PHARMACEUTICAL DEVELOPMENT OF A FIXED DOSE COMBINATION FORM OF MEMANTINE AND CYTICOLINE WITH MODIFIED RELEASE: RESEARCH OF TECHNOLOGICAL PROPERTIES OF SUBSTANCES

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2021-23-7-68-73 ◽

2021 ◽

pp. 68-73

Author(s):

Salakhetdinov D.K. ◽

Sysuev B.B.

Keyword(s):

Bulk Density ◽

Fixed Dose Combination ◽

Fixed Dose ◽

Modified Release ◽

Technological Properties ◽

Pharmaceutical Development ◽

Pharmaceutical Substances ◽

Monosodium Salt ◽

Dose Combination ◽

Tablet Compression

The pharmaceutical development of a fixed dose combination form of citicoline and memantine for the treatment of cognitive disorders, which will improve compliance is a topical area of research. Purpose: to investigate the technological properties of the active pharmaceutical ingredients: memantine hydrochloride and citicoline monosodium salt in the framework of the development of a fixed dose combination modified release. The samples of pharmaceutical substances citicoline "Kyowa Hakko Bio Co., Ltd." (Japan) and memantine hydrochloride - Hetero Drags Limited (India) were used. Technological studies of the substances were carried out in accordance with the requirements of the State Pharmacopoeia of the RF XIV edition. It was revealed that the particles of the investigated substances show an anisodiametric shape, the anisodiametric shape of the analyzed particles indicates possible poor flowability of APIs, which predicts difficulties in dosing during the tablet compression process. The following characteristics were studied: the ability of the powder to compaction, the bulk density and compressibility index, Hausner ratio were established. It was found that, according to the USP classification, the flowability of substances can be characterized as very, very poor. Pharmaceutical substances of memantine hydrochloride and citicoline monosodium salt have unsatisfactory technological properties, which can complicate the processes of die filling and dosing of pharmaceutical substances during tableting tablet compression. To prevent these disadvantages, it is further recommended to provide research on the possibility of using wet granulation, or the usage in the composition of the tablet mass of excipients with a high bulk density and good flowability. Thus, within the framework of pharmaceutical development, the physicochemical properties of the pharmaceutical substances memantine hydrochloride and citicoline monosodium salt were investigated.

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RESEARCH OF ACUTE TOXICITY OF FIXED DOSE COMBINATION TABLETS OF CITICOLINE AND MEMANTINE

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2021-23-7-49-54 ◽

2021 ◽

pp. 49-54

Author(s):

Salakhetdinov D.K. ◽

Sysuev B.B.

Keyword(s):

Acute Toxicity ◽

Clinical Signs ◽

Fixed Dose Combination ◽

Fixed Dose ◽

Intragastric Administration ◽

Test Drug ◽

Modified Release ◽

Dose Combination ◽

Males And Females

The development and study of the fixed dose combination tablets of citicoline and memantine is the relevant problem. The purpose of this study was the assessment of acute toxicity and local irritating effect of the new combined drug, the modified release tablets (citicoline 500 mg + memantine 10 mg). Material of research: fixed dose combination of modified release tablets (citicoline 500 mg + memantine 10 mg) (NovaMedica Innotech, Russia). The tested drug was administered intragastrically to males and females of half-plant outbred rats at a dose of 2000 mg/kg in the amount of active substances. According the research results, the death of animals was not noted. As it was found the value of LD50 for the test drug in the intragastric administration is>5000 mg/kg in accordance with OECD Test No.423. The tested drug can be attributed to the 5th grade of toxicity on the international classification of GHS, because LD50> 5000 mg/kg (V/g) and to 4 class of low-toxic compounds as per Hodge and Sterner classification: 500 <d50 ≤ 5000 mg/kg (V/g). No clinical signs of intoxication in males and females of autumn rats against the background of a single intragastric administration of the test drug was detected visually, There were no changes in animals behavior in the direction of oppression or excitement. The test drug in a single intragastric introduction in a dose of 2000 mg/kg in the amount of active ingredients did not cause a local irritant action. Thus, the drug does not have a toxic and local irritating action in one-time introduction.

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