Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing

Abstract

Minimizing variability in the feeding process is important for continuous manufacturing since materials are fed individually and can impact the final product. This study demonstrates the importance of measuring powder properties and highlights the need to characterize the feeding performance both offline with multiple refills and in the intended configuration for the continuous manufacturing equipment. The standard grade hydroxypropyl methylcellulose (HPMC) had material buildup on the loss-in-weight feeder barrel from triboelectric charging and resulted in more mass flow excursions and failed refills which were not observed with the direct compression grades. The location of the electrostatic buildup changed when the feeder was connected to a hopper instead of feeding offline into a collection bucket. Overall, the direct compression HPMC exhibited better flow which resulted in more accurate loss-in-weight feeding with less excursions from the target mass flow and all refills were completed in the first attempt. The improvements with the direct compression HPMC would be beneficial when running any continuous process (wet granulation, roller compaction, or direct compression) or other processes where loss-in-weight feeding is utilized, such as melt extrusion or twin screw granulation.

Assessment of Tribo-charging and Continuous Feeding Performance of Direct Compression Grades of Isomalt and Mannitol Powders

“…2j and k). Similar findings have been observed, to a higher extent, by Allenspach et al when feeding hydroxypropyl methylcellulose (HPMC) K4M powder and have been associated to an electrostatic powder build-up [23].…”

“…Therefore, there is a growing interest in characterizing the tribo-charging tendency of powders as a critical material attribute for feeding performance [19][20][21]. Powders adhering to the feeder surfaces undergo higher tribo-charging, resulting in stagnation in the hopper, reduction of the screw free volume, bearding effects at the screw outlet (i.e., adhesion to the screw outlet), and alteration to the powder trajectory during freefall motion [22] and hopper refilling [23]. This can block feeder refilling leading to poor accuracy and consistency of the dosed mass, which may propagate throughout the process and lead to products with varying content of active pharmaceutical ingredient(s) (APIs).…”

Impact of Powder Properties on the Rheological Behavior of Excipients

“…This indicates that cohesiveness increases with rotational speed, which is associated with more intermittent and irregular flow. This can be concern for the pharmaceutical industry as more cohesive powders can lead to increased variability and mass flow excursions outside the acceptable target range, as demonstrated by Allenspach et al [ 37 ]. Notable is the shear thinning behavior, which is observed for two grades of anhydrous lactose, two grades of lactose monohydrate and microcrystalline cellulose.…”

Review: Continuous Manufacturing of Small Molecule Solid Oral Dosage Forms

“…The importance of choosing the correct grade of excipient in a CM operation is highlighted in a recent paper by Allenspach et al [ 107 ]. They found that different grades of HPMC showed different tribocharging properties when fed into a CM process from a loss in weight feeder.…”