From Lab Formulation Development to CTM Manufacturing of KO-947 Injectable Drug Products: a Case Study and Lessons Learned

Formulation development of KO-947-K mesylate injectable drug products was described. Solution formulations were initially attempted, and key parameters such as drug concentration, buffer, pH, complexing agent, and tonicity modifying agent were carefully evaluated in the lab setting, mainly focusing...

Full description

Saved in:
Bibliographic Details
Published in:AAPS PharmSciTech 2021-07, Vol.22 (5), p.168-168, Article 168
Main Authors: Deng, Xiaohu, Ren, Pingda, Mai, Wanping, Wang, Yi, Zhang, Yuanyang, Wu, Hongbing, Xie, Yinwei, Chen, Huazhen
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Pharmacology/Toxicology
Pharmacy
Research Article
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Formulation development of KO-947-K mesylate injectable drug products was described. Solution formulations were initially attempted, and key parameters such as drug concentration, buffer, pH, complexing agent, and tonicity modifying agent were carefully evaluated in the lab setting, mainly focusing on solubility and chemical stability. A lead solution formulation was advanced to a scaleup campaign. An unexpected stability issue was encountered, and the root cause was attributed to the heterogeneous liquid freezing process of the formulated solution at −20°C, which had not been captured in the lab setting. A lyophilized product was then designed to overcome the issue and supplied to the phase I clinical trial. Graphical abstract
ISSN:1530-9932
1530-9932
DOI:10.1208/s12249-021-02059-x