Investigation of Bortezomib stability in the presence of polyol excipients

Abstract

Introduction: anticancer drugs, in general, have less specialty compared to other drugs, hence they have more side effects compared to other drugs. Meanwhile, anti-cancer drugs with more specialty (e.g. Bortezomib) are more accepted than other ones. Bortezomib is sensitive to light, temperature, hydrogen peroxide and acid due to its chemical structure, having boron atom and its related hydroxyl groups. Results of the studies have shown that Bortezomib drug formulations, which include polyols are more stable than drug pure powder due to formation of polyols complex. Objectives: the aim of the present study was investigation of physical stability of Bortezomib at the presence of various polyols. Methods and materials: In this study, lyophilized formulation of polyols drug complexes were prepared using mannitol, dextrose, dextran and alpha- cyclodextrin polyols. Moreover, a non-polyols polymer (PVPK30) was used as a negative controller. The prepared formulations were kept under different temperature and humidity conditions, and then samples were taken at different time intervals, being analyzed by HPLC. Findings: Findings of the study indicated that remaining Bortezomib percent at the presence of mannitol polyols and cyclodextrin was 95.1% and 94.3%, respectively. This shows that the drug was in stable formulation, but Bortezomib products have drug remnant of less than 90% at the presence of dextrose, dextran polyols and non-poly polymer (PVPK30), so that at the end of month 6, drug remnant percent of dextrose, dextran and PVP were 89%, 82.5% and 67.4%, respectively. Moreover, drug remnant percent of all polyol drug products solution was more than 98% during 8 hours. This shows the formulation stability at solution state. Conclusion: Mannitol and Cyclodextrin polyols resulted in increased Bortezomib stability due to having hydroxyl groups at their structure and formation of drug-polyols complex.