51 results about "Metoprolol Succinate" patented technology

The present invention is a new stable extended release drug composition particularly suitable for use as a beta-adrenoreceptor antagonist agent. The present invention is specifically a drug composition comprising a pharmaceutical, a methacrylic acid copolymer and a matrix forming agent, and a method for manufacturing same. When applied to highly soluble drugs like metoprolol succinate, the resulting drug composition is characterized by an extended-release profile.

The invention discloses a metoprolol succinate sustained-release capsule, consisting of a capsule shell and contents; the contents comprise a metoprolol succinate sustained-release pellet; the metoprolol succinate sustained-release pellet comprises a metoprolol succinate contained pill core and a sustained-release coating layer coated outside the metoprolol succinate contained pill core; the metoprolol succinate contained pill core is prepared by using metoprolol succinate as the active ingredient and mixing with an auxiliary material, wherein the weight ratio of the metoprolol succinate to the auxiliary material is 1:1.5 to 1:3. The metoprolol succinate sustained-release medicine disclosed by the invention is stable and the expected effects of all release behaviors in acid, alkaline and water can be achieved. The invention further discloses a method for preparing the metoprolol succinate sustained-release capsule; compared with the prior art, the process is simpler and has good operability and reproducibility.

Belonging to the field of pharmaceutical chemistry, the invention specifically relates to a method for preparing (S)-metoprolol succinate. The method comprises the steps of: pumping hydroxyphenylethyl methyl ether and (R)-chloropropylene oxide into a reaction vessel, and during the reaction process, pumping a reaction feed liquid into an external circulating dewatering system loaded with a dewatering agent for circulating dewatering, reacting the prepared (S)-3-[4-(2-methoxyethyl) phenoxyl]-1, 2-epoxypropane with isopropylamine so as to obtain an (S)-metoprolol base; mixing the (S)-metoprolol base with succinic acid, thus obtaining (S)-metoprolol succinate. During the first step of reaction in the invention, water generated in the reaction process can be effectively removed through the external circulating dewatering device, and the loss of (S)-3-[4-(2-methoxyethyl) phenoxyl]-1, 2-epoxypropane is reduced, thus realizing simple and fast production of low energy consumption. By the method of the invention, the conversion rate of the first step product (S)-3-[4-(2-methoxyethyl) phenoxyl]-1, 2-epoxypropane is over 90%, the final yield of (S)-metoprolol succinate is greater than 75%, and the utilization rate of the reaction substrate is obviously enhanced.

The invention belongs to the technical field of drug preparations, and relates to a Metoprolol succinate sustained release tablet and a preparation method thereof. The sustained release tablet includes a tablet film coating material and a tablet core coated with the coating, the tablet core comprises a pellet and accessories, the pellet comprises, from the inside to the outside, a blank pill core,a drug-loading coating layer, a sustained release coating layer and a protective coating layer, the drug-loading coating layer comprises Metoprolol succinate and a drug-loading pellet coating adhesive, the sustained release coating layer comprises a sustained release pellet coating layer coating material, a pore forming agent, a plasticizer and an anti adhesion agent, the protective coating layerincludes a protection pellet coating adhesive, the accessories include a filler, a disintegrating agent and a lubricating agent. The sustained layer of the release tablet is externally wrapped with the protective layer, and the problems of slow release ability reduction and unqualified content uniformity caused by excess fluidity and the like due to the damage of the sustained release layer can be solved.

The invention provides metoprolol succinate sustained-release tablets which can be released smoothly and a preparation method thereof, and each metoprolol succinate sustained-release tablet comprises 100 parts by weight of metoprolol succinate, 200-1000 parts by weight of hydroxypropyl methylcellulose and 5-150 parts by weight of carbomer. A hydrophilic gel skeleton is adopted as a sustained-release means, and mixture of the hydroxypropyl methylcellulose and the carbomer is taken as blocking material, thereby being applicable to industrial production. Compared with the commercially available sustained-release tablets, the metoprolol succinate sustained-release tablets have similar in vitro release characteristic.

The invention relates to the field of drug preparations, and discloses a preparation method for a metoprolol succinate sustained release preparation, and a preparation method thereof. The method comprises the following steps: firstly, coating solution with well prepared raw materials and auxiliary materials onto blank pellets to form a medicating layer, coating a well prepared swelling layer and a sustained release layer on the medicating layer, and finally filling the coated pellets into hard capsules. The method is simple to operate, short in production period, high in efficiency, low in cost, controllable in process, the pellets are evenly coated, the appearance is round and normal and uniform, the stability is good, and the sustained release preparation is convenient to use and used for fully reducing the drug use frequencies of patients with hypertention and angina.

