The Concept “Quality by Design” in development of Liposomal cytostatics

Abstract

The purpose of this paper is an analysis of technology for obtaining liposomal cytostatics from the point of view of the Quality by Design approach. Liposomes were manufactured by a lipid film with further high-pressure extrusion method. Number of critical stages of technology that are necessary for the study have been circled during the pharmaceutical development. Optimization of the intraliposomal pH was demonstrated by the example of obtaining the liposomal doxorubicin hydrochloride. The study of the high pressure extrusion parameters was carried out in the development of the liposomal oxaliplatin technology. An optimization of lipid bilayer composition is shown for liposomal irinotecan. It was shown that the optimal pH value for the liposomal form of doxorubicin hydrochloride was at 3 ± 0.5. The optimal composition of the lipid bilayer for the liposomal form of irinotecan is the Egg phosphatidylcholine/Cholesterol ratio, 80/20% (wt.). Which provides a liposome size of 108 ± 3.1, and the degree of encapsulation of irinotecan hydrochloride into liposomes was 87 ± 0.8%. The oxidation index was studied on model samples of liposomal forms of irinotecan hydrochloride (Io = 0.372) and oxaliplatin (Io = 0.323).