The study of liophilization parameters in the liposomal irinotecan development




liposomes, chemical gradient, high pressure extrusion, cryoprotector, freeze drying


The creation of the liposomal irinotecan is one of the main ways to reduce toxicity and increase the effectiveness of chemotherapy. Lyophilization makes it possible to obtain a product with a guaranteed stability of the size and encapsulation efficiency.

Aim. To optimize the content of the cryoprotector in the liposomal irinotecan, and develop lyophilization parameters to produce liposomes with the maximum encapsulation of irinotecan in them, alongside while maintaining the nanosize.

Materials and methods. Egg phosphatidylcholine from Lipoid (Germany) was used for preparation of liposomes. Lyophilization was carried out in a Quarco device (PR China). The encapsulation degree was determined on a Shimadzu LC-20 instrument (Japan) by HPLC method developed earlier.

Results and discussion. The optimal content of the cryoprotector – trehalose dihydrate has been studied. It has been found that the optimal content of trehalose dihydrate is 8 % (w/w). The modes of the product lyophilization have been studied. The secondary drying temperature in the range of 10-20 °C has been determined. At the secondary drying temperature of 10 °C the residual moisture content was 5-8 %, which was beyond the target range. At 20 °C the water content in the lyophilizate was 0.5-0.8 %, the loss of encapsulation was up to 20 %. The mode of drying at 15 °C was optimal, while the residual water content in the lyophilizate was 1.5-2.8 %, the loss of encapsulation was 13 %, the size of the liposomes after lyophilization and rehydration did not change significantly compared to the initial one.

Conclusions. As a result of the studies, liposomes with irinotecan have been obtained. The content of trehalose dihydrate as a cryoprotector in the range of 4-10 % has been studied. It has been shown that the optimum content of trehalose dihydrate is 8 % (w/w); moreover, the encapsulation decrease in lyophilization is 13 %. The modes of the liposomal irinotecan lyophilization have been studied at the final drying temperature of 10, 15 and 20 °C. It has been found that the optimum final drying temperature is 15 °C.

Author Biographies

O. V. Stadnichenko, National University of Pharmacy

Candidate of Pharmacy (Ph. D.), external PhD student of the Drug Technology Department

Yu. M. Krasnopolsky, National Technical University “Kharkiv Polytechnic Institute”

Doctor of Pharmacy (Dr. habil.), professor

T. G. Yarnykh, National University of Pharmacy

Doctor of Pharmacy (Dr. habil.), professor, head of the Drug Technology Department


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Technology of Medicines