Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation

Abstract

Homogeneous ultralow-dose (30 mg) tablets were prepared from perfectly free-flowing granules manufactured by continuous Twin-Screw Wet Granulation. The gravimetrically fed mixture of lactose and potato starch of low particle size was successfully agglomerated and the size enlargement technology proved to be very robust. Since the incorporated drug was dissolved in ethanol-based granulation liquid, the resulting homogeneity largely depended on the dosing of the applied liquid administering units.
A peristaltic pump generated higher deviation of the drug content in tablets (Relative Standard Deviation (RSD): 7.7 %) compared to a syringe pump (RSD: 2.3 %) or a piston pump (RSD: 4.6 %). This is due to the pulsation of the liquid flow generated by the peristaltic pump according to the real-time measured mass of the fed liquid. A good correlation was found between the RSD of the liquid mass flow (calculated from the recorded masses) and the RSD of the drug content. Based on the results, the goodness of Content Uniformity, as the most relevant critical quality attribute of low-dose products, was determined by the characteristics of the applied dosing units. The feeding characteristic of the different pumps could be easily measured by the introduced balance-based method and therefore, the applicability of the pumps could be evaluated.