(566g) A New Approach Towards the Production of a Personalizable Dry Solid Dosage Form for Biologics: In-Vial Direct Dosing and Drying By Inkjet Printing

The interest in therapeutical relevant proteins and peptides is increasing steadily, not only because of the growing number of promising candidates but also because of their unique therapeutic potential (Senior, 2022). These biologics are highly diverse in terms of molecular size, resulting in different physical properties and different sensitivity to chemical and physical influences occurring during processing or storage. According to their variety in target and site of action, they require a wide range of dosage forms and thus manufacturing technologies. Additionally, due to the proteins’ plethora, production quantities range from several kg/year up to 100 kg/year (Pennington et al., 2021). Respectively, the production of a final (personalized) dosage form for biologics is of interest on both large and small scales. Considering the storage stability under normal conditions, the transfer of proteins from their liquid state into dry, solid powders is advantageous.

To this end, we developed a new personalizable concept of directly dosing the protein solution (i.e., ink) via inkjet printing into the final vial, followed by a gentle drying step to end up in a stable dosage form. In our study, Human Serum Albumin (HSA, approx. 66kDa) stabilized in phosphate buffered saline was used as a model protein. Dispensing a single (personalizable) dose of protein into its final vial was achieved via an industrial inkjet printer. Subsequently, vacuum drying at ambient temperature and 50 mbar was applied.

All investigated DoE formulations were printable fluids, but within the satellite droplets regime (Oh<0.10, 40<Re<125) (Derby, 2010). Thereby, we found PS80 to be crucial for reducing the jetted drop angle to allow for precise drop deposition at the vial bottom. Further, the residual moisture of the dried doses revealed acceptable water content (<10wt%) to maintain the protein flexibility and long-term stability. Therefore, the two optimized formulations were consistently printable and no increase in protein aggregation was detected when printing over prolonged time period. Further, 93% of a targeted dose were successfully dispensed into the final vial and reconstitution volumes down to 100µl resulted in no significant loss in reconstituted dose. To conclude, the developed concept is a promising approach to broaden the available processes for (personalizable) flexible production of solid dosage forms, allowing for fast adaption of production scales.

Literature:

Derby, B., 2010. Inkjet printing of functional and structural materials: Fluid property requirements, feature stability, and resolution. Annu. Rev. Mater. Res. 40, 395–414. https://doi.org/10.1146/annurev-matsci-070909-104502

Pennington, M.W., Zell, B., Bai, C.J., 2021. Commercial manufacturing of current good manufacturing practice peptides spanning the gamut from neoantigen to commercial large-scale products. Med. Drug Discov. 9, 100071. https://doi.org/10.1016/j.medidd.2020.100071

Senior, M., 2022. Fresh from the biotech pipeline: too much, too fast? Nat. Biotechnol. 40, 155–162. https://doi.org/10.1038/s41587-022-01208-2