UA140829U - COMBINED MEDICINE OF ANALGESIC, ANTI-INFLAMMATORY AND ANTHYDRATING ACTION - Google Patents

Abstract

Combined drug of analgesic, anti-inflammatory and antipyretic action, containing paracetamol, caffeine, acetylsalicylic acid, as excipients contains as a disintegrant - hydroxypropylcellulose low-substituted, as a filler and a binder as a cellulose-containing cellulose substances are additionally introduced as a binder - gelatinized starch, as an inhibitor of hydrolysis of acetylsalicylic acid - anhydrous citric acid, microcrystalline cellulose selected with a low moisture content.

Description

The useful model belongs to medicine, pharmacology and can be used in the pharmaceutical industry in the manufacture of a combined medicinal product with analgesic, anti-inflammatory and antipyretic action, containing acetylsalicylic acid, paracetamol, caffeine and can be prescribed in the treatment of mild or moderate pain syndrome: in headache or toothache pain, with primary dysmenorrhea, migraine, arthralgia, neuralgia, diseases accompanied by hyperthermia of various etiologies (as an antipyretic).

The known composition of the medicinal product contains acetylsalicylic acid, paracetamol, caffeine and auxiliary substances: low-substituted hydroxypropyl duocellulose, microcrystalline cellulose, stearic acid, hypromellose, titanium dioxide, propylene glycol, benzoic acid, carnauba wax. The disadvantage of the composition of the well-known medicine is the multicomponent composition of auxiliary substances (pirz:/Larieiki.sna/lyk/Zksedrin/).

The basis of a useful model is the task of improving the composition, namely achieving the minimum impact on the active substances of negative technological factors: the effect of high temperature, moisture. As a result of the conducted research, it was possible to obtain a stable composition that has the necessary chemical and technological characteristics.

The task is solved by the fact that the combined drug with analgesic, anti-inflammatory and antipyretic action contains paracetamol, caffeine, acetylsalicylic acid, as auxiliary substances it contains low-substituted hydroxypropyl cellulose, microcrystalline cellulose, stearic acid, according to the useful model, as auxiliary substances anhydrous citric acid is additionally introduced. gelatinized starch, microcrystalline cellulose (with low moisture content).

At the same time, the combined medicinal product contains the following ratio of components by weight. 9o: paracetamol 33-35 caffeine 8.5-9.3 acetylsalicylic acid 33-35 low-substituted hydroxypropyl cellulose 3-4 microcrystalline cellulose 2-3 progelatinized starch, 12.5-18.5 citric acid 0.5-1.5 stearic acid 1.5-2.5.

The composition of the drug is a compromise between the need to have a strong tablet and the impossibility of using them in a sufficiently large amount, taking into account the hydrolysis of acetylsalicylic acid.

When developing the composition and technology, the emphasis was placed on the technological aspect of obtaining a tableting mass, in which acetylsalicylic acid was added to the tableting mass

Zo after receiving granules from paracetamol and caffeine. Thus, the hydrolyzable component excluded contact with the humectant containing water and temperature exposure. This approach significantly improves the stability of the finished medicinal product.

When choosing excipients and their quantity, their influence on the mechanical stability of the finished dosage form and the achievement of the required dissolution were taken into account. The selected excipients also allowed solving technological issues, such as the flowability of acetylsalicylic acid, adhesion of the tableting mass to the pre-instrument, and low compressibility.

The following was taken into account from the literature:

This combination does not have good stability, i.e. amino groups of paracetamol and caffeine enhance the hydrolysis of acetylsalicylic acid.

The rate of decomposition of acetylsalicylic acid depends on the amount of excipients included in the tablet, which in turn corresponds to the total moisture content.

The stability of acetylsalicylic acid is also affected by the nature of excipients, the presence of amino groups and metal ions in them, which in turn negatively affects the stability of the finished dosage form.

The primary packaging of the finished dosage form also plays an important role.

In order to obtain the optimal quality of the drug according to technological indicators, the method of wet granulation was chosen, i.e. a relatively large amount of paracetamol and caffeine in the tablet (40 95) and their fluidity is absent. This leads to the need to granulate them with a solution of a binder followed by drying and dry calibration to obtain granules with the necessary technological properties (size, flowability, compressibility).

The ratio of microcrystalline cellulose (with low moisture content), pregelatinized starch, and low-substituted hydroxypropyl cellulose was selected to achieve the required strength and disintegration time of the tablets as a binder. Also, microcrystalline cellulose (with low moisture content), hydroxypropyl cellulose, and pregelatinized starch are among the more compatible excipients of acetylsalicylic acid due to their low free water content and chemical inertness.

Stearic acid was used as a lubricant, i.e. it does not contain metal ions and provides a satisfactory level of lubrication of punches during tableting.

The method is specifically carried out as follows.

Purified water is loaded into the reactor for the preparation and supply of granulating solutions, the mixing device is turned on, and 9.21 kg of pregelatinized starch is loaded.

Mix until the moisturizer is completely homogeneous.

