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Apremilast oral liquid and preparation method thereof

An oral liquid and solution technology, which is applied in the directions of pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., can solve the problems of poor water solubility, slow dissolution, hindering the development of effective pharmaceutical compositions, etc. Ease of dosing, increased water solubility, and improved bioavailability

Active Publication Date: 2016-09-07
LIANGJIANG MEDICINE CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] But apremilast is practically insoluble in water, thus greatly hampering the development of its effective pharmaceutical composition
At present, the preparation of Apremilast is in the form of tablets. Although the dose is gradually increased from 10mg, 20mg to 30mg, due to poor water solubility, the dissolution is slow after oral administration, and the drug absorption is still not ideal.

Method used

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  • Apremilast oral liquid and preparation method thereof
  • Apremilast oral liquid and preparation method thereof
  • Apremilast oral liquid and preparation method thereof

Examples

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preparation example Construction

[0038] The present invention also provides a preparation method of Apremilast oral liquid, comprising:

[0039] A) dissolving Apremilast and a surfactant in an alcoholic solvent to obtain a premilil solution;

[0040] B) stirring and dissolving sulfobutyl-β-cyclodextrin in hot water to obtain a sulfobutyl-β-cyclodextrin solution;

[0041] C) the solution obtained in step A) and the solution obtained in step B) are mixed and dispersed under high shear to obtain Apremilast oral liquid;

[0042] The mass ratio of said Apremilast, surfactant, alcohol solvent and sulfobutyl-β-cyclodextrin is (0.05~0.3):(0~2):(1~30):(0.5~20 ).

[0043] The temperature of the hot water is preferably 50°C±5°C.

[0044] The steps B), C) are not in order.

[0045] Preferably in the present invention, said step C) after high-shear dispersion, also includes:

[0046] Dissolve methylparaben and propylparaben in pure water and boil, and mix with the high-shear dispersion system.

[0047] Preferably, a...

Embodiment 1

[0050] Oral solution prescription composition:

[0051]

[0052]

[0053] Preparation Process:

[0054] Mix Apremilast raw material with polyethylene glycol (PEG) evenly, ultrasonicate for 5 minutes, and set aside. Another sulfobutyl-β-cyclodextrin was dissolved in about 600ml of purified water, heated to 50°C±5°C, and kept warm. Slowly add the previously configured apremilast mixture to the solution, and simultaneously use a high-shear emulsifier (3000 rpm) to disperse and dissolve for 4 hours. After filtration, a transparent aqueous solution of apremilast clathrate was obtained.

[0055] Heat and dissolve methyl p-hydroxybenzoate and propyl p-hydroxybenzoate with a small amount of purified water and boil for 30 minutes, then add to the above solution. Then add sucralose and pineapple essence, and stir to dissolve. Add water to 1000ml, stir, take a sample after the liquid medicine is uniform, filter it after passing the test, and pack it separately.

Embodiment 2

[0057] Oral solution prescription composition:

[0058] prescription

content

Apremilast API (g)

1.0

Sulfobutyl-β-cyclodextrin (g)

30

Propylene glycol (ml)

100

Tween-80(g)

5

Sodium saccharin (g)

4

Vanilla essence (g)

0.5

Methylparaben (g)

1.5

Propylparaben (g)

0.23

Purified water (ml)

1000

[0059] Preparation Process:

[0060] Mix Apremilast with alcoholic co-solvent and surfactant evenly, ultrasonicate for 5min, and set aside. All the other processes are the same as in Example 1.

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Abstract

The invention provides an Apremilast oral liquid, including 0.05wt%-0.3wt% of Apremilast, 0.5wt%-20wt% of sulfobutyl- beta-cyclodextrin, 1wt%-30wt% of an alcohol solvent, 0-2wt% of surface active agent and the balance of water. The invention adopts sulfobutyl- beta-cyclodextrin for Apremilast inclusion, so that Apremilast is in an amorphous state, and has increased water solubility, and the concentration of Apremilast is increased to more than 1mg / ml. The prepared oral liquid is easy for the dosing, and has greatly improved bioavailability due to no disintegration and dissolution process of solid preparations. At the same time, and the stability of Apremilast is not affected due to production into oral liquid; and test shows that the stability of the oral liquid is equal to that of tablets.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a premilast oral liquid and a preparation method thereof. Background technique [0002] Apremilast is a new oral selective phosphodiesterase-4 (PDE4) inhibitor developed by Celgene, which was first approved by the FDA for the treatment of psoriatic arthritis on March 21, 2014. On March 23, a new indication was added for the treatment of patients with moderate to severe plaque psoriasis who are suitable for phototherapy and systemic therapy. Apremilast selectively inhibits PDE4, prevents rheumatoid synoviocytes from secreting tumor necrosis factor α (TNF-α) and produces anti-inflammatory activity, which can reduce joint swelling and improve the physiological functions of joints. PDE4 has been a potent anti-inflammatory molecular target for at least 30 years, but apremilast is the first and only PDE4 inhibitor approved by the FDA for the treatment of psoriatic ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/08A61K31/4035A61K47/48A61P17/06A61P19/02
CPCA61K9/0053A61K9/08A61K31/4035A61K47/14A61K47/26
Inventor 王森弘余灏贺耘
Owner LIANGJIANG MEDICINE CO LTD
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