Case study II
Optimisation of a Phase II Formulation
Objectives and Key Challenges
This case study involved a customer project where the objective was to optimise a formulation of their NCE and produce pilot batches of finished drug product in hard gelatine, two-piece capsules.
The NCE in question was a small molecule (Mr<500) and characterised by a high aqueous solubility, especially in acidic media. The proposed formulation was a lipid-based suspension in a macrogolglyceride of a vegetable oil. However due to the high dose required, the distribution of the active in the formulation was erratic and attributed to large agglomerates of particles in suspension. This resulted in inconsistent uniformity within the filled capsules which required our investigation.
Results & Discussion
Our development scientists investigated the solid state properties of the API in relation to defining the Optimal particle size distribution and understanding the rheological properties of the suspension.
This involved exploring different manufacturing parameters in order to achieve consistent and optimal content uniformity in the drug product. Our final process included a homogenisation step using a high hear mixing rotor/stator homogeniser during the production of the highly concentrated suspension of the active.
We were able to verify this through light microscopy imaging (before and after) and validate the effectiveness of our approach and solution through measurement of the homogeneity of the suspension that was consistent and we quantified the API content in the final capsules that were shown to be in conformance with the drug product release specification.
Conclusions
- Tillotts Services successfully optimised the production process for our Customer’s formulation within the agreed timeframe.
- As validated by our studies, a high shear rotor/stator homogenisation step was subsequently included in the production process.
- The resulting formulation was a thixotropic suspension with no sedimentation during manufacture or after the capsule filling.
- Phase II production was carried out in our liquid-fill GMP manufacturing facility and project managed to effect subsequently delivery finished drug product for our Customer’s clinical trials.