Apixaban co-micronized product

A technology of co-micronization and apixaban, which is applied in the field of medicine, can solve the problems of poor reproducibility, poor compressibility of excipients, and difficult particle control, so as to improve bioavailability, increase dissolution rate, and good stability Effect

Active Publication Date: 2020-06-02
ZHANGZHOU PIEN TZE HUANG PHARM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the repeated compression and crushing of dry granulation makes the compressibility of excipients worse, which is not conducive to subsequent tablet compression, and the process is more cumbersome
[0011] The publication number is CN102770126, which discloses the technology of dry granulation and wet granulation. The disadvantage of its wet granulation is that

Method used

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  • Apixaban co-micronized product

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0047] Example 1: Screening of excipients for co-micronization of apixaban

[0048] 1. Materials and methods

[0049] The apixaban and the co-micronized excipient to be tested are mixed in a hopper mixer according to the desired weight ratio until a homogeneous mixture is obtained. Subsequently, the obtained mixture is micronized in a jet mill.

[0050] In vitro dissolution of co-micronized apixaban

[0051] For each of the obtained co-micronized products, a tablet containing an amount corresponding to 2.5 mg of apixaban was prepared.

[0052] The dissolution test method adopts the second method in the Chinese Pharmacopoeia 2015 version of the dissolution test method. The 0.05mol / L sodium phosphate solution (the pH value is adjusted to 6.8 with phosphoric acid) is selected as the discriminating dissolution medium, and the paddle method is 75 rpm. The temperature is 37±0.5℃, and it is measured by Lugen dissolution apparatus.

[0053] Sampling time is 5, 10, 15, 20, 30, 45, 60 minutes, ...

Example Embodiment

[0061] Example 2 The effect of apixaban / sodium lauryl sulfate weight ratio on the in vitro dissolution of apixaban

[0062] 1. Materials and methods

[0063] According to the aforementioned co-micronization method, various apixaban / sodium lauryl sulfate co-micronized products were prepared to facilitate the study of the weight ratio of apixaban / sodium lauryl sulfate to the in vitro effects of apixaban The effect of dissolution rate.

[0064] 2. Results

[0065] Table 2 below and figure 2 Shows the dissolution results obtained for each co-micronized product prepared.

[0066] Table 2: The percentage of apixaban released relative to the initial amount of apixaban contained in the tablet

[0067]

[0068] The above results indicate that the dissolution rate of apixaban increases as the weight ratio of apixaban / sodium lauryl sulfate decreases.

Example Embodiment

[0069] Example 3: Apixaban / sodium lauryl sulfate co-micronized product mixed with apixaban / sodium lauryl sulfate Comparison of dissolution characteristics between compounds

[0070] 1. Materials and methods

[0071] Apixaban and sodium lauryl sulfate can be mixed in a mortar at a weight ratio of 3 / 1 and ground until a homogeneous mixture is obtained.

[0072] The remaining mixture is co-micronized by a jet milling micronizer, and the obtained micronized product (that is, each tablet contains 2.5 mg of apixaban) is compressed into tablets.

[0073] The dissolution of apixaban of these two types of tablets was studied under the same conditions and the same dissolution medium as described in Example 1.

[0074] 2. Results

[0075] The dissolution results obtained for apixaban / sodium lauryl sulfate co-micronized product and unmicronized apixaban / sodium lauryl sulfate mixture (physical mixture) are shown in Table 3 below and image 3 Shown in.

[0076] Table 3: The percentage of apixaban rel...

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Abstract

The invention discloses an apixaban co-micronized product and a preparation method thereof and also discloses pharmaceutical composition containing the co-micronized product and a preparation method of the pharmaceutical composition. The pharmaceutical composition containing the apixaban co-micronized product is good in stability, can realize industrialization, is better applied to clinic, has more obvious advantages and can effectively improve the dissolution rate and the bioavailability.

Description

[0001] 1. Technical field [0002] The invention belongs to the technical field of medicine, and in particular relates to a co-micronized product of apixaban, a pharmaceutical composition containing the above-mentioned co-micronized product and a preparation method thereof. [0003] 2. Background technology [0004] Apixaban (Apixaban, trade name Eliquis) is an oral selective activated factor Xa inhibitor. In 2007, BMS teamed up with Pfizer to announce the joint development of apixaban, a new oral anticoagulant owned by BMS, as an upgraded alternative to warfarin. [0005] In 2011, Apixaban was approved for marketing in the European Union; in 2012, it was approved by the FDA; in 2013, it entered China, and in 2017, it entered the new version of the medical insurance catalog, which is used for adult patients undergoing elective hip or knee replacement to prevent venous thrombosis Embolic event. [0006] Apixaban is the third new-generation oral anticoagulant to be marketed aft...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K47/20A61K9/28A61K31/4545A61P7/02
CPCA61K9/145A61K9/2095A61K9/2013A61K9/28A61K31/4545A61P7/02
Inventor 黄进明洪绯于娟陈志亮罗志毅高龙辉纪学慧曹亮
Owner ZHANGZHOU PIEN TZE HUANG PHARM
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