170.17 kg of paracetamol, 44.24 kg of caffeine, 25.78 kg of gelatinized starch, 8.57 kg of low-substituted hydroxypropyl cellulose are loaded into the mixer-granulator and mixed. Then, a wetting agent - a suspension of gelatinized starch - is added in portions to the mixer-granulator and mixing is prolonged until the wetting agent is evenly distributed in the mass. The wet mass is calibrated everywhere on the grid with the determined diameter of the holes. The resulting mass is dried in a fluidized bed drying unit at a given temperature to a given humidity. The dry mass is calibrated on a calibrator with a given hole diameter. A calibrated mass, 12.24 kg of microcrystalline cellulose, 26.4 kg of gelatinized starch, 8.58 kg of low-substituted hydroxypropyl cellulose, 4.9 kg of anhydrous citric acid, and 170.14 kg of acetylsalicylic acid are loaded into the mixer for dry mixing and mixed. Then add 9.8 kg of stearic acid and continue mixing. The mass should be homogeneous. At the end of powdering, the mass is transferred to tableting.

Oblong tablets with a biconvex surface with CM embossed on one side, white or almost white in color are obtained. Shades of gray color are allowed.

Table 1 - . The number of

Name of the component Function of the GLS component. o "o

Acetylsalicylic acid 33-35

Paracetamol 33-35

Caffeine 8.5-9.3

Microcrystalline cellulose Dry binder

Microcrystalline cellulose. Dry binder with low moisture content 3-20

Pregelatinized starch Multifunctional substance

Hydroxypropyl cellulose: . - Disintegrant, anti-camping substance low substituted 1-4.0

Hydroxypropyl cellulose. low molecular weight Binder (in solution) 0 5-2 5

Anhydrous citric acid Inhibitor of hydrolysis of acetylsalicylic acid 0.5-1.5

Citric acid monohydrate Inhibitor of hydrolysis of acetylsalicylic acid 0.5-1.0

Calcium stearate Binder up to 1.0

Magnesium stearate Binder up to 1.0

Crospovidone XI -10, XI. Disintegrant 1.0-3.0

Povidone K-25 Binder (in solution) 0.5-4.0

Lead on K-17 Binder (in solution) 0.5-4.0

Colloidal silicon dioxide Binder, water-repellent hydrophobic 2972 Rpagta agent 1.0-2.0

Colloidal silicon dioxide d d d d Lubricant anhydrous 1.0-2.0

Talc Lubricant 1.0-3.0

Hydroxypropylmethylcellulose Binder (in solution) 0.5-1.0

Potato starch Filler 10.0-20.0

Croscarmellose sodium Ready film-forming mixture 1.0-3.0

Coo)

Continuation of table 1

As a result of the selection of the composition, the components presented in Table 1 in various combinations and quantities were used. For GLZ3, the stability in different primary packages was studied. As a result, it was established that the composition indicated in Table 2 has more acceptable technological characteristics of the mass for tableting (bulk density, flowability) and pharmacological and technological characteristics of tablets - acceptable strength, ability to wear and disintegrate, and also has a stable profile of the release of active substances , and stability during the specified shelf life of the finished product in a blister made of laminated polyvinyl chloride film. IN

Table 2 presents the composition of the claimed drug.

Table 2

The composition of the claimed preparation, the tablet of the medicinal product, the substance) Palia 2 34.72 |API 100 95 dry substance) acetylsalicylic acid

As a result of pharmaceutical development, the optimal composition of the medicinal product was selected, which has the necessary pharmaco-technological characteristics of the mass for tableting and the finished product, with the best form for convenient swallowing by the patient; proven compatibility of active pharmaceutical ingredients and auxiliary substances included in the composition of the finished product by studying the stability of GLZ at the specified expiration date; the dissolution profiles of different series of the finished drug were investigated and the reproduction of the technological process and the quality of the drug from series to series in production were confirmed;

Thus, the proposed composition and the technology of obtaining the drug in the form of a tablet are optimal and technological during production, as well as auxiliary substances and provide the necessary pharmaco-technological indicators of the quality of the finished dosage form, its stability during the stated shelf life.

Claims (2)

USEFUL MODEL FORMULA 1. Combined medicinal product with analgesic, anti-inflammatory and antipyretic effect, containing paracetamol, caffeine, acetylsalicylic acid, as auxiliary substances, contains as a disintegrant - low-substituted hydroxypropyl cellulose, as a filler and binder - microcrystalline cellulose, as a lubricant - stearic acid, which differs in that, as auxiliary substances, additionally introduced as a binder - progelatinized starch, as an inhibitor of the hydrolysis of acetylsalicylic acid - anhydrous citric acid, microcrystalline cellulose selected with a low moisture content. 2. The combined drug according to claim 1, which differs in that it has the following ratio of components, wt. for: paracetamol 33-35 caffeine 8.5-9.3 acetylsalicylic acid 33-35 low-substituted hydroxypropyl cellulose 3-4 microcrystalline cellulose with 2-3 low moisture content gelatinized starch 12.5-13.5 anhydrous citric acid 0.5-1 .5 stearic acid 1.5-2.5.