The invention provides metoprolol slow-release microsphere, slow-release medical composition and a preparation method of the metoprolol slow-release microsphere. The metoprolol slow-release microsphere comprises 8-40wt% of active pharmaceutical ingredients and 60-92wt% of slow-release materials, wherein the active pharmaceutical ingredients contain metoprolol succinate, metoprolol tartrate or metoprolol hydrochloride, and the slow-release materials include 65-75wt% of ethyl cellulose and 25-35wt% of poly amino methacrylate. The active pharmaceutical ingredients and the slow-release materials are dissolved in an organic solvent to prepare microsphere, then the microsphere and an excipient are mixed to be pressed into tablets or manufactured into capsules to achieve the slow-release medicalcomposition containing the metoprolol slow-release microsphere. The medical composition is simple in prescription, low in toxicity, high in package rate, strong in controllability, good in reproducibility and low in cost.

The present invention provides extended release pharmaceutical compositions of a beta blocker such as, but not limited to, metoprolol succinate as the active ingredient, optionally also comprising a diuretic such as but not limited to hydrochlorothiazide, and methods of preparing such extended release pharmaceutical compositions.

The invention relates to a preparation method of metoprolol succinate, which comprises the following steps: reacting para-methoxylethylphenol with sodium hydride or sodium ethylate in tetrahydrofuran to obtain para-methoxyl sodium phenate; reacting para-methoxylethyl sodium phenate with epoxy chloropropane in toluene or the tetrahydrofuran to obtain 1-(2, 3-epoxy propoxyl)-4-(2-methoxylethyl)-benzene, and then, reacting the 1-(2, 3-epoxy propoxyl)-4-(2-methoxylethyl)-benzene with isopropylamine in isopropanol or the toluene to obtain metoprolol alkali; and in absolute ethyl alcohol or chloroform, reacting the metoprolol alkali with succinic acid to obtain the metoprolol succinate.

The invention provides a novel skeleton sustained release tablet containing metoprolol succinate, relating to a dual-layer skeleton sustained release tablet with metoprolol succinate of an auxiliary layer capable of assisting in adjusting the release speed. By using a novel skeleton sustained release tablet technology, the auxiliary layer for assisting in adjusting the release speed is added on the basis of the traditional skeleton piece and a long-acting sustained release tablet of the metoprolol butanedioic acid salt can be successfully prepared. The release speed of the obtained sustained release tablet containing metoprolol succinate amazingly represents favorable linearity and completely meets the United States Pharmacopoeia (USP30) standard. Compared with products of astrazeneca coming into market, the in vitro release behavior of the novel skeleton sustained release tablet is quite close; in addition, the novel skeleton sustained release tablet has simple process and low cost.

The present invention relates to sustained release solid pharmaceutical composition comprising antihypertensives, in particular, Metoprolol succinate or pharmaceutically acceptable derivatives thereof and a process for preparing such a formulation. The present invention is a composition comprising Metoprolol succinate or its pharmaceutically acceptable derivatives thereof and the composition releases the drug over 24 hours. The composition further comprises hydrophilic polymer matrix based tablets. The present invention describes a sustained release tablet comprising sustained release matrix comprising of gelling agents comprising at least one hydrophilic polymer with one or more gum and gum derivatives.

The invention discloses a crystal form of metoprolol succinate and a preparation method thereof. The X-ray diffraction of the crystal form of metoprolol succinate has peaks when the reflection angle 2theta is 7.4 +/- 0.2, 14.4 +/- 0.2, 20.4 +/- 0.2, 21.5 +/- 0.2 or 24.4 +/- 0.2. The crystal form of metoprolol succinate provided by the invention has high content (or purity), low impurity content and stable quality and provides safety guarantee for clinical application of a metoprolol succinate medicine.

The invention discloses metroprolol succinate dropping pills and a preparation method thereof. The metroprolol succinate dropping pills are prepared from the following raw materials in parts by weight: 1-3 parts of metroprolol succinate, 2-4 parts of beta-cyclodextrin, 8-18 parts of matrix, 1-3 parts of a stabilizer and 1-3 parts of condensate. According to the metroprolol succinate dropping pills and the preparation method thereof, provided by the invention, the prepared metroprolol succinate dropping pills can quickly release in vivo to achieve the therapeutic effect, and can further maintain a stable and lasting therapeutic effect; besides, the metroprolol succinate dropping pills are low in cost, good in effect and good in bioavailability.

