Artur Saramago, Nuno F. Costa, Slavomira Doktorovova, Claudia Moura
R&D Drug Product Development, Hovione Farmaciência S.A., Campus do Lumiar,
Building S, 1649-038 Lisboa, Portugal

Purpose. Conventionally, the development of the dry granulation process involves the execution of non-GMP batches to optimize the process conditions, leading to increased time and material demands. The present study aims to establish a material sparing methodology at the lab-scale to facilitate a direct scale-up without the necessity of conducting extensive additional non-GMP trials.

Methods. Placebo spray dried dispersions (SDDs) of HPMCAS or PVP/VA were blended with conventional excipients used in the manufacture of oral dosage forms (microcrystalline cellulose, fumed silica, croscarmellose silica, and magnesium stearate, 60% w/w SDD load). After blending, the materials were dry granulated (by roller compaction, at the manufacturing scale, or by slugging and milling, at the lab-scale), extragranular blended and compressed into tablets on a compaction simulator. Different granulation process conditions were applied to enhance the robustness of the methodology.

Results. The application of higher forces and narrower gap settings during granulation resulted in granules with higher particle sizes, as result of the higher solid fractions of the ribbons. Overall, the work has shown that independently of the process conditions during granulation at the manufacturing scale, the production of slugs at the lab-scale (targeting the same out of gap solid fraction) yielded granules with equivalent particle size distributions and compressibility, tabletability, and compactability profiles.

Conclusions. This work demonstrated it is possible to predict the dry granulation process using a lean methodology at the lab-scale. This methodology significantly minimizes the API needs and accelerates the process development stage by enabling right-first-time scale-up from lab to manufacturing.