10A61K47/12A61K47/24A61K47/26A61K47/34A61K47/42
Inventor 田野王志国王丽丽崔婧肖琰杨经安
Owner SHENZHEN NEPTUNUS PHARMA RES INST CO LTD