USE OF POLYETHYLENE GLYCOL IN FREEZE-DRYING TECHNOLOGY FOR PREPARATION OF A GC-2-BASED SOLUTION FOR INJECTION

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DOI: https://doi.org/10.29296/25419218-2018-06-05
Issue: 
6
Year: 
2018

E.V. Blynskaya(1), S.V. Tishkov(1), K.V. Alekseev(1), S.V. Minaev(1), A.I. Marakhova(2) 1-V.V. Zakusov Research Institute of Pharmacology, 8, Baltiyskaya St., Moscow 125315, Russian Federation; 2-Peoples’ Friendship University of Russia, 6, Miklukho-Maklai St., Moscow 117198, Russian Federation

Introduction. The low-molecular-weight nerve growth factor (NGF) loop 4 dipeptide mimetic bis-(N-monosuccinyl-L-glutamyl-L-lysine) hexamethylene diamide that received a working GK-2 code was designed under the supervision of T.A. Gudasheva at the Department of Drug Chemistry, V.V. Zakusov Research Institute of Pharmacology. The compound showed neuroprotective activity in in vitro experiments. Objective: to investigate the possibilities of using polyethylene glycol (PEG) in combination with cryo- and lyoprotectants to prepare a drug based on the original pharmaceutical substance GK-2 to be used as a lyophilisate for injection,. Material and methods. The substance GK-2 obtained at the V.V. Zakusov Research Institute of Pharmacology and excipients, such as the lyoprotectant sucrose and the cryoprotectants PEG 1500, 4000, and 6000, were applied. Two types of freezing (slow and fast) were performed. Harrington’s mathematical desirability function was used for the statistical processing of the results. Results. Medium-molecular-weight polyethylene glycols used as cryoprotectants in freeze-drying technology were substantiated and applied; the ratios of excipients were selected. The eutectic temperature and quality indicators (transparency, dissolution time, pH level, and residual moisture) of the obtained lyophilisates were determined for each composition. The freeze-drying temperature curves that met most the requirements for compositions were constructed; and the model structure with optimal technological freeze-drying modes was selected. Conclusion. Lyoprotectants and cryoprotectants should be used in the freeze-drying of the peptide substance GK-2. The application of PEG of different molecular weights in freeze-drying technology was assessed. Harrington’s generalized desirability function was used to substantiate the substance GK-2-based drug composition that is in compliance with the requirements of the Pharmacopoeia of the Russian Federation, 13th edition [4].
Keywords: 
lyophilisate for preparation of solution for injection
GK-2
neuroprotective activity
Harrington’s generalized desirability function
cryoprotectant
lyoprotectant
medium-molecular-weight polyethylene glycols
References: 
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