(308d) A Robust Micro-Dosing Approach for Pharmaceutical Powders Based on a Small-Scale Powder Pump Concept

Despite recent developments in the field of micro-dosing of pharmaceutical powders, the exact dosing of cohesive powders remains challenging. Either the dosing equipment needs to be adjusted to the flow characteristics of the powder or the range of powder is limited to specially engineered powders exhibiting favorable behavior. Choosing the right option requires extensive investigation on the powder characteristics and adjustments of the feeding device based on experience. A promising technique showing low sensitivity to the powder characteristics is a micro-feeder based on a powder pump concept ^1–3 . While this technique is originally applied for providing low feed rates of pharmaceutical powders to continuous processes^1–3, its robustness is also promising in the field of micro-dosing. A fast and robust solution for dosing small amounts of powder precisely, i.e., 10 to 500 mg, could speed up formulation development and early-stage manufacturing, and enable the production of personalized medication.

Investigating if this powder pump concept is capable to fulfill these requirements, a device was developed combining the feeding device itself, and a weighing cell to allow gravimetric dosing. A control strategy was developed increasing dosing precision by continuous monitoring of the dispensed volume and the dosed mass. Based on these quantities the bulk density in the relevant volume of the powder bed is calculated iteratively allowing a precise estimation of the volume that needs to be dispensed. The performance of the built device was assessed in experiments with different pharmaceutical powders, i.e. lactose monohydrate (Flowlac 90, Capsulac 60, Sorbolac 400), microcrystalline cellulose (Emcocel 90M, Vivapur 12, 101, 105, 200), magnesium stearate, and Ibuprofen 25. Furthermore, the influence of process parameters such as the speed of the pump piston, the scraper speed, and the number of partial doses on the dosing precision was studied.

The talk will highlight the influence of cohesion on the dosing precision and overcoming limitations regarding this influence by mechanical adjustments to the device, tuning of the process parameters, and the implemented control strategy. Based on the experimental data the benefits and limitations of this dosing concept, compared to state of the art equipment, will be discussed.

Literature Cited

1. Besenhard MO, Fathollahi S, Siegmann E, Slama E, Faulhammer E, Khinast JG. Micro-feeding and dosing of powders via a small-scale powder pump. International journal of pharmaceutics. 2017;519(1-2):314–322.
2. Fathollahi S, Sacher S, Escotet-Espinoza MS, DiNunzio J, Khinast JG. Performance Evaluation of a High-Precision Low-Dose Powder Feeder. AAPS PharmSciTech. 2020;21(8):301.
3. Sacher S, Heindl N, Afonso Urich JA, Kruisz J, Khinast JG. A solution for low-dose feeding in continuous pharmaceutical processes. International journal of pharmaceutics. 2020;591:119969.