7 results about "Esomeprazole Magnesium" patented technology

The invention discloses a method for preparing esomeprazole magnesium trihydrate by crystal transformation, and relates to the technical field of pharmaceutical preparations and crystallization. It includes the following steps of preparing an esomeprazole potassium aqueous solution, preparing a magnesium sulfate heptahydrate aqueous solution, a reactive crystallization process to obtain the esomeprazole magnesium tetrahydrate, and filtering the obtained esomeprazole magnesium tetrahydrate to obtain a sphaerocrystal of esomeprazole magnesium trihydrate. The method for preparing esomeprazole magnesium trihydrate by crystal transformation in the present invention is characterized by using the esomeprazole potassium aqueous solution and the magnesium sulfate aqueous solution for ion exchange to obtain the esomeprazole magnesium tetrahydrate. The whole process takes only about 1 hour, which greatly shortens the reaction time, and the obtained esomeprazole magnesium trihydrate has high purity, large particle size, narrow distribution, small angle of repose and good fluidity.

The invention particularly relates to an escomeprazole magnesium enteric-coated particle and a preparation method thereof. The esomeprazole magnesium enteric-coated particles are particles prepared from a pellet core material by a fluidized bed coating medicine carrying layer, an isolating layer and an enteric-coated layer in sequence, the drug carrying layer is prepared from a laminated suspension, the isolation layer is prepared from an isolation pill suspension, the enteric-coated layer is prepared from an enteric-coated pill solution, and escomeprazole magnesium is enriched in the drug carrying layer. According to the preparation method, an aqueous dispersion membrane control technology is adopted, and a multi-unit esomeprazole magnesium enteric-coated particle administration form is adopted, so that burst release is not easy to occur, and the safety is high. The escomeprazole magnesium enteric-coated particles which are stable in quality, smaller in particle size, free of sand feeling during oral administration and higher in compliance are obtained by combining air jet pulverization with fluidized bed liquid phase lamination and microencapsulation technologies, and are suitable for being taken by children.

The invention discloses a method for determining potential genotoxic impurities in esomeprazole magnesium by HPLC (High Performance Liquid Chromatography), which comprises the following steps: preparing a test solution: taking 30-90mg of esomeprazole magnesium, precisely weighing, putting into a 10mL measuring flask, adding a proper amount of methanol, dissolving a sample by ultrasonic treatment, diluting with methanol to a scale, and uniformly shaking; preparing a reference substance solution: taking a proper amount of 4-methoxy-2, 3, 5-trimethylpyridine nitrogen oxide, precisely weighing, quantifying with methanol, and preparing the reference substance solution containing 14-170ng of 4-methoxy-2, 3, 5-trimethylpyridine nitrogen oxide in each 1mL of solution; respectively carrying out HPLC (High Performance Liquid Chromatography) detection on the reference solution and the test solution, and determining the content of the genotoxic impurity 4-methoxy-2, 3, 5-trimethylpyridine nitrogen oxide in the esomeprazole magnesium by adopting an external standard method. The method has the advantages of high separation efficiency, high analysis speed, high detection sensitivity and low detection cost.

The invention discloses a method for preparing esomeprazole magnesium trihydrate by crystal transformation, and relates to the technical field of pharmaceutical preparations and crystallization. It includes the following steps of preparing an esomeprazole potassium aqueous solution, preparing a magnesium sulfate heptahydrate aqueous solution, a reactive crystallization process to obtain the esomeprazole magnesium tetrahydrate, and filtering the obtained esomeprazole magnesium tetrahydrate to obtain a sphaerocrystal of esomeprazole magnesium trihydrate. The method for preparing esomeprazole magnesium trihydrate by crystal transformation in the present invention is characterized by using the esomeprazole potassium aqueous solution and the magnesium sulfate aqueous solution for ion exchange to obtain the esomeprazole magnesium tetrahydrate. The whole process takes only about 1 hour, which greatly shortens the reaction time, and the obtained esomeprazole magnesium trihydrate has high purity, large particle size, narrow distribution, small angle of repose and good fluidity.

The invention discloses a method for preparing esomeprazole magnesium degradation impurities, comprising: oxidizing 3,5-dimethyl-2-hydroxymethyl-4-pyridone to obtain 3,5-dimethyl-2-carboxyl-4-pyridone; in the presence of an inorganic base, condensing 3,5-dimethyl-2-carboxyl-4-pyridone and 2-chloro-5-methoxybenzimidazole; adjusting the pH of the reaction solution to 6-7; filtering; drying the wet product to obtain a crude esomeprazole magnesium degradation impurity product; and recrystallizing the crude product from an alcohol-water mixed solution to obtain a refined esomeprazole magnesium degradation impurity product. The method first performs site-specific oxidation of the 2-position alcoholic hydroxyl group of 3,5-dimethyl-2-hydroxymethyl-4-pyridone to a 2-position aldehyde group, and then site-specifically oxidizing the 2-position aldehyde group to a 2-position carboxyl group. The two-step oxidation process does not affect the C=C double bond in the pyridone. The method of the present invention is used to prepare esomeprazole magnesium by degrading impurities, with a total yield of more than 60% and a purity of more than 99%.

The invention discloses a pharmaceutical composition containing escomeprazole magnesium and mosapride citrate and a preparation method of the pharmaceutical composition, the pharmaceutical composition comprises an escomeprazole magnesium layer and a mosapride citrate layer, and optionally, the pharmaceutical composition further comprises an isolating layer arranged between the escomeprazole magnesium layer and the mosapride citrate layer; the esomeprazole magnesium layer comprises esomeprazole magnesium and auxiliary materials, the auxiliary materials comprise a filling agent and an adhesive, and the mass ratio of the filling agent to the adhesive in the esomeprazole magnesium layer is (0.1-20): 1, preferably (0.1-10), preferably (1-5): 1, and more preferably (3-3.5): 1. The pharmaceutical composition containing escomeprazole magnesium and mosapride citrate is designed, so that the pharmaceutical composition has the advantages of good stability, low impurity content, good content uniformity and the like, and the total impurity content is not more than 0.20% within 6 months of acceleration.

The invention provides an escomeprazole magnesium enteric-coated preparation and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The preparation method comprises the following steps: mixing magnesium carbonate and microcrystalline cellulose for first extrusion to obtain a first extrudate; mixing escomeprazole magnesium, microcrystalline cellulose, dextrin and hydroxy propyl distarch phosphate, and carrying out second extrusion to obtain a second extrudate; the mass ratio of dextrin to hydroxy propyl distarch phosphate is greater than or equal to 3; the first extrudate and the second extrudate are mixed to be extruded and rounded, the obtained pellet core is coated with a coating solution to form a coating layer, the obtained coated pellet core is mixed with a second lubricant, the escomeprazole magnesium enteric-coated preparation is obtained, and no isolation layer exists between the pellet core and the coating layer. By adopting the method disclosed by the invention, the coating time efficiency can be greatly shortened, the loss of raw and auxiliary materials in the coating process is effectively reduced, the production efficiency and the product yield are improved, and the bioavailability of drugs can be improved.