Abstract

FORMULATION DESIGN AND DEVELOPMENT OF LYOPHILZATION CYCLES FOR NOVEL FORMULATION OF PROTEASOME INHIBITOR: BORTEZOMIB

Yaswanth Allamneni*, T.E.G.K Murthy, Mandava Venkata Basaveswara Rao, Y. Udaya Bhaskara Rao

ABSTRACT

is a proteasome inhibitor which acts by binding with the catalytic site of 26s proteasome which leads into arresting of cell cycle. Developing the novel stable lyophilized dosage form over the brand product is the major objective of our study and the main focus is minimize the total drying time without impacting the quality of the drug product. Suitable solvent system and the excipients for the lyophilization process were selected based on the past knowledge in the pre-formulation study of the selected drug candidate. Critical collapse temperature for bortezomib in the selected solvent system was determined and the value was found to be -22°C. Based on the critical temperature, majority of the time the product was sublimated at -30°C
for better drying efficiency during primary drying stage. Description, assay, related substances, reconstitution time, residual solvents, pH of the reconstituted solution were identified as the CQA’s (Critical quality attributes) for the drug product during the optimization of lyophilization cycles and they met the QTTP (Quality target product profile) with respect to the brand product. Further the final optimized formulation was subjected for stability studies.

Keywords: proteasome inhibitor, critical collapse temperature, pre-formulation study, critical quality attributes and quality target product profile.