In the pharmaceutical manufacturing landscape, the choice between batch and continuous manufacturing processes is a crucial challenge for operational efficiency and final product quality. A study published in the International Journal of Pharmaceutics compared the two models applied to tablet manufacturing revealing howmaterial flow dynamics play a crucial role in determining consistency and performance of the final product.
In thebatch process, the high variability in flow is reflected in the final quality of the tablets, which becomes equally variable, although with careful pre-mixing the API concentration is more stable. Overall, the researchers explain, optimizing the choice of excipients and process settings remains the most effective way to optimize the results of both methods.
The study compared trials adopting a wide range of configurations: twenty formulations including ten low-dose (1% w/w) and ten high-dose (40% w/w), combined with a variety of different excipients.
Mass of Tablets
Analysis of the ability of the materials to flow and compress effectively in the two processes highlighted the crucial role of flow dynamics. The researchers evaluated several aspects of the behavior of powder materials (such asflowability, filling uniformity, permeability and compressibility) by verifying their impact on key parameters of tablet quality, such as mass variability (σMass) and tensile strength (σTS).
In batch processes, variability in tablet mass was generally higher than in continuous processes, especially at high concentrations of active ingredient.
The highest values of variability were recorded for formulations containing more cohesive fillers, such as microcrystalline cellulose (MCC), while the more flowable and less compressible ones (e.g., co-processed lactose-lactitol 40LL and anhydrous lactose 22AN) showed the lowest levels. In detail, the variability observed was:
- 1% active ingredient: Minimum 0.60%, Maximum 1.50%
- 40% active ingredient: Minimum 1.80%, Maximum 5.70%
For the continuous process, the observed variability was:
- 1% active ingredient: Minimum 0.50%, Maximum 1.20%
- 40% active ingredient: Minimum 1.30%, Maximum 4.30%
Tensile Strength
Tensile strength was also found to be less consistent in batch processes, due to less consistency in mold filling than in continuous processes.
Intermittent powder flow tends to generate inhomogeneity in mold filling, especially with less fluid or highly cohesive materials such as microcrystalline cellulose. Overall, batch tests revealed that low and high dosage formulations were processable when aiming for a low (5 kN) or intermediate (10 kN) main compression force, whilewith higher forces (15 kN) it was found to be more difficult to maintain a constant force when the are in high concentrations (40 percent).
To reduce this variability, the study suggests taking measures such as adding glidants to improve powder flow or optimizing power system settings.
Bridging and rathole
One of the main issues that disturb the homogeneity of material flow is the formation, during passage through the feeding system, of bonds between powder material particles (so-called bridging), which resist gravitational force or pressure and interrupt the continuous flow of powder to the molds, leading to uneven fills and consequent variations in tablet quality. This phenomenon is the cause that prevented a stable batch process during the study when a main compression force of 15kN was required.
Associated with this phenomenon is that of rathole (literally “rat hole”) formation, that is, the formation of a central channel within the material through which the powder flows, leaving the material on the sides of the hopper stationary and unused.
In continuous processes, on the other hand, the powder is continuously replenished and agitated, improving the smoothness and consistency of the flow to the press. This ensures more homogeneous mold filling, contributing to better uniformity of weight and mechanical properties of the tablets.
Optimization of process parameters
Through multivariate statistical analyses, the researchers identified some correlations between material properties, process settings and final tablet characteristics.
In particular, in batch processing it was necessary to increase the values for fill depth and compressive force to compensate for variations caused by the inconsistency of powder flow.
