Abstract
Introduction. One of the key tasks in freeze‑drying of drug is to choose the optimal cryoprotector that provides a high‑quality lyophilized product.The aim of research. Selection of cryoprotectant and its concentration for the preparation of lyophilizate of the liposomal dosage form of the indolocarbazole derivative LHS‑1269.Materials and methods. Substance LHS‑1269 ≥99 % (N. N. Blokhin National Medical Research Center of Onco logy), egg phosphatidylcholine Е РС S (Lipoid, Germany), cholesterol ≥99 % (Sigma‑Aldrich, Japan), polyethylene glycol‑2000‑distearoyl phosphatidylethanolamine (Lipoid, Germany), mannose‑d (+) 99 % (Kaden, Germany), sucrose (Himmed, Russia), trehalose dihydrate (Himmed, Russia). To obtain LHS‑1269 liposomes, the Bangham method was used in modification for hydrophobic substances with subsequent extrusion of the dispersion of multilayer phos‑ pholipid vesicles. The prepared liposomal dispersion was dosed into vials of 6 ml and lyophilized in the freeze‑dryng chamber using the «step‑by‑step» freezing mode. LHS‑1269 liposomes were analyzed before and after freeze‑drying using laser scattering spectroscopy and determination of the electrophoretic mobility of particles.Results. To prevent the destruction of LHS‑1269 liposomes during lyophilization, substances from the carbohy‑ drates class – mannose, sucrose and trehalose – were studied in two concentrations. In the course of compara‑ tive evaluation of the obtained lyophilizates in terms of quality, appearance, rehydration, size and zeta potential of liposomes before and after sublimation, it was found that sucrose introduced into the liposomal dosage form LHS‑1269 in the molar ratio sucrose / egg phosphatidylcholine 5:1 has optimal cryoprotective properties.Conclusion. As a result of the study, the optimal cryoprotector and its concentration were selected, which ensure the production of high‑quality lyophilizate of the liposomal composition of the indolocarbazole derivative LHS‑1269.
Highlights
To obtain LHS-1269 liposomes, the Bangham method was used in modification for hydrophobic substances with subsequent extrusion of the dispersion of multilayer phos‐ pholipid vesicles
In the course of compara‐ tive evaluation of the obtained lyophilizates in terms of quality, appearance, rehydration, size and zeta potential of liposomes before and after sublimation, it was found that sucrose introduced into the liposomal dosage form LHS-1269 in the molar ratio sucrose / egg phosphatidylcholine 5:1 has optimal cryoprotective properties
As a result of the study, the optimal cryoprotector and its concentration were selected, which ensure the production of high-quality lyophilizate of the liposomal composition of the indolocarbazole derivative LHS-1269
Summary
Выбор КП и его концентрации для получения лиофилизата липосомальной лекар‐ ственной формы производного индолокарбазола ЛХС-1269. Для предотвращения разрушения липосом ЛХС-1269 в процессе лиофилизации исследовали вещества из класса углеводов: маннозу, сахарозу и трегалозу в 2 концентрациях. В ходе сравнительной оценки полученных лиофилизатов по показателям качества − внешний вид, регидратируемость, размер и дзета-потенциал липосом до и после сублимации − установлено, что оптимальными криопротективны‐ ми свойствами обладает сахароза, вводимая в состав липосомальной лекарственной формы ЛХС-1269 в молярном соотношении сахароза / яичный фосфатидилхолин 5:1. В результате проведенного исследования выбран оптимальный КП и его концентрация, обеспечивающие получение качественного лиофилизата липосомальной композиции производного индолокарбазола ЛХС-1269. Выбор криопротектора для получения лиофилизированной липосомальной лекарственной формы производного индолокарбазола ЛХС-1269. Sechenov First Moscow State Medical University, Ministry of Health of Russia; Build 2, 8 Trubetskaya St., Moscow 119991, Russia
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