RU2285542C1 - Method for preparing enterosorbent - Google Patents

Abstract

FIELD: medicinal and pharmaceutical industry.

SUBSTANCE: method involves mixing polyphepan with a binding agent, drying a mixture and tabletting. Lactose is used as a binding, slipping and lubricating agent. After mixing components the prepared mixture is granulated and wetted granules are fed for drying up to residual moisture value 8%, not above. After drying termination granules are milled to particles size less 3.0 mm and then crushed granules are fed for tabletting and tablets with weight 0.5 g (± 0.025 g) are made of the following composition, g: polyphepan (as measure for dry matter), 0.35-0.40, and lactose, the balance. Invention provides retaining the sorption activity of polyphepan and to simplify the process.

EFFECT: improved preparing method.

1 ex

Description

The invention relates to the medical and pharmaceutical industries and can be used for the manufacture of dosage forms of enterosorbents based on medical hydrolysis lignin.

Known composite enterosorbent and method for its preparation (RU 2234931, 2002.07.29, A 61 K 35/78). The enterosorbent in the form of a powder mixture contains hydrolytic lignin, microcrystalline cellulose, pectin and highly dispersed silicon dioxide in the following ratio of components, wt.%: Hydrolytic lignin 25.0-35.0, microcrystalline cellulose 25.0-35.0, highly dispersed silicon dioxide 25 0-35.0, pectin 4.0-6.0. Enterosorbent can be made in the form of tablets with the addition of starch 2.0-4.0% and calcium or magnesium stearate 0.5-1.0%. To obtain an enterosorbent, hydrolytic lignin, additionally moistened to a moisture content of 70%, is mixed sequentially with pectin, microcrystalline cellulose and highly dispersed silicon dioxide, dried to a moisture content of 5-9% and, if necessary, tabletted with a mixture of starch and magnesium or calcium stearate.

A known method of producing enterosorbent (RU 2084236, 1996.02.20, A 61 K 35/78). The method allows to obtain medical lignin in tablet form, for which an aqueous solution of a pharmaceutically acceptable binder is prepared and medical lignin is mixed with it. The mixture is dried to a residual moisture content of at least 4%, at least until the binder solution disappears from it, and then it is granulated and pelletized. The amount of binder and the pressure value during tabletting are selected to ensure pharmaceutically acceptable values of strength and disintegration of the final product, but the amount of binder should not be less than 1.0% with respect to the dry residue of the original lignin. In some special cases, it is possible to moisten and / or mix lignin with water in advance, and a binder solution in a mixture with lignin can be obtained directly by binder powder mixing in lignin with water. The method is selected as a prototype.

The disadvantages of the known methods for producing enterosorbents based on lignin-containing raw materials in tablet form include the following:

- a significant drop in sorption ability, due to the need for a drying step before tabletting, during which irreversible changes in the structure of the sorbent occur - the developed inner surface of the pores decreases sharply and partially becomes inaccessible for interaction with the sorbate,

- the need for introducing into the enterosorbent additives that perform the functions of a binder, sliding and lubricating substance during pressing, which complicates the process of obtaining a multicomponent finished preparation, on the one hand, and creates an additional negative physiological effect in the pathological condition of the gastrointestinal tract (GIT), other.

The tasks to which the invention is directed are to create a new method for producing enterosorbent based on lignin-containing raw materials in tablet form, which allows:

- maintain the maximum sorption ability of polyphepan (medical hydrolysis lignin),

- simplify the manufacturing process,

- to qualitatively improve the pharmacological properties of enterosorbent and expand the possibilities of its use in medical practice.

The tasks are solved as follows.

The method of producing enterosorbent involves mixing polyphepan with a binder, drying the mixture, tabletting, and characterized in that milk, lactose, is used as a binder, sliding, lubricating component, and after mixing the components, the prepared mixture is granulated and the wet granules are dried to residual moisture no more than 8%, at the end of drying, the granules are crushed to a particle size of less than 3.0 mm, fed to tabletting and get tablets weighing 0.5 g (± 0.025 g) of the composition of the components, g:

Polyphepan (in terms of dry matter) 0.35-0.40 Milk sugar (lactose) Rest.

The method of obtaining includes the following technological operations:

- passed through a sieve lactose and polyphepan (substance) in the required proportions served in the mixer,

- lactose and polyphepan are mixed in the mixer until mass is homogeneous,

- the prepared mixture is portioned into the granulator, from which the wet granules are poured into the drying drums, weighed and transferred to the drying stage,

- drying of the wet granulate is carried out in the dryer for 1.0-1.3 hours to a residual moisture content of not more than 8% due to purging with air purified from impurities and heated to a temperature of 90-100 ° C. After drying, the granules from the drying drums are poured into containers and fed to the grinding stage.

