15 results about "Vortioxetine Hydrobromide" patented technology

The invention particularly relates to a preparation method of a high-fluidity vortioxetine hydrobromide alpha crystal form. According to the technical scheme, vortioxetine hydrobromide is dissolved in an organic solvent with the volume being 5-10 times that of the vortioxetine hydrobromide, insoluble substances are filtered out, and polyvinylpyrrolidone with the mass being 1-2.5 times that of the vortioxetine hydrobromide is added into filtrate; and feeding the solution into pre-cooled purified water containing seed crystals for crystallization, filtering, and drying to constant weight. The obtained vortioxetine hydrobromide is in an alpha crystal form, is spherical, has the particle size of less than 15 microns and the specific surface area of more than 1600 m < 2 > / kg, and is high in dissolution rate, good in fluidity, high in yield and easy to industrialize.

The invention discloses a method for detecting an N-nitroso compound in vortioxetine hydrobromide, and the N-nitroso compound is 2, 2 '-(nitroso amino) bis-acetonitrile. According to the method, a high performance liquid chromatography is adopted, an octadecyl silane bonded silica gel filler chromatographic column and an ultraviolet detector are adopted, a mobile phase A is 0.05% phosphoric acid aqueous solution, a mobile phase B is methanol, and gradient elution is adopted. The method has good specificity and sensitivity.

This application discloses coated granules, solid dispersions, combinations and formulations for oral taste masking, which have been shown to improve the taste masking effect of vortioxetine hydrobromide and increase patient compliance and tolerability.

This application discloses an analytical method for N-nitrosamine vortioxetine in vortioxetine hydrobromide tablets, belonging to the field of pharmaceutical impurity analysis. The method employs high-performance liquid chromatography (HPLC), with the following chromatographic conditions: a 4.6 mm × 250 mm column packed with octadecylsilane-bonded silica gel, with a particle size of 5 μm; mobile phase A is a 90:10 water-acetonitrile mixture containing 0.025%–0.035% trifluoroacetic acid (v / v); mobile phase B is acetonitrile; gradient elution; column temperature 38–42 °C; flow rate 0.9–1.1 ml / min; injection volume 50 μl; and detection wavelength 226 nm. This analytical method effectively eliminates excipient interference and exhibits excellent detection performance (specificity, sensitivity, linearity, precision, accuracy, and robustness), accurately detecting the content of N-nitrosamine vortioxetine in vortioxetine hydrobromide tablets, meeting quality control requirements.

The invention discloses a preparation method of hydrobromic acid vortioxetine, and belongs to the technical field of organic synthesis. The method comprises the following steps: by taking o-aminothiophenol and Boc2O as initial raw materials, carrying out amino protection to obtain an intermediate 1; reacting the intermediate 1 with 2, 4-dimethyl bromobenzene under an alkaline condition to form a thioether bond, and acidifying to obtain an intermediate 2; carrying out high-temperature cyclization on the intermediate 2 and bis (2-bromoethyl) amine hydrobromide in mesitylene, so as to obtain a crude product of the hydrobromic acid vortioxetine; and recrystallizing the crude product with 95% ethanol to obtain a high-purity final product. The route is simple, only three-step reaction is needed, a noble metal catalyst is not needed in the whole process, and the problem of metal residues is fundamentally avoided; the selected raw materials are easy to obtain, the reaction condition is mild, the operation is simple and convenient, the process is stable, the total yield is good, the product purity is as high as 99.9%, and the method is suitable for large-scale production.

The invention provides a method for analyzing impurities in a hydrobromic acid povidone-soluble film, which comprises the following steps: dissolving the hydrobromic acid povidone-soluble film in an acetonitrile-water solution, and uniformly shaking to obtain a test solution; the method comprises the following steps: respectively dissolving a hydrobromic acid vortioxetine reference substance and impurity 18 and 21 reference substances in an acetonitrile-water solution, and uniformly shaking to obtain a reference substance solution; detecting the test solution and the reference solution by adopting a high performance liquid chromatography, wherein the detection adopts gradient elution; wherein the mobile phase A is ammonium acetate solution-water-methanol with the volume ratio of 10: 55: 35, and the mobile phase B is ammonium acetate solution-methanol with the volume ratio of 10: 90. According to the scheme, a high performance liquid chromatography method is adopted, automatic operation can be achieved, the content of all components in a sample can be effectively detected, impurities can be checked at the same time, the elution time is shortened to 30 minutes, and the analysis efficiency is improved.

The application belongs to the technical field of crystal form drug preparation, and particularly relates to a preparation method of high-stability vortioxetine hydrobromide crystal form alpha. Vortioxetine hydrobromide is an antidepressant widely used at present, and the crystal form alpha thereof has higher solubility and better bioavailability, but is unstable and is easy to be transformed into the crystal form beta. The preparation method comprises the following steps: adding vortioxetine hydrobromide into an alcohol-water mixed solution to fully dissolve, applying a direct current electric field to induce the formation of the crystal form alpha, and controlling the cooling rate to crystallize for 1-2 hours, so that the crystal form alpha with high purity and good stability is prepared, and the crystal form alpha will not be transformed for a long time, and has better safety when applied to clinical preparations.

