Dosage form with antiarrhythmic and antianginal action, and method of its manufacture

 

(57) Abstract:

The invention relates to the field of pharmaceutical industry and relates to the production of solid dosage forms of drugs to reduce the resistance of the coronary arteries and increase coronary blood flow, ischemia of heart contractions, reducing the need of oxygen, increase energy reserves attacks. The invention consists in that the dosage form contains the following components: amiodarone hydrochloride, starch, microcrystalline cellulose, polyvinylpyrrolidone, maltodextrin, magnesium stearinovokisly, Primerose, sugar, dairy. Disclosed is also a method of manufacturing the aforementioned dosage forms. The invention provides increased bioavailability, stability obtained dosage forms. 2 S. p. f-crystals, 1 table.

The invention relates to medicine, in particular to a pharmacy, can be used in the manufacture of solid dosage forms of drugs to reduce the resistance of the coronary arteries and increase coronary blood flow, ischemia of heart contractions, reducing the need of oxygen, increase energy reserves attacks.

The way to obtain this form involves mixing active with AIDS, the subsequent hydration of the mixture and granulating the obtained hydrated mixture. Then the granulate is dried, optivault and tabletirujut.

The disadvantages described dosage form, and method of its manufacture is that it has low bioavailability, low storage stability due to the low strength of the tablets.

The objective of the invention is the elimination of all the above drawbacks.

The problem is solved dosage form with antiarrhythmic and antianginal action, containing as active amiodarone hydrochloride, and as excipients starch, magnesium stearinovokisly and polyvinylpyrrolidone, while it additionally loony sugar, in the following ratio, wt.%:

Amiodarone hydrochloride 40,0-80,0

Starch 4,0-7,0

Microcrystalline cellulose 3,0-10,0

Polyvinylpyrrolidone 0,1-2,0

Maltodextrin 1,0-5,0

Magnesium stearinovokisly 0,5-2,0

Primerose 1,0-5,0

Milk sugar 10,4-29,0

The task is also solved by a method of manufacturing the aforementioned dosage forms, in accordance with which the mix of amiodarone hydrochloride, starch, microcrystalline cellulose and lactose, the resulting mixture is moistened with a solution of maltodextrin with polyvinylpyrrolidone, re-mix, damp granulation, subsequent drying, dry granulation, the powder mixture primality and magnesium stearinovokisly and tableting.

The invention consists in the following.

Amiodarone (Amiodaronum) - a substance with the chemical formula [2-butyl-3-benzofuranyl]-[4-(2-diethylaminoethoxy)-3,5-goodfeel]-ketone hydrochloride. Amiodarone was originally investigated in koronarorasshiryayuschego (antianginal) tools for the treatment of chronic forms of ischemic heart disease. Further complications were identified its properties and present the material means amiodarone values are not lost. The antianginal effect of amiodarone is partly due to its antispasmodic (vasodilator) and antiadrenergicheskim. He has a braking effect on a - and b-adrenergic receptors in the cardiovascular system, not causing complete their blockade. However, it raises the tone of the sympathetic nervous system. The drug reduces the resistance of the coronary arteries and increases coronary blood flow, reducing urezhaet heart, reduces the need for oxygen, increases energy reserves infarction (increases the amount of creationinterface, adenosine and glycogen). He slightly lowers peripheral vascular resistance and systemic blood pressure. Unlike drugs, completely blocking b-adrenergic receptors, amiodarone virtually no negative inotropic action. Like a number of other antianginal drugs have in varying degrees antiadrenergicheskoy activity, amiodarone reduces the sensitivity to over-stimulation of the sympathetic nervous system. The drug has a pronounced effect on the electrophysiological processes in the myocardium. It significantly lengthens the action potential of cardiomyocytes and, thus, ovei Purkinje fibers, as well as additional ways of carrying out of excitation. He can also slow down (diastolic) depolarization of the cell membrane of the sinus node and other cardiomyocytes and directly influence the mechanical heart.

Its content in the dosage form to achieve real results should be 40,0-80,0 wt.%.

As auxiliary substances forming the tablet, use lactose, polyvinylpyrrolidone, microcrystalline cellulose, potato starch, stearinovokisly magnesium, Primerose and maltodextrin.