The invention belongs to the technical field of medicine and relates to a method for preparing metoprolol succinate sustained-release pellet tablets. The method includes steps: dissolving metoprolol salt and a bonding agent into an appropriate solvent to prepare coating solution for a medicine layer; dissolving a sustained-release coating material, a plasticizer and a pore forming agent of a sustained-release compression-resistant layer into coating solution solvent to prepare coating solution for the sustained-release layer; adding appropriate auxiliary materials, well mixing, tabletting and coating. The metoprolol succinate sustained-release pellet tablets keep active component release speed unchanged even being split for administration, and active components can be continuously and slowly released within 24 hours.

An extended release pharmaceutical composition comprising metoprolol succinate and at least two pharmaceutically acceptable excipients, wherein the first pharmaceutically acceptable excipient is an extended release agent; the second pharmaceutically acceptable excipient is selected from a binder, a diluent and mixtures thereof; and metoprolol succinate is in a crystalline form having a D50 ranging from 5 to 16 microns and a D90 below 50 microns.

The invention provides a spray-drying method for preparing metoprolol succinate sustained-release capsules. The method comprises the following steps of: (1) dispersing metoprolol succinate in an oil phase uniformly, and emitting ultrasound to obtain a suspension, wherein the oil phase contains 1 to 10 percent of surfactant; (2) dissolving a macromolecular capsule material in an aqueous solution of ethanol, adding an antisticking agent, a plasticizer and a dispersing agent, stirring uniformly, filtering and preparing an external water phase for later use; and (3) adding the suspension obtainedin the step (1) into the ethanol solution obtained in the step (2), homogenizing and emulsifying to obtain a metoprolol succinate suspension/oil/water (S/O/W) multi-emulsion spray liquid, and spray-drying. The metoprolol succinate sustained-release capsules are rounded in appearance, smooth and clean in surfaces, high in flowability and encapsulation rate, lasting in medicinal effect and high in stability, have the grain diameter of between 30 and 300 micrometers, can control burst release effectively, have an obvious sustained-release effect, and are suitable for large-scale industrial production.

The invention provides a method for tabletting metoprolol succinate pellets. The method comprises the following steps of: applying medicine on a blank pellet core, coating a slow release layer, addingadditional auxiliary materials, and performing mixing and tabletting. The blank pellet core consists of a main material, an adhesive and a solvent. The main material, the adhesive and the solvent account for 60 to 90 percent, 10 to 30 percent and 2 to 15 percent of the total mass respectively. The main material consists of microcrystalline cellulose and silicon dioxide. The preparation method ofthe blank pellet core is prepared by a centrifugal granulation method. The obtained blank pellet core has excellent roundness and brittleness, can be used for preparing and tabletting sustained-release pellets, the breakage rates of pellets and sustained-release films before and after tabletting are low, the release behavior before and after tabletting has no obvious change, and the technical requirements of pellet tabletting are met. Meanwhile, microcrystalline cellulose 101, microcrystalline cellulose 200 and hydroxypropyl cellulose are added in the tabletting link, so that the layering of the pellets and blank matrix in the tabletting link is avoided, and the problem of brittleness which is easy to occur in the pellet tabletting link is solved.

The invention relates to a method for preparing high-purity metoprolol succinate, which adopts a single solvent system to prepare the metoprolol succinate in a reverse dropping mode. The method is simple and convenient to operate, stable in process, high in salifying yield and purity, low in process cost, and has good practical value. A single conventional solvent is adopted, so that post-treatment and solvent recovery are facilitated, and the method is environment-friendly.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a synthesis method of metoprolol succinate isomer impurities. According to the synthesis method, p-methoxyethyl phenol is used as a raw material, and the metoprolol succinate isomer impurity is prepared through five steps of reactions including a condensation reaction, a ring-opening reaction, an oxidation reaction, a reductive amination reaction and a hydrolysis reaction. The synthesis method provided by the invention comprises five steps of reactions, the raw materials are easy to obtain, the total yield is greater than 30%, and contribution is made to strict control of the impurity content of the metoprolol succinate isomer by adopting an external standard method; the synthesis method has the advantages of simple operation, mild reaction conditions and high product purity, is suitable for drug quality research, and provides a guarantee for improving the quality of metoprolol succinate bulk drugs.

The present invention provides an extended-release capsule dosage form of metoprolol succinate in the form of coated discrete units and processes for their preparation.