RU2240120C1 - Pharmaceutical composition for improving cerebral circulation (vinpomaks)and method for its preparing - Google Patents

Abstract

FIELD: medicine, pharmaceutical technology, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition used for improvement of cerebral circulation and to a method for it preparing. The proposed composition comprises vinpocetin and accessory substances, such as calcium dihydrophosphate, collidon 25, CL, magnesium stearate and lactose. Invention provides the improvement of cerebral circulation due to selection of accessory substances. The prepared composition elicits some pharmacological good quality properties and improved physical-chemical properties that allow reducing loss in tablet making and elevating rate in tablet making.

EFFECT: improved preparing method, valuable medicinal properties of composition.

2 cl, 1 tbl, 2 ex

Description

The invention relates to the field of pharmacology and medicine, specifically to a pharmaceutical composition for improving cerebral circulation based on vinpocetine and a tablet dosage form based on it.

Vinpocetine (ethyl ester of apovincamic acid) is one of the most effective drugs for improving cerebral circulation (Mashkovsky MD Medicines, v.1, 1993, p. 505).

Vinpocetine is insoluble in water, but readily soluble in a 0.01 M hydrochloric acid solution, readily adsorbed in the digestive tract after its dissolution. To obtain a therapeutic effect, a long (within several months) course of treatment is required. Therefore, the development of dosage forms intended for administration per os, in particular pharmaceutical compositions suitable for tabletting, is justified.

However, vinpocetine, like most drug substances, does not have the ability to direct tabletting, which requires the selection of auxiliary substances that provide the pharmacological and physicochemical properties necessary for this dosage form.

Closest to the proposed invention according to the methodological approach (increasing the bioavailability of this drug substance by increasing its dose in the gastrointestinal tract in a short period of time, “in pulsed mode”) is a pharmaceutical composition for improving cerebral circulation containing vinpocetine, potato starch and milk sugar as basic fillers, potato paste as a binder for wet granulation and a mixture of aerosil and magnesium stearic acid for dusting dry granulate, p In the following ratio of components (parts by weight):

Vinpocetine 1.0

Aerosil 0.1-1.64

Starch 4.1-12.4

Lactose (milk sugar) 6.8-24.8

Magnesium stearic acid 0.05-0.2

The method consists in mixing vinpocetine with a main filler (a mixture of starch and milk sugar), moistening with starch paste, wet granulation, drying, dry granulation, dusting the granules with a mixture of aerosil and magnesium stearate, tabletting (Russian patent No. 2155039, A 61 K 31/4375 , A 61 K 9/20 dated 12/14/1999).

Despite the fact that the content of vinpocetine in tablets according to this invention exceeds that in other known tablet dosage forms by almost 4 times, however, for some cases it is insufficient. Firstly, because it does not allow to achieve sufficiently high doses of vinpocetine in the gastrointestinal tract even at high rates of tablet disintegration and dissolution of the active principle, and secondly, because a high placebo content in tablets with long courses of treatment is unsafe (this is especially true for silicon-containing components )

The selection of excipients in this dosage form also does not give it such a property as plasticity, which is manifested both in the increased percentage of defective and rejected tablets, and in the absence of such an important utilitarian property as linguality.

An inventive task is to create a pharmaceutical composition based on vinpocetine, suitable for tabletting, with improved properties: bioavailability by increasing the concentration of the active principle and maintaining or improving the characteristics of the disintegration rate of the tablets in the gastrointestinal tract and the completeness of dissolution; to improve ductility while maintaining other important physical and chemical parameters, such as hardness, strength, stability over time, etc., to reduce side effects by reducing the placebo content, which is especially important for long courses of treatment.

The inventive task is solved by the qualitative and quantitative selection of excipients.