The invention relates to an HPLC detection method for related substances of vortioxetine hydrobromide tablets. The test solution of the HPLC detection method is a methanol solution containing vortioxetine impurities, the mobile phase A is a mixed solution of diammonium hydrogen phosphate buffer and methanol, and the mobile phase B is methanol; the elution procedure is: #imgabs0# The method can detect many impurities and can quickly, effectively and accurately monitor related substances in vortioxetine hydrobromide tablets. The separation between a main peak of vortioxetine hydrobromide and adjacent impurity peaks is greater than 1.5, and the impurities can be effectively separated from the main peak. The method is simple to operate, has good specificity, linearity and precision, and the solution is stable. The quantitative limit and the detection limit are both small, the accuracy is high, and the method is durable.

The invention belongs to the technical field of crystal form medicine preparation, and particularly relates to a preparation method of a high-stability vortioxetine hydrobromide crystal form alpha. The vortioxetine hydrobromide is an antidepressant drug which is widely applied at present, and the crystal form alpha of the vortioxetine hydrobromide is relatively high in solubility and relatively good in bioavailability, but the vortioxetine hydrobromide is unstable and is easily transformed into a crystal form beta. The preparation method comprises the following steps: adding vortioxetine hydrobromide into an alcohol-water mixed solution for fully dissolving, applying a direct-current electric field to induce the formation of the crystal form alpha, and controlling the cooling rate to grow the crystal for 1-2 hours, so that the crystal form alpha with high purity and good stability is prepared, does not generate crystal transformation after being placed for a long time, and has better safety when being applied to a clinical preparation.

The application relates to a preparation method of a high-fluidity alpha crystal form of vortioxetine hydrobromide. The technical scheme of the application is that vortioxetine hydrobromide is dissolved in 5-10 times the volume of an organic solvent, and after the insoluble substances are filtered out, 1-2.5 times the mass of polyvinylpyrrolidone is added to the filtrate. The above solution is flowed into pre-cooled purified water containing crystal seeds to crystallize, is filtered, and is dried to constant weight to obtain vortioxetine hydrobromide. 2 The vortioxetine hydrobromide obtained by the method is in an alpha crystal form, is spherical in shape, has a particle size less than 15 mu m, a specific surface area higher than 1600 m 2 / g, a fast dissolution rate, good fluidity, high yield, and is easy to realize industrialization.

A coated granule, a solid dispersion, a composition, and a preparation for oral masking, which improve the taste masking effect of vortioxetine hydrobromide, and improve the patient adherence and compliance.

The invention discloses a lyotropic liquid crystal long-acting injection as well as a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. The preparation consists of a raw material medicine, a lipid material, an organic solvent and a release regulator, and hexagonal phase liquid crystal gel can be spontaneously formed after injection so as to realize long-acting slow release. The preparation can be prepared by stirring and mixing at room temperature, and has the advantage of simple and convenient preparation process. Experiments show that the effective blood concentration in the body can be maintained for more than 14 days after single hypodermic injection, the half-life period of the medicine is prolonged to 187 hours from about 66 hours of oral administration, and the burst release phenomenon is avoided. The invention effectively solves the clinical pain points of frequent administration, large blood concentration fluctuation, poor patient compliance and the like of the existing oral preparation of the hydrobromic acid vortioxetine.

This disclosure belongs to the field of biomedical technology, specifically relating to vortioxetine hydrobromide sustained-release microspheres, their formulations, preparation methods, and applications. This disclosure has the following advantages: the preparation method of vortioxetine hydrobromide sustained-release microspheres provided in this disclosure can increase drug loading, improve drug encapsulation efficiency, and significantly reduce excipient usage.

The invention relates to a preparation method of a hydrobromic acid vortioxetine alpha crystal form, which comprises the following steps: mixing hydrobromic acid vortioxetine shown in a formula I with a solvent A to obtain the hydrobromic acid vortioxetine alpha crystal form, wherein the solvent A is selected from at least two of n-butyl alcohol, isopropanol and sec-butyl alcohol. The alpha crystal form product obtained by the preparation method is high in purity, good in yield, appropriate in crystal particle size, good in fluidity, better in stability, simple and convenient in steps, low in cost, environment-friendly and suitable for industrial large-scale production.

The invention discloses a 3D printing technology-based vortioxetine hydrobromide implant as well as a preparation method and application thereof, and relates to the technical field of pharmaceutical preparations, a melt extrusion deposition printing technology is adopted, polylactic acid with excellent biocompatibility is taken as a drug carrier material, vortioxetine hydrobromide is taken as a model drug, and a customized three-dimensional model is constructed, so that the vortioxetine hydrobromide implant is prepared. And the auxiliary material system and the drug loading capacity are subjected to adaptive screening, meanwhile, key 3D printing process parameters such as the filling distance, the layer thickness, the printing needle diameter and the printing path are optimized, and accurate forming of the implant is achieved. The preparation method has the advantages of simplicity and convenience in operation, low energy consumption, short production cycle, controllable process and the like, and the prepared implant has good biocompatibility, can realize long-term (40-80 days) stable release of drugs, and improves the medication compliance of patients.