Edoxaban tosylate preparation and preparation method thereof

A technology of edoxaban and toluenesulfonic acid, which can be used in pharmaceutical formulations, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc., can solve the problem of reduced bioavailability, affecting drug absorption, and adverse clinical treatment and other problems, to achieve the effect of improving the dissolution rate and degree of dissolution, low technical difficulty, and reducing the degree of crystallinity

Active Publication Date: 2022-04-29
NKD PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Edoxaban tosylate is a basic compound that exhibits good solubility in acidic aqueous solutions, but decreases in neutral aqueous solutions (such as pH 6.8 buffer)
The poor dissolution rate of edoxaban tosylate in neutral media may also affect the absorption of the drug in the intestine, which will lead to a decrease in bioavailability, which is not conducive to clinical treatment

Method used

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  • Edoxaban tosylate preparation and preparation method thereof
  • Edoxaban tosylate preparation and preparation method thereof
  • Edoxaban tosylate preparation and preparation method thereof

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preparation example Construction

[0033] The present invention also provides a preparation method of edoxaban tosylate preparation, comprising the following steps:

[0034] 1) Weighing 20-30% of edoxaban tosylate and 70-80% of hydrophilic carrier material by mass percentage, adding purified water 1.5-4 times the total weight of raw materials to prepare a suspension;

[0035] 2) Nano-grind the above suspension, the grinding speed is 1500rpm-2400rpm, the grinding temperature is 4°C-40°C, and the grinding is stopped until the volume average particle size of the active ingredient reaches 200-400nm;

[0036] 3) Spray-dry the suspension obtained by grinding, enter the air at 118°C-128°C, control the spray speed, keep the outlet air temperature at 55°C-65°C, and maintain a negative pressure of 300Pa-500Pa, and prepare the volume average particle Diameter 125μm-850μm, BET surface area 0.5-2m 2 / g of loose porous microspherical solid dispersion;

[0037] 4) The solid dispersion is prepared by conventional methods to ...

Embodiment 1

[0040] The preparation of embodiment 1 edoxaban tosylate capsules

[0041] Edoxaban tosylate preparation 1, the solid dispersion contains 10% of edoxaban tosylate and 90% of hydrophilic carrier material (by mass percentage).

[0042]

[0043] The specific preparation method is as follows:

[0044] (1) Add edoxaban tosylate and mannitol into purified water whose total weight is 1.5 times that of raw materials to prepare a suspension.

[0045] (2) Nanogrind the above suspension (the grinding medium is zirconia beads with an average particle diameter of 0.3 mm), set the grinding temperature at 10° C., rotate at 2000 rpm, and grind for 60 minutes to obtain a mixture of raw materials with a volume average particle diameter of 200 nm. Suspension.

[0046] (3) Spray-dry the ground suspension to prepare a loose porous microspherical solid dispersion.

[0047] Set the inlet air temperature to 120°C, the liquid spray speed to 300g / min, the outlet air temperature to 55°C, and maint...

Embodiment 2

[0049] The preparation of embodiment 2 edoxaban tosylate tablets

[0050] Edoxaban tosylate preparation 2, the solid dispersion contains 20% of edoxaban tosylate and 80% of hydrophilic carrier material (by mass percentage).

[0051]

[0052] The specific preparation method is as follows:

[0053] (1) Add edoxaban tosylate and galactose into purified water with 2.5 times the total weight of raw materials to prepare a suspension.

[0054] (2) Nanogrind the above suspension (the grinding medium is zirconia beads with an average particle diameter of 0.3mm), set the grinding temperature at 4°C, the rotation speed at 2400rpm, and the grinding time for 50min to obtain a mixture of raw materials with a volume average particle diameter of 300nm. Suspension.

[0055] (3) Spray drying the ground suspension to prepare a loose porous microspherical solid dispersion;

[0056] Set the inlet air temperature to 118°C, the liquid spray speed to 400g / min, the outlet air temperature to 60°C...

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Abstract

The invention discloses an esdoxaban toluenesulfonate preparation and a preparation method thereof. The eldoxaban tosylate preparation is a solid dispersion prepared from the following raw materials in parts by weight: 10-40 parts of eldoxaban tosylate with the volume average particle size of 200-400 nm and 60-90 parts of a hydrophilic carrier material. The volume average particle size of the solid dispersion is 125-850 [mu] m, and the BET surface area is 0.5-2 m < 2 > / g. The volume average particle size of the active ingredients in the preparation product is below 400nm, so that the crystallinity of the medicine is reduced, and the surface area of the medicine is increased; the solid dispersoid is prepared with a hydrophilic carrier material, and the carrier material is combined with the medicine through a hydrogen bond, so that the dissolution speed reduction caused by the agglomeration of superfine medicine particles is avoided. According to the invention, the dissolution speed and dissolution rate of the product in a neutral solution are improved, so that the bioavailability of the medicine in vivo is improved.

Description

technical field [0001] The invention relates to the field of pharmacy, in particular to an edoxaban tosylate preparation and a preparation method thereof. Background technique [0002] Edoxaban tosylate is a selective factor Xa inhibitor indicated for patients with one or more risk factors (eg, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, previous stroke, or transient cerebral For the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NVAF) with a history of ischemic attack (TIA); for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults, and for the prevention of deep vein thrombosis and Recurrent pulmonary embolism. It has the same efficacy as the traditional anticoagulant warfarin, but with better safety. [0003] Daiichi Sankyo Europe GmbH first developed edoxaban tosylate tablets, which were first launched in Japan in April 2011. In December 2018, Yuanyan Daiichi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/60A61K47/58A61K47/54A61K47/61A61K31/444A61P7/02A61P9/10
CPCA61K47/60A61K47/58A61K47/549A61K47/61A61K31/444A61P7/02A61P9/10
Inventor 陶秀梅刘细建尚丽霞刘美平
Owner NKD PHARMA CO LTD
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