A pharmaceutical composition for improving cerebral circulation, suitable for tabletting, containing vinpocetine, as well as magnesium stearic acid and lactose as auxiliary substances is patented, the difference of which is that it additionally contains calcium dihydrogen phosphate, collidone 25 (polyvinylpyrrolidone with an average M.M. = 25700 , water-soluble polymer) and collidone CL (polyvinylpyrrolidone with an average M.M. = 55000, water-insoluble polymer) in the following ratio of components (parts by weight):

Vinpocetine 1-2

Calcium dihydrogen phosphate 2.50-5.00

Collidon 25 0.28-0.22

Collidone CL 0.10-0.14

Magnesium stearic acid 0.07-0.09

Lactose 6.80-12.00

Also patented is a method for producing a pharmaceutical composition for improving cerebral circulation containing vinpocetine and pharmaceutically acceptable target additives, which includes the steps of mixing the active principle with the main excipients, wet and dry granulation, dusting the dry granulate and tabletting, and characterized in that the main excipients are a mixture of lactose and calcium dihydrogen phosphate at a ratio of 2.4-2.8: 1, an aqueous solution of collidone is used as a humidifier in granulation 25, with its weight ratio with humidified 3-3.5: 1, and powdering dry granulate is carried out with a mixture of magnesium stearate and Kollidon CL.

The composition of the ingredients, the characteristics of the method are optimal, selected empirically and provide the above properties of the finished dosage form.

In the patentable composition, the ratio of active substance to auxiliary components is 1-2: 10.25, which is almost 5 times more than in the prototype; high disintegration of the tablets remains, while the dissolution of the active principle occurs at a higher rate (99-99.2% of vinpocetine dissolves in less than 30 minutes, in the prototype in 75 minutes). The composition provides not only high tablet strength (tablets are 2 times stronger than in the prototype), but also high plasticity due to the use of highly plastic polymers, which in turn leads to lower losses during tabletting, allows you to increase the tabletting speed and provides linguality (easy swallowability) ) tablets.

The invention is illustrated by examples. Data on the compositions obtained by the method in examples 1 and 2, and their properties are summarized in the table.

Example 1

A mixture of sifted powders of vinpocetine 10.35 g, calcium dihydrogen phosphate 25.2 g, lactose 64.52 g is moistened with a 10% solution of collidone 25 and mixed until the moisture is evenly distributed. The wet mass is granulated (granule diameter 2 mm) and the granules are dried to a residual moisture content of 1.0-2.0%. Then the granules are wiped through a sieve with a hole diameter of 0.6 mm 0.71 g of magnesium stearate and 1.41 g of collidone CL are added and mixed until a homogeneous mass is obtained, which is transferred to tableting in an impact type machine. Obtain 103.14 g with the release of 98.5% of tablets with an average weight of 0.14 g, which satisfy the requirements for pharmaceuticals. Data on the pharmaceutical composition and its physico-chemical properties are shown in the table.

Example 2

The operations of the method are the same as in example 1, while 20.8 g of vinpocetine, 50.4 g of calcium dihydrogen phosphate, 121.7 g of lactose are introduced, moistening is carried out with a 5% solution of collidone 25. To dust dry granules, 0.91 g of magnesium stearate is introduced and 1.01 g of collidone CL. 191.6 g of tablets are obtained, which is 98.2% of the yield. Data on the composition and its properties in the table.

The resulting pharmaceutical composition meets the requirements of GF X1 (in appearance, disintegration, dissolution, uniformity of dosage and other indicators), is stable during storage and has a shelf life of at least 3 years.

Claims (2)

1. A pharmaceutical composition for improving cerebral circulation, suitable for tabletting, containing vinpocetine, as well as magnesium stearic acid and lactose as auxiliary substances, characterized in that it additionally contains calcium dihydrogen phosphate, collidone 25 and collidone CL in the following ratio, wt.h .: Vinpocetine 1 Calcium dihydrogen phosphate 2.50-5.00 Collidon 25 0.28-0.22 Collidone CL 0.10-0.14 Magnesium stearic acid 0.07-0.09 Lactose 6.80-12.00 2. A method of obtaining a pharmaceutical composition for improving cerebral circulation containing vinpocetine and pharmaceutically acceptable target additives, which includes the steps of mixing the active principle with the main excipients, wet and dry granulation, dusting the dry granulate and tabletting, characterized in that the main excipients are a mixture of lactose and calcium dihydrogen phosphate at a ratio of 2.4-2.8: 1, an aqueous solution of collidone 25 at its ratio is used as a humidifier in granulation water with a moistened mass of 3-3.5: 1, and dusting of the dry granulate is carried out with a mixture of magnesium stearic acid and collidone CL.