KinetiSol Processing for Amorphous Vemurafenib Compositions

Summary
  • KinetiSol processed VEM:HPMCAS-L (3:7) achieved key quality targets establishing equivalency to MBP
  • KinetiSol was demonstrated to be a feasible manufacturing technology for the production of amorphous dispersions of vemurafenib
  • KinetiSol should be considered as an alternative to MBP for the production of amorphous dispersions with challenging compounds
  • Several opportunities for vemurafenib formulation enhancement by KinetiSol given the expanded formulation space relative to MBP

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Zelboraf Manufacturing Process
ZelborafTM Drug Product Manufacturing
1. API manufacture
2. MBP: Amorphous API in HPMCAS (3:7)
3. Roller compaction
4. Tablet compression
5. Tablet compression

Shah et al. JPharmSci. Vol. 102, 697 – 981 (2013)

Shah et al. JPharmSci. Vol. 102, 697 – 981 (2013)

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Vemurafenib: Why KinetiSol?
  • Melt extrusion not feasible
    • Very high melting point API: 272 °C
    • High drug loading: 30% w/w
    • Thermally sensitive polymer: HPMCAS
  • Spray drying not feasible – poorly soluble in low & moderate boiling temp organic solvents
  • MBP process is complex, costly and inefficient
  • MBP not available in developing markets

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Dissolution Analysis

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  • Extensive supersaturation similar to MBP
  • Slower rate of release due to greater density of KSD amorphous intermediate
  • MBP requires roller compaction prior to tableting; KinetiSol AI does not

CASE STUDIES

Read about exciting new breakthroughs

KinetiSol® has been the subject of numerous research articles published in top peer-reviewed journals in recent years. These papers demonstrate unique capabilities of the KinetiSol®process and its benefits for amorphous solid dispersion processing. Key advantages of the KinetiSol® process are illustrated in these case studies.

 

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