Изучение факторов, влияющих на стабильность липосом с цитостатиками при регидратации

Abstract

Oxaliplatin and irinotecan are prospective active pharmaceutical ingredients (API) for liposomal form creation. Development with the final lyophilization was carried out to improve stability of the eventual dosage forms. It is necessary to provide essential stability of colloidal formulations after rehydration, for the successful application of liposome preparations in therapeutic practice. The stability parameters involves such criteria, as encapsulation degree and liposomes size, as well as the thermodynamic stability of the whole colloidal system. The effect of cholesterol on the liposomes size and the encapsulation degree after rehydratation, with liposomal irinotecan as example, was studied. Liposomes were obtained by “chemical gradient”, with sodium citrate as the internal buffer solution. It was shown that cholesterol improves the stability of size and encapsulation degree, the optimum content was 20% by weight. The influence of the zeta potential on the thermodynamic stability of the liposomes after rehydration was also studied with liposomal irinotecan and liposomal oxaliplatin as examples. Increased stability of irinotecan liposomes was achieved with the addition of l-lysine (concentration 0.012%), the value of the zeta potential was -5,1 mV.