Primerose is a sodium salt crosscarmelose and provides the necessary bioavailability of the drug.

Maltodextrin is a mixture of glucose, malt sugar and oligosaccharide in the form of a white hygroscopic cream powder, pleasant to the taste. Produced by the partial hydrolysis of starch using bacterial alpha-amylase.

Data supplements allow you to get a pellet mixture of the required quality and non-toxic for the organism.

The contents of all of the components are selected in such a way as to achieve the required quality pills (stability during storage) in order to NUU form an integrated humidifier (maltodextrin, together with low molecular weight polyvinylpyrrolidone and primality) allows to obtain tablets high strength with moderate pressing force and high bioavailability.

The set of operations in the way and their modes are selected in such a way as to simplify the method of manufacturing dosage forms without compromising their quality.

Uniform distribution of the dose of amiodarone is achieved by mixing the active ingredient with excipients (starch and microcrystalline cellulose). The improvement of the mechanical properties of the mixture and preventing its fractionation during pelletizing provided by introducing into the mixture a combined humidifier (maltodextrin and PVP), mixing, granulation and subsequent drying. Conducting dry granulation standardizes the mass of particle sizes, which ensures uniformity of products (tablets) by weight. Introduction primality when the powder mixture is required for the rapid destruction of the tablets in the stomach when it is receiving and maximize the bioavailability of the drug. Magnesium stearinovokisly should be introduced into the mixture in the last turn and is necessary to prevent sticking tablet mixture during compaction.

The invention is carried out as follows.

Pre-sifted amiodarone hydrochloride, microcrystallites the P>

Then the mass is moistened by a solution of maltodextrin with PVP and granularit.

The moist granulate is dried at a temperature of 50 to 55°C to a residual moisture of 2.0 to 3.0% and granularit.

The dry granulate optivault adding pre-sifted primality and magnesium stearinovokisly. The mixture is stirred until a homogeneous tablet mass.

Tablets weight tabletirujut receiving face of the tablet of risk and chamfer diameter of 10.0±0.3 mm, a weight of 0.33,

Example.

Pre-sifted amiodarone hydrochloride 25,0 kg, 3,064 kg of potato starch, 3,272 kg of microcrystalline cellulose and 7,734 kg of sugar of milk is stirred until a uniform distribution of components.

Then the mass of the hydrate by adding a 7% solution of maltodextrin with 1% PVP in the number 16,398 kg and granularit.

The moist granulate is dried at a temperature of 50 to 55°C to a residual moisture of 2.0 to 3.0% and granularit.

Dry the granulate in the number 39,535 kg optivault adding pre-sifted 0,810 kg primality and 0,364 kg magnesium stearinovokisly. The mixture is stirred until a homogeneous tablet mass.

Tablet mass is="ptx2">The table shows the most attractive composition obtained in accordance with the present invention pills.

Dosage form produced in accordance with the invention, has high bioavailability, as well as excellent storage stability due to the high strength of the tablets.

1. Dosage form with antiarrhythmic and antianginal action, containing as active amiodarone hydrochloride, and as excipients starch, magnesium stearinovokisly and polyvinylpyrrolidone, characterized in that it additionally contains as excipients microcrystalline cellulose, maltodextrin, Primerose and milk sugar in the following ratio, wt.%:

Amiodarone hydrochloride 40,0-80,0

Starch 4,0-7,0

Microcrystalline cellulose 3,0-10,0

Polyvinylpyrrolidone 0,1-2,0

Maltodextrin 1,0-5,0

Magnesium stearinovokisly 0,5-2,0

Primerose 1,0-5,0

Milk sugar 10,4-29,0

2. The method of manufacture of dosage forms with antiarrhythmic and antianginal action, bookmark the scientists of the mixture is moistened, re-mix, damp granulation, subsequent drying, dusting and tableting, characterized in that as auxiliary substances in the mixture is also used microcrystalline cellulose and lactose, moisturizing mixture is performed with a solution of maltodextrin with polyvinylpyrrolidone, after wet granulation and drying are conducted dry granulation, and the dusting implement the mixture primality and magnesium stearinovokisly.



 

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