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The overall objective of this study was to provide 'semi-quantitative' or 'rigorous' definitions of the fluidity, lubricity and compactibility requirements of formulation for representative dosator and dosing disc capsule filling machines. To that end, model formulations were developed for those properties using Carr's compressibility index, ejection force, and plug breaking force at a specified compression force to gauge fluidity, lubricity, and compactibility, respectively. These formulations were each encapsulated on an Hofliger-Karg GKF-400 dosing disc machine and a Zanasi LZ-64 dosator machine. Each machine was instrumented to measure plug compression and ejection forces. The encapsulation process was evaluated for %CV of fill-weight, ejection force, plug breaking force and the dissolution of marker drugs incorporated in the formulations. The f 2 metric was used to compare dissolution profiles. The results suggest: (1) formulations should meet different flow criteria for successful encapsulation on the two machines, (2) a relatively lower level of lubricant may be sufficient for the dosing disc machine, (3) a higher degree of formulation compactibility is needed for the dosator machine, and (4) transferring formulations between these machine types (same class, different subclass per FDA's SUPAC-IR/MR Manufacturing Equipment Addendum) could be challenging. In certain cases dissolution profiles for the same formulation filled on the two machines with equivalent compression force were different based on f 2 < 50. Overall, the results of this study suggest a range of formulation characteristics appropriate for transferring formulations between these two types of machines.

The objective of this study was to simulate powder plug formation and explore the low-force powder compression physics of the process. A single-ended saw-tooth waveform was used to make powder plugs, representing no. 1 size capsules, at constant punch speeds of 1, 10, and 100 mm/sec on a tablet compaction simulator. Plugs of different heights (4, 8, and 12 mm) were made in a prelubricated die from three materials: Avicel PH 102, anhydrous lactose, and Starch 1500. The compression data were fit to Heckel's pressure-density relationship, Kawakita's pressure-volume relationship, and Shaxby-Evans's exponential relationship. Heckel analysis of this low-pressure range data revealed "apparent yield pressures" of 25-70 MPa, which were dependent upon the material type, machine speed, and plug height. Shaxby-Evans's relationship was found to hold in that the axial load transmission decreased exponentially with increased plug height/diameter ratio. A dramatic decrease in the coefficient of lubrication, R, with increase in plug height was attributed to poor axial load transmission through the length of the plug. Kawakita's pressure-volume relationship fit the plug formation data very well, and it was evident from this model (Kawakita constant, a) that Avicel PH 102 had the largest available volume for reduction. The plug formation process can be simulated using a programmable tablet compaction simulator. Overall, the data analysis demonstrated that the compression models available for tableting that were used in this study can also be applied to the powder plug formation process with appropriate interpretation.

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