(586t) Continuous Direct Compaction As a Manufacturing Route for Highly Segregating Blends

Pharmaceutical solid oral dosage formulations in which the difference in particle size of the active ingredient and excipients is large have been processed via continuous direct compaction to produce tablets that comply with quality regulations.

Granular mixtures with distinctly bimodal size distributions tend to de-mix. Granular segregation based on particle size is a bane in the pharmaceutical industry since a difference in the particle size of the active ingredient and the excipients can cause in-process demixing leading to poor content uniformity at the tablet level. Such formulations are thus granulated to ensure homogeneity at the powder level which translates into tablets with robust content uniformity.

Recent advancement in continuous pharmaceutical processing was leveraged and highly segregating granular mixtures were processed in a continuous direct compaction line to produce acceptable tablets. The phenomenon has been exhibited by performing trials with a variety of such formulations. The most extreme case is a formulation where the particle size of active ingredient is 12 times that of the major excipient. The authors believe that the fundamental premise of a continuous process, that, at steady the rate of input equals the rate of output coupled with the fact in a continuous process, a much lower volume of material is present in the system as opposed to a batch process where the whole batch is ‘in process’ are key reasons behind being able to handle such systems via direct compaction.

Direct compaction is a cheaper processing route than wet or dry granulation and involves fewer unit operations. Continuous direct compaction eliminates uncertainty associated with its traditional batch cousin and thus presents the possibility of making several products via this route which are currently being made via the granulation routines. This could prove to be an industry game changer.