RU2321405C2 - Drug possessing analgesic, antipyretic and psychostimulating effect and method for its preparing - Google Patents

Abstract

FIELD: medicine, pharmaceutical industry and technology, pharmacy.

SUBSTANCE: invention relates to a method for preparing a drug possessing analgesic, antipyretic and psychostimulating effect. The drug possessing analgesic, antipyretic and psychostimulating effect comprises paracetamol, propiphenazone and anhydrous caffeine as an active components, and starch, microcrystalline cellulose, magnesium stearate, copolyvidon, hydroxypropylmethylcellulose, sodium dodecyl sulfate, crospovidon and croscarmelose sodium as accessory substances taken in the definite ratio of components. Method for preparing a drug possessing analgesic, antipyretic and psychostimulating effect involves stirring sieved powders of paracetamol, propiphenazone, anhydrous caffeine and microcrystalline cellulose followed by wetting the prepared mixture with hydroxypropylcellulose solution and repeat stirring to uniform moisture distribution. Then method involves the successive granulation, drying, powdering prepared granules with a mixture of copolyvidon, dodecyl sodium sulfate, starch, croscarmelose sodium and magnesium stearate to obtain a homogenous mass followed by the tabletting process the prepared homogenous mass. The drug prepared by above described method is made as a tablet and possesses the high dissolving index and the high dosing precision.

EFFECT: improved preparing method of drug.

3 cl, 2 tbl, 1 ex

Description

The invention relates to medicine, in particular to pharmacy, and can be used in the manufacture of solid dosage forms of preparations containing paracetamol, propiphenazone and caffeine as an active principle and having analgesic, antipyretic and psychostimulating effects.

Closest to the proposed is a drug that goes into trade under the name Gevadal® (Gewadal). This product contains the following components: 250 mg paracetamol, 250 mg propiphenazone and 50 mg caffeine. Excipients: microcrystalline cellulose, insoluble polyvinylpyrrolidone, copolyvidone, corn starch, magnesium stearate, talc and highly dispersed silicon dioxide (see http://medi.ru/doc/f7908.htm).

There is also known a method for producing a solid dosage form, which involves mixing the active active principle with auxiliary means, subsequent moistening of the resulting mixture and granulation of the resulting moistened mixture. Then the granulate is dried, dusted and tabletted (see, for example, RU 2190392, publ. 10.10.2002).

The objective of the invention is to obtain a dosage form with storage stability and high therapeutic effect, and the composition of the form must be selected in such a way as to ensure high bioavailability of the active components, the stability of the drug during storage, as well as maximally facilitate the process of serial production of the product.

The technical result of the invention is to provide a high rate of dissolution of the tablets, as well as the high accuracy of their dosage.

The technical result is achieved in that the drug having an analgesic, antipyretic and psychostimulating effect, containing paracetamol, propiphenazone and caffeine anhydrous as the active principle, and starch, microcrystalline cellulose, magnesium stearate and copolyvidone, additionally contains sodium hydroxide as auxiliary substances dodecyl sulfate, crospovidone and sodium croscarmellose in the following components, wt.%:

Paracetamol 9.5-65.5 Propiphenazone 13.8-34.0 Anhydrous caffeine 3,5-8,0 Starch 2.2-7.0 Microcrystalline cellulose 9.5-18.5 Hydroxypropyl methylcellulose 2.5-7.5 Magnesium stearate 0.7-1.5 Copolyvidone 0.1-1.0 Sodium dodecyl sulfate 0.2-1.0 Crospovidone 1.0-7.0 Croscarmellose Sodium 1.0-5.0

The problem is also solved by a method of manufacturing a medicinal product having an analgesic, antipyretic and psychostimulating effect, in accordance with which the sifted powders of paracetamol, propiphenazone, anhydrous caffeine and microcrystalline cellulose are mixed, the resulting mixture is moistened with a hydroxypropylmethyl cellulose solution, re-mixed until a uniform moisture distribution granulation, drying, dry granulation, dusting of the obtained g Anulov kopolividona mixture, sodium dodecyl sulfate, starch, crospovidone, croscarmellose sodium and magnesium stearate to give a uniform mass and pelletizing the homogeneous mass obtained.

The invention consists in the following.

The combination of paracetamol, propiphenazone and caffeine has an analgesic, antipyretic effect. Paracetamol has a predominant effect on the thermoregulation center in the hypothalamus and has a less pronounced ability to inhibit prostaglandin synthesis.

Propiphenazone has an analgesic effect.

Caffeine stimulates the respiratory and vasomotor centers, increases the tone of the vessels of the brain, causes the expansion of the blood vessels of skeletal muscles, heart, kidneys, reduces platelet aggregation. Helps reduce drowsiness, feelings of fatigue, increase mental and physical performance.

The increased effect is achieved by the synergism of two analgesics, in which a small dose of paracetamol significantly increases the bioavailability of propiphenazone. Small doses of analgesics minimize the risk of side effects.

Auxiliary components of this dosage form provide a high release rate of the active components. The use of hydroxypropyl methylcellulose as a binder component improves the technological properties of the tablet mixture, provides flowability sufficient to obtain tablets with minimal weight deviations and, accordingly, dosing, to obtain tablets with high mechanical strength, which accelerates the product packaging process, reduces the exposure time of the production environment per product. At the same time, the quality indicator “description”, which characterizes the appearance, improves. The introduction of croscarmellose (primellose) into the sodium salt provides the necessary speed for the disintegration of high strength tablets.

The invention is as follows.

The sieved powders of paracetamol, propiphenazone, anhydrous caffeine and microcrystalline cellulose are thoroughly mixed, moistened with a hydroxypropyl methylcellulose solution, mixed again until the moisture is evenly distributed and granulated.

