ФАРМАЦЕВТИЧЕСКАЯ РАЗРАБОТКА КОМБИНИРОВАННОГО ПРЕПАРАТА МЕМАНТИНА И ЦИТИКОЛИНА С МОДИФИЦИРОВАННЫМ ВЫСВОБОЖДЕНИЕМ: ИССЛЕДОВАНИЯ ТЕХНОЛОГИЧЕСКИХ СВОЙСТВ СУБСТАНЦИЙ

Abstract

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.