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Method for preparing aprepitant solid dispersing composition

A technology of solid dispersion and aprepitant, which is applied in the direction of drug combination, pharmaceutical formulation, drug delivery, etc., can solve the problems of solubility and dissolution rate reduction, and achieve the effect of improving dissolution characteristics and significant physical stability

Active Publication Date: 2015-01-21
CHIA TAI TIANQING PHARMA GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

During storage, phase separation, crystal growth, or transformation of the amorphous (metastable) to crystalline state inevitably lead to a decrease in solubility and dissolution rate

Method used

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  • Method for preparing aprepitant solid dispersing composition
  • Method for preparing aprepitant solid dispersing composition
  • Method for preparing aprepitant solid dispersing composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Embodiment 1: the preparation of aprepitant raw material

[0049] With reference to the method of Example 75 of Chinese invention patent application CN1142819A, crystalline aprepitant is prepared, and it has the following properties as determined by X-ray diffraction: figure 1 The XRD pattern shown, the measurement conditions are: Cu (40kV, 40mA), 3.0°~45.0°(2θ) scanning, the typical X-ray diffraction peaks are as follows:

[0050]

[0051] It also has figure 2 DSC spectrum shown.

Embodiment 2

[0053] Take 48 grams of aprepitant prepared in Example 1 and pass through a 100-mesh sieve for later use, and copovidone (Copovidone, N-vinylpyrrolidone / vinyl acetate copolymer) VA64 pass through a 60-mesh sieve for later use. Divide aprepitant equally into 3 parts, 12 grams each, and mix them with copovidone VA64 at a mass ratio of 1:5, 1:1 and 1:0.5, and then divide the powder mixture into equal parts each containing There are 12 parts of a mixture of 4 grams of aprepitant, and the mixtures containing different mass ratios are heated at 100°C, 150°C, 200°C, and 250°C to prepare solid dispersion compositions. The specific operation is to feed the powder mixture into a twin-screw extruder, pulverize, mix, and melt in the extruder, extrude a strip-shaped translucent melt, and place the extrudate in a tray to cool and solidify at room temperature. Grinding and passing through a 60-mesh sieve to obtain a solid dispersion composition powder, and measuring its stability and dissolu...

Embodiment 3

[0063] The aprepitant of 4 grams of embodiment 1 is mixed with 4 grams of copovidone (Copovidone, N-vinylpyrrolidone / vinyl acetate copolymer) VA64 respectively after passing through 100 mesh and 60 mesh sieves, then this powder mixture is fed into In the twin-screw extruder, pulverize, mix and melt in the extruder, extrude a strip-shaped translucent melt, put the extrudate in a pan, cool and solidify at room temperature, pulverize and grind through a 60-mesh sieve to obtain a solid dispersion composition powder, its XRD pattern is as attached image 3 As shown, the measurement conditions are: Cu (40kV, 40mA), 3.0°~45.0°(2θ) scanning, the typical X-ray diffraction peaks are as follows:

[0064]

[0065] It also has Figure 4 DSC spectrum shown.

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Abstract

The invention belongs to the field of medicament preparations, and in particular provides a method for preparing an aprepitant solid dispersing composition. The composition contains aprepitant and at least one water-soluble polymer. The method comprises the following steps of: crushing, mixing, melting and extruding the aprepitant and the water-soluble polymer in an extruder, wherein the heating temperature of the extruder is not below the Tg value of the water-soluble polymer or between 30 DEG C below the melting point and the melting point of the aprepitant; and cooling and curing the extruded product, and thus obtaining the solid dispersing composition. The aprepitant solid dispersing composition prepared by the method is dissolved in a water-based medium on an unexpected high level in relatively short time, and has improved dissolving characteristic and remarkable physical stability.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and specifically the invention provides a method for preparing aprepitant solid dispersion composition. Background technique [0002] Aprepitant (Aprepitant) is an NK1 receptor antagonist developed and marketed by Merck. It was approved by the FDA in 2003 as an oral capsule and was listed in the United States for the prevention of postoperative nausea and vomiting, or with other antiemetics. Combined to prevent nausea and vomiting caused by chemotherapy drugs. Compound aprepitant was disclosed for the first time in WO9516679, and its chemical name is 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3 -(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazole)methyl)-morpholine, the structure is shown in formula I . Aprepitant is almost insoluble in water. At pH 2-10, the solubility of aprepitant in water is as low as 3-7 μg / ml, and the Log P at pH 7.0 is 4.8. [0003] [0004] Fo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/00A61K31/5377A61K47/32A61K47/34A61P1/08
Inventor 周文亮张来芳方晓志
Owner CHIA TAI TIANQING PHARMA GRP CO LTD