Pharmaceutical composition having anticonvulsant and psychotropic action, and how you can get

 

(57) Abstract:

The invention relates to the field of medicine and relates to a pharmaceutical composition having anticonvulsant and psychotropic action. The song is performed in the form of a solid dosage form that contains carbamazepine, starch, oxypropylation, stearic acid and/or its salt. Get a new pharmaceutical composition by moistening the mixture of active substance - carbamazepine with auxiliary substances, starch and oxypropylated and subsequent drying, dusting of dry granules stearic acid and/or its salt and pelletizing the mixture. The composition has improved resistance to abrasion and dissolves easily. 2 S. and 4 C.p. f-crystals, 1 table.

The invention relates to the field of medicine and is suitable for the treatment of epilepsy, trigeminal neuralgia, diabetes insipidus (in combination therapy) and prevention faznoprotekate affective disorders (manic-depressive psychosis and other psychotic disorders).

One of the major drugs acting on the Central nervous system, is carbamazepine (chemical name 5-carbamazepina activity of carbamazepine successfully combined with the availability of its spectrum antidepressant (timolepticheskoe) and normotimicheskoe psychotropic properties. The compound reduces the frequency and intensity of epileptic seizures and has an analgesic effect when the trigeminal nerve.

There are various forms of medicines on the basis of carbamazepine, for example, in the form of a polymer gel (U.S. patent No. 5980942, 1999), water (U.S. patent No. 6051253, 2000).

Known oral dosage form based on carbamazepine, comprising a core and a shell, in which there is a hole connecting the core with the surrounding environment (the Federal Republic of Germany patent No. 3725824, 1988). It contains carbamazepine, microcrystalline cellulose, oksipropilmetiltselljuloza, copolymer of vinylpyrrolidone and vinyl acetate (Kollidon VA64), polyethylene glycol with M. C. 5×106, sodium chloride, sodium lauryl sulfate and magnesium stearate, and the shell is composed of cellulose acetate and polyethylene glycol 4000. The disadvantages of this structure should be attributed rather complex technology of its production and the necessity of using micronized carbamazepine.

In the patent Switzerland No. 649080, 1985, describes a drug that contains carbamazepine, lactose, starch, gelatin, talc, magnesium stearate and silicon dioxide. However, the composition has a relatively low content is of the active substance, containing the foaming agent in combination with a softening agent in the aqueous solution and/or dispersion deposited on carbamazepine in the granulator, fluidized bed (patent RF №2141825). As the foaming agent is a mixture of polymethacrylates, and as a softener - glycerinated or triethylcitrate. Optionally, the dispersion of the foaming agent injected release agents, for example talc, and/or sprayed them later in the fluidized bed in the form of separate suspensions. Covered carbamazepine with other excipients (microcrystalline cellulose, polyvinylpyrrolidone, silicon dioxide, magnesium stearate) pressed into scored tablets or Packed in capsules. A disadvantage of the known forms is bad raspadaemost dosage forms.

The closest technical solution to the declared object is known pharmaceutical composition containing carbamazepine, starch, stearic acid and/or its salts and other additives target, used as Aerosil, glycerin, gelatin (RF patent 2157212, 2000). Well-known member of the tablets of the prototype is characterized by low abrasion resistance, and the presence of Aerosil significantly impairs the th invention is to provide a simple and accessible form-based medications carbamazepine, having improved abrasion resistance at the same time quick raspadaemosti in the water.

To solve this problem is proposed pharmaceutical composition in the form of a solid dosage form comprising as active ingredient carbamazepine and as excipients starch, oksipropilmetiltselljuloza, stearic acid and/or its salt.

The optimal ratio of ingredients is, wt.%:

Carbamazepine 62,5-80,0

Starch 15,0-30,0

Oxypropylation 1,0-7,0

Stearic acid and/or its salt is from 0.5 to 2.0

The claimed ratio of ingredients found experimentally and allows to obtain a technical result that is appropriate to the task. Thanks to the invention offer the pharmaceutical composition of carbamazepine has improved abrasion resistance (>99%) and dissolves easily. Raspadaemost in water for 3-5 minutes (when the normative requirement of no more than 15 minutes).

Used according to the invention, the starch may be potato and/or corn and/or rice and/or modified starch, such as, for example, nitroglycerol brand PR is respectfully a stearate or calcium.

The proposed pharmaceutical composition is in the form of solid dosage forms, preferably in the form of tablets that allows for maximum adaptability subsequent packaging and precision dosing of the active substance.

The way to obtain a new composition comprises wet granulating a mixture of carbamazepine, starch and oxypropylation, drying and dusting of dry granules. The wet granules are preferably dried to a residual moisture content of 1.5-3.5 percent. Higher humidity causes caking of the granules, making it difficult to obtain a homogeneous mixture and conducting tabletting, lower humidity increases rejection tablets (spalls, delamination). The dusting granulate produce stearic acid and/or its salt, preferably a mixture of stearinovokisly magnesium and stearic acid or stearinovokisly calcium. With the purpose of improvement of technological parameters tabletas mix the dry granules may be subjected to additional grinding, i.e., the dry granulation.

To make the proposed tool forms tablets obtained after dusting composition is pressed on a tablet machine.

The invention ilustrejosa potato starch (31.7 g) and oxypropylation (6,45 g) and stirred until a uniform distribution of moisture.

Wet pasta granularit on the device for producing granules and dried in the fluidized bed to a residual moisture content of 2%. Dry granules grind, optivault with a mixture of 0.6 g of stearic acid and 0.4 g stearinovokisly magnesium and tabletirujut. Get pills carbamazepine with an average weight 0.28 g, which correspond to requirements of normative documentation and have a shelf life of more than 2 years and 6 months. Raspadaemost tablets 3 min (according to requirements of normative documents of no more than 15 min), the content of carbamazepine in one pill 0,199 g (according to the requirements of normative documents from 0.19 to 0.21 g), impurities are absent, the abrasion resistance and 99.8%.

Examples 2-4 perform similarly, with the difference that in example 2, use corn starch in example 3, a mixture of potato and modified starch brand "Primogel" and in example 4 as a moisturiser apply a 3% solution of oxypropylation in the water. The results of production are presented in the table. The obtained tablets satisfy regulatory requirements.

1. Pharmaceutical composition in the form of solid dosage forms with anticonvulsant and psychotropic action, which is a new acid and/or its salt, characterized in that it further comprises oxypropylation in the following ratio of ingredients, wt.%:

Carbamazepine 62,5-80,0

Starch 15,0-30,0

Oxypropylation 1,0-7,0

Stearic acid and/or its salt is from 0.5 to 2.0

2. The pharmaceutical composition under item 1, characterized in that it is made in tablet form.

3. The pharmaceutical composition under item 1 or 2, characterized in that it contains as a salt of stearic acid magnesium and/or calcium salts.

4. The method of obtaining the pharmaceutical composition described in any of the p. 1 to 3, comprising wet granulating a mixture of the active substance - carbamazepine with auxiliary substances, starch and oxypropylated, and subsequent drying, dusting of dry granules stearic acid and/or its salt and tableting the mixture.

5. The method according to p. 4, in which the drying of the wet granulate is carried out to a residual moisture content of 1.5-3.5 percent.

6. The method according to p. 4 or 5, in which, after drying spend additional granulation.



 

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