Abstract
Objective: Development of a lyophilized injectable dosage form LCS-1208, an original antitumor drug based on an indolocarbazole derivative.
 Methods: The prepared solution of the injectable dosage form LCS-1208 is transferred to sterilizing filtration, which is carried out under vacuum on a «Stericup» filter unit with a filter pore size of 0.22 μm. The sterile solution of the injectable dosage form LCS-1208 is poured into sterile vials using a dispenser and lyophilized in a freeze-drying chamber. At the end of drying, the preparation is corked in the chamber of a sublimation unit using a hydraulic device and transferred to crimping with aluminum caps using a seaming machine. Quantitative determination of the drug content was determined by spectrophotometry using a standard sample at λ = 320±2 nm. The pH was determined by potentiometry.
 Results: A freeze-drying regimen for the injectable dosage form LCS-1208 has been developed. The required solution freezing temperature was established taking into account the presence of 2 eutectic zones: a solution of LCS-1208 in DMSO (-35 ÷-32) °С, an aqueous solution of Kollidon 17PF (-10 ÷-8) °С. As a result of a series of experiments, the optimal lyophilization regime was chosen that does not require preliminary freezing in a low-temperature chamber, with freezing on the shelves of freeze-drying at a temperature of-47 °C without their preliminary cooling. The most acceptable vial filling volume was determined, amounting to 3 ml, and the rate of temperature rise during secondary drying of the preparation was justified. When using the developed regime of lyophilization of the LCS-1208 solution, it was shown that it can be sublimated while preserving the initial qualitative and quantitative characteristics.
 Conclusion: In this article, using the example of creating a lyophilized injectable dosage form LCS-1208 (the original antitumor drug from the indolocarbazole group), the main problems that arose during the lyophilization of the selected composition of the model solution, as well as ways to improve the process.
Highlights
Lyophilization is a process that has frequent problems at the stage of development and production of the dosage form; risks at control points are especially numerous
The main ways to improve the lyophilization process is to optimize the technological aspects of drying and directly select auxiliary substances, based on the physicochemical basis of the process [1,2,3]. These approaches are considered by the example of the development of a lyophilized injection dosage form (ILF-lyo) LCS-1208, an original antitumor drug based on an indolocarbazole derivative [4]
The aim of this study was the development of a lyophilized injectable dosage form LCS-1208, an original antitumor drug based on an indolocarbazole derivative
Summary
Lyophilization is a process that has frequent problems at the stage of development and production of the dosage form; risks at control points are especially numerous. The main ways to improve the lyophilization process is to optimize the technological aspects of drying and directly select auxiliary substances, based on the physicochemical basis of the process [1,2,3] These approaches are considered by the example of the development of a lyophilized injection dosage form (ILF-lyo) LCS-1208, an original antitumor drug based on an indolocarbazole derivative [4]. If the contents of the operating substance are small or significant, the subject of lyophilization is, it is small in water or water-alcohol mixture, a dosage form is introduced into the composition of the dosage form filler In quality of such fillings, most often use high molecular weight compounds, polyvinylpyrrolidone (PVP) [5]; carbohydrates–sucrose, lactose; carbohydrate-containing alcohols– mannitol, sorbitol; glycine and others
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