Drug development scale

Desikan, S. Anderson, S.R. Meenan, P.A. Toma, P.H. Crystallization challenges in drug development scale-up from laboratory to pilot plant and beyond. Curr. Opin. Drug Discovery Develop. 2000, 3 (6), 723-733. 

Clinical development continues with the application of the learn-confirm-learn paradigm applied to drug development. Scale up to the first-time-in-human (FTIH) study is best done by the application of sound PM methods as described by several authors (10, 51, 56). 

We have developed the efficient synthesis of the SERM drug candidate 1 and successfully demonstrated the process on a multiple kilogram scale to support the drug development program. A novel sulfoxide-directed borane reduction of vinyl sulfoxides was discovered. The mechanistic details of this novel reaction were explored and a plausible mechanism proposed. The sequence of asymmetric oxidation of vinyl sulfoxides followed by stereospecific borane reduction to make chiral dihydro-1,4-benzoxathiins was applied to the asymmetric synthesis of a number of other dihydro-1,4-benzoxathiins including the sweetening agent 67. 

Schaefer, T., Holm, P., and Kristensen, H. G., Melt Granulation in a Laboratory Scale High Shear Mixer, Drug Development and Industrial Pharmacy, 16(8) 1249-1277 (1990)... 

Examples of PAT applications to drug development are a crystallization process optimization from laboratory to industrial scale [72] optimization of manufacturing steps in pharmaceuticals [70]... 

A simplified view of the pharmaceutical drug development events (not to the time scale) is given in Fig. 1. 

---