Razvoj metod za napovedovanje koloidne stabilnosti visokokoncentriranih formulacij z monoklonskimi protitelesi

Müller, Ana (author), Ahlin Grabnar, Pegi (mentor), Bjelošević Žiberna, Maja (co-mentor)

V sklopu magistrske naloge smo z uporabo napovednih parametrov difuzijskega interakcijskega parametra kD in drugega virialnega koeficienta B22 ter tudi preko zeta potenciala sklepali na koloidno stabilnost visokokoncentriranih formulacij z monoklonskimi protitelesi. Ovrednotili smo vpliv sestave formulacije in vpliv kemijske ter temperaturne obremenitve na koloidno stabilnost formulacij z mAb, pri čemer smo le-te izpostavili različnim stresnim pogojem: dodatku vodikovega peroksida, dodatku kislin in/ali baze, dodatku železovih ionov ter povišani temperaturi. Vsi stresni dejavniki so oslabili koloidno stabilnost proteina. Parametra kD in B22 smo ocenili kot ustrezna indikatorja koloidne stabilnosti.

• Language: Slovenian
• Keywords: monoklonska protitelesa, koloidna stabilnost, interakcijski parameter, drugi virialni koeficient, sipanje laserske svetlobe
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-144390
• Publication date in RUL: 18.02.2023

Secondary language

• Language: English
• Title: Development of methods for predicting the colloidal stability of highly concentrated formulations containing monoclonal antibodies

Abstract

We used interaction parameter kD, second virial coefficient B22 and zeta potential to predict the colloidal stability of different high-concentration protein formulations, containing mAbs. We evaluated the influence of chemical and temperature stress on the colloidal stability of mAbs formulations, exposing the formulations to different stress conditions: addition of hydrogen peroxide, addition of acid and/or base, addition of iron ions, and elevated temperature. All stress factors weakened the colloidal stability of the protein. We also evaluated the parameters as suitable indicators of colloidal stability.

• Keywords: monoclonal antibodies, colloidal stability, interaction parameter, second virial coefficient, light scattering