(W1230-11-70) Characterization of a New Multifunctional Disintegrant for Continuous Manufacturing

Purpose: Continuous manufacturing (CM) has gained interest in the pharmaceutical industry because of its economic and technical superiority to traditional batch manufacturing. One challenge of CM is the precise and reliable powder feeding requirement to meet critical quality attributes (CQAs) of pharmaceutical products. Thus loss-in-weight feeders (LWFs), which gravimetrically control powder feed rate, are typically employed, and feeder performance testing using LWFs can confirm CM feeding process robustness. In this study, the powder flow and self-lubricating properties of a new multifunctional co-processed disintegrant was evaluated by the use of an LWF, and potential performance benefits were identified. This multifunctional disintegrant was found to exhibit superior powder flow and self-lubricating properties with the benefits of reducing processing steps, simplifying manufacturing, and enhancing manufacturing efficiency and product performance in CM.

Methods: At first, the flowability of materials were evaluated using a Brookfield shear cell and a K‑Tron KSU-II LWF using auger twin screws at a nominal feed rate of 12 kg/h. Next, feed studies were conducted using multiple K‑Tron feeders feeding into Gericke Tubular continuous blender at 7, 10, and 20 kg/h, using APAP as the model drug. For the formulation with new multifunctional disintegrant three feeders were used, and for those with Crospovidone XL-10 five feeders were used (Figure 1). During each trial, the values of drive command percentage [i.e. motor velocity] (CMD %), net weight (kg), and mass flow rate (kg/h) were recorded. The blends from each feed rate were compressed into 500 mg tablets at 25kN using 11mm round tooling on an Elizabeth-Hata tablet press (38 stations) in production runs at 30 rpm for 15 minutes. Compression forces during the tableting press running cycle, ejection forces at each compression force, and tablet characterization of each blend were determined.

Results: Pure material characterization revealed that the new multifunctional disintegrant was more freely flowing than Crospovidone XL-10, silica and sodium stearyl fumarate (SSF) (Figure 2). At a feed rate of 12 kg/h, the new disintegrant demonstrated lower average CMD% and higher feed factor than Crospovidone blend (Figure 3). The particles of the co-processed excipient were well coated with glidant and lubricant, and thus were less cohesive. For the feeding study, at ribbon speeds of 7, 10 and 20kg/h, the APAP formulation with new multifunctional disintegrant demonstrated a higher feed factor, lower average CMD%, and smaller RSD% for mass flow rate than the formulation with Crospovidone XL-10 blend. During tableting, the APAP formulation with the new multifunctional disintegrant showed less variation in compression force during the tableting cycle, less weight variation, and yielded harder tablets than the Crospovidone XL-10 formulation. Lower CMD% and CMD% standard deviation indicate superior flow of the new disintegrant. This suggests that this new co-processed disintegrant not only enhances powder flow but also improves tableting performance during continuous and batch processing.

Conclusion: The new multifunctional direct compression superdisintegrant, co-processed with a glidant and lubricant possesses enhanced flow properties and provides better tableting performance with lower ejection force during continuous and batch processing. Benefits of all-in-one multifunctional disintegrant a high Feed Factor and low RSD in Loss-in-weight feeding (LWF), while enabling flexibility in choice of fillers and binders. It is designed to be economical to use by reducing production times simplifying both continuous and batch manufacturing.

References: Leuenberger H. New trends in the production of pharmaceutical granules: batch versus continuous processing. Eur. J. Pharm. Biopharm. 2001: 52(3): 289-96

Figure 1: Feeder study design for APAP tablet blends

Figure 2: superior flowability of the new multifunctional disintegrant Brookfield flow function

Figure 3: loss-in-weight feeding (LWF)