- dry granules are crushed in a disk mill to a particle size of less than 3 mm The milled granules are tableted.

- periodically check the quality of the tablets according to the following indicators: the average weight of one and 20 tablets, every 2 hours; tablet strength for abrasion and disintegration, every 4 hours.

- the finished tablets are delivered to the warehouse.

Main characteristics of the obtained enterosorbent:

1. Composition, g

Polyphepan (in terms of dry matter) 0.35-0.40 Milk sugar Rest.

2. Dosage form: tablets of dark brown color, flat-cylindrical with a bevel for oral administration.

3. Disintegration - not more than 30 minutes.

4. Adsorption capacity - not less than 0.01 g of methylene blue per 1 tablet in terms of dry matter.

Technological decisions made in the production of the tablet form of polyphepan allowed to qualitatively improve the pharmacological properties of the drug and further expand the possibilities of its use in medical practice.

Polyphepan is a soft-skeletal sorbent and, when dried, significantly loses its sorption capacity by reducing porosity, which subsequently does not completely recover. In this regard, the need arose to develop such a dosage form that allows you to maintain a high sorption capacity of polyphepan for a long time and is simultaneously convenient for the consumer. The tablet form of the preparation, which contains lactose, which fills the micropores of polyphepan, which prevents the decrease in the chemisorption activity of polyphepan, is most suitable for such requirements.

In the composition with lactose, polyphepan does not have absolute contraindications, it may be allowed for use by persons with a limited intake of sugar, including patients suffering from certain forms of diabetes. The use of lactose in the composition of the tablets also eliminates the need for the introduction of any fillers as binders, sliding and lubricating additives. Fully absorbed by the body, lactose serves as a source of energy, which is especially important for gastrointestinal upsets, when the natural processes of digestion and absorption are disrupted, and the body is unable to properly absorb food.

Example

Enterosorbent tablets 0.375 g are allowed for use by adults and children, prescribed an hour before a meal or other medicines. The daily dose of 0.3-0.6 g / kg of body weight is divided into three to four doses. Average doses: for infants, 1 tablet; children from 1 to 7 years old - 2 tablets, from 7 years and older, as well as adults - 4-6 tablets 3-4 times a day.

In acute conditions, depending on the severity of diarrheal syndrome, the course of treatment is 3-7 days (until the symptoms of intoxication or stool normalize), in case of allergic diseases and chronic intoxications - courses of 10-15 days with breaks of 7-14 days, after consultation with a doctor.

The proposed method for producing a dosage form of an enterosorbent is characterized in that:

- the therapeutic combination includes, in the form of an associated active ingredient, lactose in the form of a crystalline powder. At the molecular level, lactose reversibly binds to the active sites of the developed complexly branched inner surface of the pores of the sorbent, thereby preserving their original geometry inherent in the sorbent in the wet state. Due to this, the high sorption activity of polyphepan does not decrease during subsequent drying, which is a prerequisite for further tableting. In the gastrointestinal tract, the tablet disintegrates easily; lactose reversibly bound to the sorbent becomes available for absorption by the body. At the same time, surface areas of the sorbent are freed and re-activated to interact with toxicants (with the sorbate). Thus, it is possible to maintain the fine structure of the sorbent without changes, to ensure maximum sorption activity,

- the ratio of the components is selected so that the mixture is well pressed with the formation of durable, easily disintegrating in the gastrointestinal tract, tablets that fully comply with the requirements of the State Pharmacopoeia of the XI edition,

- mixing of the starting components (dry and wet substances) is carried out in a special mixer in stages and in such a special way that the maximum uniformity of the finished mixture is achieved,

- tableting the mixture, characterized in that as a binder, a sliding and lubricating additive used a substance that favorably affects the state of the gastrointestinal tract, and not chemically inert substance. The regimen of the tabletting (pressing) process is selected in a special way and is carried out so that the tablets obtained by their uniformity, appearance, disintegration and their strength characteristics fully comply with the requirements of the State Pharmacopoeia of the 11th edition.

Claims (1)

A method of producing enterosorbent, comprising mixing polyphepan with a binder, drying the mixture, tabletting, characterized in that milk, sugar (lactose) is used as a binder, sliding, lubricating component, and after mixing the components, the prepared mixture is granulated and the wet granules are dried to residual moisture not more than 8%, after drying, the granules are crushed to a particle size of less than 3.0 mm, fed to tabletting, and tablets are obtained weighing 0.5 g ± 0.025 g of the composition of the components, g: Polyphepan (in terms of dry matter) 0.35-0.40 Milk sugar (lactose) Rest