Features pharmaceutical development lyophilisate GK-2 for parenteral use

Abstract

Introduction. The section «Pharmaceutical development» is an integral part of the registration dossier when developing a dosage form, however, this process is of particular importance for lyophilized dosage forms (LF), due to the sensitivity of lyophilization to the slightest changes in temperature, pressure and other factors. The purpose of this work is to demonstrate the capabilities of the methods shown in ICHQ8 Pharmaceutical Development, ICH Q9 Quality Risk Management and Guidelines for the Development and Production of a Drug Product (Pharmaceutical Development) (EurAsEC).

Materials and methods. These methods are used in the development of a LF for parenteral use based on the original pharmaceutical substance hexamethylene amide bis- (N-monosuccinyl-L-glutamyl-L-lysine) GK-2, which has neuroprotective activity. The studies were carried out using the substance GK-2, and as excipients: lyoprotectant – sucrose, cryoprotectants – medium chain polyethylene glycols 1500, 4000, 6000.

Results. The risks arising during the production of LF of a lyophilisate for parenteral use are estimated on the basis of a cause and effect diagram (Ishikawa diagram). Based on the chart, identified the main factors affecting the quality of the final product. Also, the critical
parameters of the processes, critical control points and interrelated critical parameters of quality, model compositions of the lyophilisate GK-2 for parenteral use were analyzed.

Conclusion. According to the data obtained, a model composition has been proposed, which has shown the optimal technological and biopharmaceutical properties and the technological scheme of its production.