Abstract
Introduction. An innovative pharmaceutical substance based on the 3,7-diazabicyclo[3.3.1]nonane derivative provides long-term activation of AMPA receptors and the production of neurotrophic factors, which makes it possible to use it for the treatment of cognitive impairments and rehabilitation of patients who have undergone acute brain hypoxia. Given that this substance is able to be absorbed through the walls of the gastrointestinal tract and pass through the blood-brain barrier, there are no restrictions on the development of an oral dosage form. In addition, the oral dosage form has significant advantages when used in geriatric and pediatric practice.Aim. The aim of the work was to carry out a comparative study of the possibility of using gelatin and hypromellose capsules for the development of the composition and technology for obtaining a dosage form containing a pharmaceutical substance based on a 3,7-diazabicyclo[3.3.1]nonane derivative.Materials and methods. The study of the «Dissolution» test of gelatinous and hypromellose capsules was carried out on an ERWEKA DT 720 «Paddle stirrer» apparatus at a stirrer rotation speed of 50 rpm in three media: pH 1.2, pH 4.5 and pH 6.8. The content of the substance in each sample was determined by high performance liquid chromatography with UV detection.Results and discussion. The results of the development and testing of capsules containing an original pharmaceutical substance of nootropic action based on a derivative of 3,7-diazabicyclo[3.3.1]nonane, which has low pharmaceutical and technological characteristics and is practically insoluble in water, are presented. The D/S value was ≥250.00 ml in each physiological pH range. The results of determining the dissolution of the developed dosage form in three media at pH values of 1.2, 4.5 and 6.8 showed a positive effect of the technology used on the solubility of the substance.Conclusion. A significant increase in the solubility of the practically insoluble substance of the 3,7-diazabicyclo[3.3.1]nonane derivative in the developed dosage form was shown, which is the result of the use of a well-founded complex of excipients and the technology of moisture-activated granulation. According to the results obtained, (77.60 ± 2.50) % of the substance passes into the dissolution medium with a pH of 4.5 in 45 minutes. The research results are used to develop a technological scheme for obtaining a finished dosage form, its indicators and quality standards.
Highlights
An innovative pharmaceutical substance based on the 3,7-diazabicyclo[3.3.1]nonane derivative provides long-term activation of AMPA receptors and the production of neurotrophic factors, which makes it possible to use it for the treatment of cognitive impairments and rehabilitation of patients who have undergone acute brain hypoxia
Given that this substance is able to be absorbed through the walls of the gastrointestinal tract and pass through the blood-brain barrier, there are no restrictions on the development of an oral dosage form
The aim of the work was to carry out a comparative study of the possibility of using gelatin and hypromellose capsules for the development of the composition and technology for obtaining a dosage form containing a pharmaceutical substance based on a 3,7-diazabicyclo[3.3.1]nonane derivative
Summary
Фармацевтическая субстанция на основе производного 3,7-диазабицикло[3.3.1]нонана с химическим названием IUPAC 6-[4метокси-3-(1Н-пиразол-1-илметил) бензил]-1,11диметил-3,6,9-триазатрицикло[7.3.1.1] тетрадекан-4,8,12-триона была впервые синтезирована на химическом факультете МГУ им. Ломоносова [1] (рисунок 1). Структурная формула 6-[4-метокси-3-(1H-пираз о л -1- илметил) бензил] -1,11- диметил -3 , 6 , 9 - триазатрицик ло[7.3.1.1] тетрадекан-4,8,12-трион Figure 1. ФС ТСТ-9 представляет собой белый аморфный порошок без запаха. Определение биофармацевтической растворимости ФС ТСТ-9 проводили методом встряхивания в термостатируемой колбе. Полученные данные по растворению позволяют отнести субстанцию к ΙΙ/ΙV классу по Биофармацевтической классификационной системе. Усредненные результаты определения технологических характеристик порошка ФС ТСТ-9, полученные в результате измерений 6 образцов, приведены в таблице 1. Полученные результаты свидетельствовали о низких технологических свойствах субстанции (сыпучесть, угол откоса, насыпная плотность). На основании рассчитанных величин индексов Карра и Хауснера сыпучесть субстанции была оценена как «очень плохая».
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