The impact of glidant addition on the loss-in-weight feeding of active pharmaceutical ingredients

Abstract

In recent years, continuous manufacturing (CM) has become increasingly popular in the pharmaceutical industry for the production of oral solid dosage (OSD) forms. Most of the newly developed active pharmaceutical ingredients (APIs) nowadays are extremely cohesive and sticky with a mean particle size particle of $<$ $100 μ m$ , a wide particle size distribution (PSD) and a high tendency to agglomerate, making them difficult to accurately dose using loss-in-weight equipment during CM. In this research paper, the effect of various glidants on the volumetric and gravimetric feeding of several APIs was assessed.

Three challenging APIs (acetaminophen micronized (APAP $μ$ ), metoprolol tartrate (MPT) and spray dried placebo (SD)) and four different glidants (Aerosil® 200, Aerosil® R972, Syloid® 244FP and TRI-CAFOS® 200-7) were selected. For all feeding trials, a GEA compact feeder (CF) equipped with 20 mm concave screws was used, in combination with an external catch scale. The volumetric feeding trials showed the ability of each glidant to increase the maximum feed factor ( $F F max$ ) and reduce the feed factor moving relative standard error till 40% hopper fill ( $F F movRSD40$ ) and the feed factor decay ( $F F decay$ ) for the cohesive APIs (APAP $μ$ and MPT). Although the fumed silica grades showed the highest impact on the previously mentioned feeding parameters, low aerated energy at 10 mm/s (AE10) values were obtained, negatively affecting the feeding performance at higher glidant concentration.

Both Syloid 244FP and tricalcium phosphate (TCP) were good alternatives. However, to obtain a similar feeding performance a higher concentration of these glidants is required. The volumetric trials showed that glidant addition has no additional benefits for APIs with good flow properties such as SD. The second part of this paper discussed the impact of glidant addition on the gravimetric feeding behavior of the cohesive powders. Both the fumed silica grades (Aerosil® 200 and Aerosil® R972) and Syloid 244FP lowered the deviation on all label claim % (LC (%)) profiles of the cohesive APIs. In contrast to the volumetric trails, blends with excess fumed silica resulted in low AE10 values which are efficiently dosed by the CF during the gravimetric feeding.