[learn_more caption=”Bhavishya Mittal”] Bhavishya Mittal is a Senior Scientist in the Formulation Sciences department at Takeda Pharmaceuticals International Company based in Cambridge, MA. Bhavi has a PhD in Materials Engineering from the Pennsylvania State University and a BS in Chemical Engineering from Regional Engineering College, Jalandhar (India). Bhavi has 12 years of industrial experience in formulation and process development of various solid oral dosages of small therapeutic molecules (oncology, inflammation, and CNS indications) aimed for NDA and ANDA filings. He is the co-chair of the CRO/CMO working group at MassBio. He is the author/co-author of 1 patent application, 10 peer-reviewed manuscripts, and numerous conference papers and posters published/presented in various international journals and conferences. He is an active member of various international professional societies such as AAPS and ISPE. His research interests include formulation design, process engineering, scale-up and tech-transfer, and computational modeling of pharmaceutical unit operations for solid oral dosage manufacturing. [/learn_more]
[learn_more caption=”Sree Haritha Chalasani M.S.”] Sree Haritha Chalasani M.S., is a Sr.Research Associate in the Pharmaceutical Technology, R& D Labs of Takeda Pharmaceuticals International Co. She works on technologies like compaction simulator, spray-drying and modified release. Her main focus is to develop drug product for different stages of clinical trials and transfer the process to manufacturing site. She graduated with a Master of Science in Pharmaceutical Sciences (Drug Delivery Systems) from Northeastern University and a Bachelor of Science (Hons.) from Birla Institute of Technology and Science (BITS), Pilani, India.[/learn_more]
PURPOSE: To evaluate the design space of high shear wet granulation using Huxley Bertram compaction simulator.
METHODS: This was an effort to understand the relationship between the key process parameters (KPP) of HSWG and the critical quality attributes (CQA) of the
tablets made from those granulations.
The KPPs studied for HSWG were spray rate, impeller speed and amount of water added. A full factorial design of experiments (DoE) with these three key process
parameters at two levels and three center points was executed. The formulation was kept the same in all of the experiments. The dried granules were tested for physical properties like bulk/tap density, particle size distribution using Malvern Mastersizer 2000, flowability using Jenike & Johanson ring shear tester, and compressibility using the Huxley Bertram Compaction simulator.
The compressibility of the dried granules was measured by making tablets using a SRC tooling. The simulator was programmed to reproduce a sine wave profile
modeling the SMI Piccola tablet press. The compression sequence was created using a displacement profile to get a compression force in the range of 1‐18KN and the
actual compression force was measured. The profile was run at two turret speeds – 30 and 65rpm. Tablets were made at 4‐5 different compression forces and were
tested for their steady state hardness.
RESULTS: For the same formulation, by changing the process parameters of HSWG, tablets with varied steady state hardness were manufactured. The turret speed didn’t significantly impact the compressibility of any of the granulations.
CONCLUSION: Any differences in the compressibility of the granules produced due to high shear wet granulation process conditions were detected using <3g of each
granulation. We were able to identify the design space of high shear wet granulation using the Huxley Bertram Compaction Simulator.