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
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)
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
Dissolution Analysis
- 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.