- Phenoxy aromatic acid with cyclopropyl and pharmaceutically acceptable salt thereof as well as preparation method and application thereof
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The invention provides phenoxy aromatic acid with cyclopropyl, a preparation method of the phenoxy aromatic acid, pharmaceutically acceptable salt of the phenoxy aromatic acid with cyclopropyl and a preparation method of the pharmaceutically acceptable salt, and further provides dosage forms of the phenoxy aromatic acid with cyclopropyl and the pharmaceutically acceptable salt of the phenoxy aromatic acid with cyclopropyl. The invention also discloses application of the compound in medicines for treating hyperlipidemia diseases. The compound provided by the invention has a relatively good blood fat reducing drug effect, so that the compound has a very good application prospect.
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- Preparation method of choline fenofibrate
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The invention provides a preparation method of choline fenofibrate. The preparation method comprises the following steps: (1) preparation of a coarse choline fenofibrate product: carrying out hydrolyzing and salt forming reactions in a solvent A by taking fenofibrate and bursine as an initiator to obtain choline fenofibrate, wherein the solvent A is selected from one of methanol, ethanol, propanol, normal butanol, water, a bursine aqueous solution and isopropanol; and (2) refining of the choline fenofibrate: dissolving the coarse choline fenofibrate product prepared in the step (1) in a solvent B, decoloring the mixture with activated carbon, and crystallizing and cooling the mixture to obtain a fine choline fenofibrate product, wherein the solvent B is selected from one of ethanol, methanol, water and isopropanol. The preparation method of choline fenofibrate provided by the invention is mild in reaction condition, simple in preparation process, and is high in reaction yield and the product purity reaches over 99.9%.
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Paragraph 0068; 0069
(2019/03/08)
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- Interesting morphological behavior of organic salt choline fenofibrate: Effect of supersaturation and polymeric impurity
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Crystal habit of drug molecules can have significant influence on the processing and performance of pharmaceutical products. During the development of Trilipix, a pharmaceutical product used for the treatment of mixed dyslipidemia, several crystal habits were observed for the active ingredient choline fenofibrate. The dissolution and performance of the drug product were not impacted by changes in crystal habit of the active ingredient due to high solubility of the drug. However, the formulation process was impacted by variations in crystal habit of the active ingredient, requiring robust control of the crystal habit. The crystal habit was greatly influenced by supersaturation during crystallization from a mixed solvent system comprising methanol and isopropanol. In addition to supersaturation, trace levels of a polymeric impurity in the starting material fenofibrate had a detrimental effect on the crystal habit. This article discusses the effects of these factors on the crystal habit of choline fenofibrate and the design of a crystallization process to deliver the target crystal habit, most suited to the formulation process. The article also provides preliminary mechanistic insights into the crystal habit of this organic salt using an extension of the spiral growth model for morphology prediction of organic molecular crystals. An attempt is made to explain the effect of supersaturation and impurity on the crystal habit of choline fenofibrate using the concepts of stability of surfaces, building units, periodic bond chain theory, and the spiral growth model.
- Bordawekar, Shailendra,Kuvadia, Zubin,Dandekar, Preshit,Mukherjee, Samrat,Doherty, Michael
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p. 3800 - 3812
(2014/08/18)
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- PROCESS FOR THE PREPARATION OF CHOLINE SALT OF FENOFIBRIC ACID AND ITS NOVEL POLYMORPH
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The present invention relates to an improved process for the preparation of choline salt of fenofibric acid corresponding to formula (I). The present invention also provides crystalline polymorphic form of choline salt of fenofibric acid corresponding to formula (I) designated as form A.
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Page/Page column 3
(2011/12/12)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF CHOLINE SALT OF FENOFIBRIC ACID AND ITS NOVEL POLYMORPH
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The present invention relates to an improved process for the preparation of choline salt of fenofibric acid corresponding to formula (I). The present invention also provides crystalline polymorphic form of choline salt of fenofibric acid corresponding to formula (I) designated as form A.
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Page/Page column 7
(2010/08/09)
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- Process for Preparing Quaternary Acid and Ammonium Salts
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A process for preparing a quaternary ammonium salt of a fibric acid, represented by the following reaction scheme: is carried out in a single operation starting from a phenol of formula (I), an α-halogenated ester of formula (II) and a quaternary ammonium hydroxide of formula (III). This process makes it possible economically to prepare a choline salt of fenofibric acid in high purity that can be used directly as the active substance in a pharmaceutical composition intended for human consumption.
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Page/Page column 3
(2008/12/08)
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