(200af) Dropwise Manufacturing of Oral Solid Dosage Forms Using Powder Slurries | AIChE

(200af) Dropwise Manufacturing of Oral Solid Dosage Forms Using Powder Slurries


Radcliffe, A. J. - Presenter, Purdue University
Nagy, Z. K., Purdue University
Reklaitis, G. V., Purdue University
As part of the shift toward continuous processing in the pharmaceutical industry, there has been considerable interest for adaptation/development of advanced manufacturing methods due to potential advantages in product quality, flexibility of scale-up and drug delivery. Inkjet printing technology, or adaptation thereof, has been the focus of much academic/industrial research efforts for use in oral solid dose manufacturing due in part to the extent of control over product properties enabled by precision deposition of small volumes of active ingredient or excipient [1]. Such applications of inkjet printing to pharmaceuticals have examined the use of several methods for liquid dispensing that may be distinguished based on factors such as actuation method (e.g. thermal, piezoelectric), the mode of fluid deposition – as individual drops, liquid jet, or continuous filament – and by physical dimensions of the ejected liquid volumes, which range in diameter from a few micrometers (e.g. inkjet printing, 3D printing) to a few millimeters (e.g. this system) [1]. The development of multiple liquid dispensing methods has been motivated by the variety of applications related to production of low dose drugs, creation of novel drug formulations and integration with continuous or semi-continuous manufacturing strategies. Fluid formulations for these processes may be adjusted to the performance requirements of the equipment, or may be tuned to achieve specific properties in a drug product; flexibility in this aspect is documented in the literature, as formulations based on drug solutions, eutectic melts and suspensions of drug nanoparticles have been used to produce solid oral doses. [1, 2, 3]

In this work, a dropwise manufacturing platform is used to produce high dose drug products using concentrated suspensions of non-Brownian particles. Pharmaceutical powders are selected based on achievable particle sizes (1-500µm) from controlled crystallization unit operations, and suspensions are formed with volatile/non-volatile carrier liquids for delivery onto suitable substrates by dropwise addition. The resultant solid oral dosages are analyzed for their mass/composition content uniformity and for the extent of preservation of particle size distribution before/after printing. Process performance metrics for dropwise manufacture of solid oral dosage forms using particle suspensions are presented in terms of drop volume/mass statistics and process throughput (number of doses per unit time); the effects of suspension properties (e.g. particle loading, particle size) on drop volume/mass and process throughput are clarified using the rheological behavior observed through high speed photography of the drop formation process [4].


  1. Daly, R., Harrington, T. S., Martin, G. D., & Hutchings, I. M., 2015. Inkjet printing for pharmaceutics – A review of research and manufacturing, International Journal of Pharmaceutics, 494, 554-567.
  2. Içten, E., Purohit, H. S., Wallace, C., Giridhar, A., Taylor, L. S., Nagy, Z. K., & Reklaitis, G. V., 2017. Dropwise additive manufacturing of pharmaceutical products for amorphous and self emulsifying drug delivery systems. International journal of pharmaceutics, 524(1), 424-432.
  3. Bonhoeffer, B., Kwade, A., & Juhnke, M., 2017. Impact of formulation properties and process parameters on the dispensing and depositioning of drug nanosuspensions using micro-valve technology. Journal of pharmaceutical sciences, 106(4), 1102-1110.
  4. Radcliffe, A. J., & Reklaitis, G. V., 2017. Dropwise Additive Manufacturing using Particulate Suspensions: Feasible Operating Space and Throughput Rates. In Computer Aided Chemical Engineering(Vol. 40, pp. 1207-1212). Elsevier.