RU2445963C2 - Pharmaceutical antidiabetic composition - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, and more specifically to an antidiabetic composition. What is offered is a pharmaceutical composition containing Glimepiride, poloxamer, sodium croscarmellose and other excipients - povidone, lactose monohydrate, microcrystalline cellulose, stearic acid salt and a colourant.

EFFECT: pharmaceutical composition is characterised by high therapeutic activity, satisfactory technical characteristics and shelf life of more than 2 years.

11 cl, 1 tbl, 1 ex

Description

The invention relates to medicine, specifically to an agent that can be used to treat diabetes.

Known pharmaceutical composition for the treatment of diabetes in the form of tablets, which contains glimepiride and excipients (lactose, pregelatinized starch, microcrystalline cellulose, hydroxypropylmethyl cellulose) [patent CN 101433524]. However, it is characterized by insufficient strength.

Known pharmaceutical composition for the treatment of diabetes, which contains glimepiride, disintegrant - sodium starch glycolate, and other excipients - filler / binder (microcrystalline cellulose, lactose monohydrate), a binder (polyvinylpyrrolidone), a lubricant (magnesium stearate) and dye - indigo carmine (Medicines in Russia: Reference, M .: AstraFarmService, 2008, p.236, prototype).

The objective of the invention is the creation of an antidiabetic drug based on glimepiride in the form of a solid dosage form, with an optimal combination of excipients, exhibiting high therapeutic activity and having a shelf life of more than 2 years.

The active substance in the proposed composition is glimepiride. Glimepiride is a hypoglycemic agent for oral administration of the sulfonylurea group of the third generation. Sugar-lowering drug. Provides a more physiological and safer treatment profile compared to previous generations. Glimepiride stimulates pancreatic beta cells, contributing to the mobilization and increased release of endogenous insulin, increases the number of insulin-sensitive receptors in target cells, and inhibits gluconeogenesis. Reduces the risk of retino-, neuro- and nephropathy.

To solve this problem, an antidiabetic composition is proposed containing glimepiride in a therapeutically effective amount, a disintegrant and other excipients, characterized in that it also contains poloxamer and croscarmellose sodium as a disintegrant. As excipients that act as a filler, binder, lubricant, the composition preferably contains lactose monohydrate, microcrystalline cellulose, polyvinylpyrrolidone, a stearic acid salt and a dye. As the latter, iron oxide red or iron oxide yellow is used.

A distinctive feature of the developed composition is that it contains poloxamer and sodium croscarmellose. Poloxamer, known as a solubilizer, we, in addition, was used as a binder in the tablet mixture. The joint use of poloxamer in an amount of from 0.025 to 1.5 mass. parts and the selected disintegrant in an amount of from 0.375 to 14.0 mass. parts (depending on dosage) allowed to stabilize the quality of the drug according to the indicator "Dissolution" during the expiration date. The disintegrant chosen by us with its mechanism of action (longitudinal swelling of the tablet) ensured reproducibility of the analysis results and reduced the dispersion of the “Dissolution” index values in each test series in comparison with the prototype (at a rate of at least 80% of the active substance in 15 minutes - from 94 to 99% in our preparation, from 88 to 99% - in the analogue drug). In addition, the introduction of poloxamer almost doubled the fracture strength of the tablets and reduced their fragility by an average of 1.5% compared to the prototype.

The preferred ratio of the ingredients of the claimed composition is, parts by weight per 1 m.h. glimepiride:

Glimepiride - 1

Croscarmellose sodium - 0.375-14.0

Poloxamer - 0.025-1.5

Povidone (polyvinylpyrrolidone) - 0.2-8.0

Lactose Monohydrate - 6.5-236.0

Microcrystalline cellulose - 1.5-36.0

Stearic acid salt - 0.05-12.0

Dye - 0.002-0.06

As polyvinylpyrrolidone (another name is povidone), collidone is preferably used. Preferably, calcium and / or magnesium stearate is used as a stearic acid salt, and iron oxide is yellow and / or iron oxide is red as a dye.

The claimed pharmaceutical composition is in the form of a solid dosage form, preferably in the form of a tablet.

Examples of the invention are presented in the Table.

Example 1. Due to the low dye content in the composition of the tablet mass, in order to achieve uniform staining of the tablets, a mixture of croscarmellose sodium and dye is separately prepared. For this, the pre-sieved dye powder is mixed with a small amount of sieved croscarmellose sodium powder and the resulting mixture is manually sieved three times through a sieve with a mesh size of 114 μm and mixed with the remaining croscarmellose sodium.

Pre-sifted powders of the substance glimepiride, lactose monohydrate, poloxamer, povidone, microcrystalline cellulose and a pre-prepared mixture of croscarmellose sodium with dye are mixed until homogeneous, granulated with purified water, dried and the granules obtained are ground. Stearic acid salt is added to the crushed granulate and the finished mass is tabletted. Get tablets with an average weight of 0.100 g (for dosages of 1 mg and 2 mg) and 0.200 g (for dosages of 3 mg and 4 mg), strength 45 ÷ 57 N (for dosages of 1 mg and 2 mg) and 75 ÷ 90 N (for dosages of 3 mg and 4 mg).

The resulting tablets satisfy the regulatory requirements for a pharmaceutical agent. Dissolution,% release of glimepiride into the dissolution medium - phosphate buffer solution with pH = 7.8 - after 15 minutes (HPLC) - 99, the content of glimepiride in one tablet (HPLC) - 1 mg (dosage 1 mg), 2.0 mg ( dosage 2 mg), 3.0 mg (dosage 3 mg) and 4.0 mg (dosage 4 mg). The resulting tablets have a shelf life of more than 2 years.

Other examples are carried out similarly.

Claims (11)

1. The pharmaceutical composition for treating diabetes in the form of a solid dosage form that contains the active substance — glimepiride, disintegrant and other excipients, characterized in that it also includes poloxamer and contains croscarmellose sodium as a disintegrant. 2. The pharmaceutical composition according to claim 1, characterized in that it contains glimepiride, poloxamer and croscarmellose sodium in the following ratio, parts by weight:
Glimepiride one Croscarmellose sodium 0.375-14.0 Poloxamer 0.025-1.5 3. The pharmaceutical composition according to claim 2, characterized in that it contains, as other excipients, lactose monohydrate, microcrystalline cellulose, polyvinylpyrrolidone, a stearic acid salt and a dye. 4. The pharmaceutical composition according to claim 3, characterized in that it contains magnesium stearate as a salt of stearic acid. 5. The pharmaceutical composition according to claim 4, characterized in that it contains iron oxide yellow and / or iron oxide red as a colorant. 6. The pharmaceutical composition according to claim 5, characterized in that it contains ingredients in the following ratio, parts by weight:
Glimepiride one Croscarmellose sodium 0.375-14.0 Poloxamer 0.025-1.5, Povidone (polyvinylpyrrolidone) 0.2-8.0 Lactose Monohydrate 6.5-236.0 Microcrystalline cellulose 1,5-36,0 Stearic acid salt 0.05-12.0 Dye 0.002-0.06 7. The pharmaceutical composition according to claim 6, characterized in that it is made in the form of tablets. 8. The pharmaceutical composition according to claim 7, characterized in that it contains 1 mg glimepiride in one tablet. 9. The pharmaceutical composition according to claim 7, characterized in that it contains 2 mg glimepiride in one tablet. 10. The pharmaceutical composition according to claim 7, characterized in that it contains 3 mg glimepiride in one tablet. 11. The pharmaceutical composition according to claim 7, characterized in that it contains glimepiride in an amount of 4 mg in one tablet.