The Challenge
A small US-based biopharmaceutical company has selected TEDOR to manufacture their
first oral solid dose product for clinical trials.
Following the successful completion of their Phase I clinical trial, the company decided
to change the API manufacturing site and process. This was done to reduce API
impurities, which has led to differences in physical properties of the API. During R&D
trials with the new API, the tablets showed lamination and capping with the new
formula as compared to the previous formulation, which could be compressed using
direct compression.
The Solution
Our teams ran several experiments to see if a change in excipients level or grade could
resolve the issue; the formulation was already dosed for Phase I clinical study and the
customer did not want to change the formulation significantly. However, with the major
component of the formulation being the API (50%), the issue could not be resolved using
the direct compression approach.
It was decided to evaluate non-aqueous wet granulation, adding a small level of a binder
while keeping the formulation excipients and their level similar. This non-aqueous wet
granulation resulted in an acceptable formulation.
Compaction was also evaluated as an alternate approach, which we explored to avoid
the addition of a new excipient. The amount of API was limited, therefore a slugging
trial on a compression machine was evaluated instead of roller compaction. A successful
formulation was also achieved with this slugging trial, which also meant there was no
need to add a new excipient.
The Outcome These two alternative solutions have been provided to the customer, both the nonaqueous
wet granulation approach and the slugging approach (via roller compaction).
The ultimate decision on the formulation will be finalized based on an evaluation from
the customer and a phase IB clinical batch that will be manufactured.