Study on Applicability of ODTs with Co-processed Excipient to Continuous Manufacturing Process
“Continuous Manufacturing (CM)” is a manufacturing method in which raw or blended materials are continuously charged to the processing line, and products are continuously discharged throughout the duration of the process. CM method is of great significance from the perspective of manufacturing operations, medical professionals and patients. In this study, we verified applicability of orally disintegrating tablets (ODTs) to CM. We produced ODTs with our co-processed excipient, which is “HiSORAD”, by applying dry granulation process. Co-processed excipients seem to be suitable to CM as they can reduce numbers of control parameters required to maintain appropriate quality.
We selected the following ingredients for our experiments; HiSORAD HSR-D03 (HSR) was used as filler, ethenzamide (ETZ) was chosen as model API and Sodium Stearyl Fumarate (SSF) was used as lubricant. These ingredients were able to be granulated by the dry granulator. Granules with HSR have large particle size.
In case of CM, “Quality by Design (QbD) approach is important from the perspective of a control strategy for pharmaceutical quality. QbD involves designing the product quality maintained by accurate process control, such as real-time monitoring of physical properties of continuously produced granules. We show the results of real-time monitoring for the particle size distribution by PAT tool. In case of D90, there was large variation of the particle size at the beginning. it came down immediately and fell within a certain range. On the other hand, D50 stayed within a certain range until the end. These preliminary studies have suggested that our co-processed excipient can be applied to CM method.
The obtained granules were tableted by the rotary tableting machine. All ODTs showed sufficient disintegratability and tablet hardness. HSR showed good compactability even at high API dosage and low compression force. Moreover, it was found that ETZ particle was uniformly dispersed in both granules and the tablet. HSR is expected to have high applicability for DG system in CM since it is unlikely to cause separation and segregation of API.
In conclusion, co-processed excipient “HiSORAD” can be applied to the DG system in continuous manufacturing, while maintaining high productivity and high quality of ODTs. Co-processed excipient may be more useful compared to single excipients in terms of quality control in continuous manufacturing.
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