The granules are dried, granulated and dusted with a mixture of copolividone, sodium dodecyl sulfate, potato starch, crospovidone, primellose and magnesium stearate, mixed until a homogeneous mass.

The tablet mass is tabletted to obtain oblong-shaped tablets.

Concrete example

Pre-sifted 50.0 kg of paracetamol, 40.2 kg of propiphenazone, 10.0 kg of anhydrous caffeine and 20.02 kg of microcrystalline cellulose are thoroughly mixed and moistened with 25.0% hydroxypropyl cellulose in an amount of 31.0 kg, mixed until uniformly moistened and granulated .

Wet granules are dried at room temperature to a residual moisture of 3-4%

The dried granules are granulated. Dry granulate in the amount of 127.0 kg was dusted by adding pre-sieved copolyvidone 0.508 kg, sodium dodecyl sulfate 0.677 kg, crospovidone 5.08 kg and croscarmellose sodium 3.81 kg. The mixture is stirred until a homogeneous tablet mass is formed.

The mass is tabletted to obtain oblong-shaped tablets weighing 0.75 g in an amount of 125.0 kg.

Table 1 shows the composition 1 obtained in accordance with the example, as well as the compositions of the dosage form with a boundary content of components (2 and 3).

Table 2 shows the test results of the obtained dosage form and its compliance with the requirements of the FSP.

Table 1 Tablet composition The content of components, wt.% one 2 3 Paracetamol (Acetaminophen) 33.33 9.5 65.5 Propiphenazone 28.0 34.0 13.8 Anhydrous caffeine 6.67 8.0 3,5 Potato starch 4.67 7.0 2.2 Microcrystalline cellulose 13.33 18.5 9.5 Hydroxypropyl methylcellulose 5,0 7.5 2.5 Magnesium stearate 1,07 1.5 0.7 Copolyvidone 0.4 1,0 0.1 Sodium dodecyl sulfate 0.53 1,0 0.2 Crospovidone 4.0 7.0 1,0 Croscarmellose Sodium 3.0 5.0 1,0 Characteristics Dissolution%
Paracetamol
Propiphenazone
Caffeine 92-94
90-92
92-94 93-95
90-92
91-93 91-93
91-93
93-95 Deviations of tablets by weight,% ± 0.25 ± 0.25 ± 0.25

From tables 1 and 2 it is seen that the proposed drug in the form of tablets provides a high bioavailability of the active substances, due to their high dissolution, and also has minimal deviations of the tablets by weight, which ensures high metering accuracy.

table 2 Batch number Description Authenticity Average weight, g Dissolution. % Foreign matter Dosing uniformity (caffeine),% Content, g paracetamol propiphenazone caffeine paracetamol propiphenazone caffeine 010903 Creamy white tablets Positive 0.7512 92.2 91.6 92.8 D = 0.04
Three impurities, less than 0.5 each -2.4 to +3.8 0.2487 0.2107 0.0496 020903 Creamy white tablets Positive 0.7495 93.5 91.1 94.2 D = 0.05
Three impurities, less than 0.5 each -2.3 to +3.2 0.2493 0.2094 0.0499 030903 Creamy white tablets Positive 0.7508 92.1 90.3 93.6 D = 0.03
Three impurities, less than 0.5 each -2.6 to +3.3 0.2481 0.2089 0.0492 040903 Creamy white tablets Positive 0.7492 94.3 91.4 92.2 D = 0.05
Three impurities, less than 0.5 each -2.5 to +3.1 0.2495 0.2102 0,0491 050903 Creamy white tablets Positive 0.7504 92.9 90.8 94.1 D = 0.04 -2.7 to +3.6 0.2488 0.2079 0.0497 FSP project requirements White or creamy white tablets, biconvex, oblong in shape with rounded ends HPLC and TLC methods in comparison with RSO or SOVS of paracetamol, propiphenazone and caffeine 0.75 g ± 5% At least 75% in 45 minutes 1. SF method D of the drug solution is not more than 0.19.
2. TLC method. Any impurity no more than 0.5% of the content of the component, in total no more than 1.5 for each component Pass the test 0.238 to 0.263 From 0,200
up to 0.221 From
0.0462 to 0.0538

Claims (2)

1. A medicinal product having analgesic, antipyretic and psychostimulating action, containing paracetamol, propiphenazone and caffeine anhydrous as an active principle, and starch, microcrystalline cellulose, magnesium stearate and copolividone, characterized in that it additionally contains hydroxymethyl cellulose and contains hydroxymethyl cellulose; sodium dodecyl sulfate, crospovidone and sodium croscarmellose in the following components, wt.%: Paracetamol 9.5-65.5 Propiphenazone 13.8-34.0 Anhydrous caffeine 3,5-8,0 Starch 2.2-7.0 Microcrystalline cellulose 9.5-18.5 Hydroxypropyl methylcellulose 2.5-7.5 Magnesium stearate 0.7-1.5 Copolyvidone 0.1-1.0 Sodium dodecyl sulfate 0.2-1.0 Crospovidone 1.0-7.0 Croscarmellose Sodium 1.0-5.0 2. A method of manufacturing a medicine having an analgesic, antipyretic and psychostimulating effect, namely, sifted powders of paracetamol, propiphenazone, anhydrous caffeine and microcrystalline cellulose are mixed, the resulting mixture is moistened with a solution of hydroxypropyl methylcellulose, the mixture is re-mixed until the moisture is uniformly distributed, the moisture is uniformly distributed, the mixture is successively carried out, , drying, dry granulation, dusting the obtained granules with a mixture of copolyvidone, sodium dod ecylsulfate, starch, crospovidone, croscarmellose sodium and magnesium stearate to obtain a homogeneous mass and tableting the resulting homogeneous mass.