Since conception, continuous pharmaceutical manufacturing has remained in the shadow of batch manufacturing. Traditional feasibility studies, validation runs, and regulation oversight have contributed to a delay in widespread adoption. One such area of old-fashioned and usually fixed thinking is blending. In batch manufacturing, ingredients are added individually, in large masses, into bins, requiring significant blending to achieve a homogeneous state. On the other hand, in continuous manufacturing, individual components are usually added at less than 50 grams per second to a continuous process stream that regularly has less than 3 kg of material in transition throughout the manufacturing line at a given time. While blending in batch processes has been well established due to its simplification, the dynamics of continuous manufacturing introduce complexities that challenge traditional thinking. Residence time distribution is one of the critical concepts in continuous manufacturing. Evaluation of residence time distribution using spectroscopic unique tracers has shown that the tracer distribution curves appear as sharp, distinct, peak in concentration with a slight tail exiting the continuous blender. The tracer continues down the CM line, primarily in a plug flow state, until it reaches the feed frame of the tablet press. When the concentration curve of the tracer is evaluated in the feed frame , the peak of the curve has decreased by over two thirds, has a wide distribution, and is commonly a long tail. This concentration curve is similarly observed in the tablets collected after compaction. The evidence identifies that more mixing occurs in the feed frame of the tablet press than in the continuous blender, leading to the question.
Is a blender necessary for a continuous manufacturing line?
This study the mixing capabilities of a continuous manufacturing line of loss-in-weight (LIW) feeders dispensing into a continuous blender and tablet press, an IBC bin blender dispensed directly into a tablet press, and LIW feeders dispensing individual components to a tablet press with a single pitch blade mixer placed in the hopper of the tablet press were compared to the mixing capabilities of LIW feeders dispensing directly into a tablet press, with only the feed frame of the press to provide the mixing. The formulation utilized for this study was a well flowing, high-dose formulation consisting of 50 %w/w Compap L™, 44 %w/w Prosolv® HD90, 5 %w/w pregelatinized starch, and 1 %w/w MgSt. Blend homogeneity (BH) was monitored within the feed frame of a tablet press and the critical quality attributes of the tablets, such as weight variability, hardness variability, tensile strength, and API content, were evaluated. The results showed that the blend homogeneity for each manufacturing process reached a similar level of homogeneity. The findings indicate that using LIW feeders to dispense directly into the tablet press can generate a homogeneous blend that can match BH for batch and continuous blending. The results of this study provide a potential alternative to significantly reduce manufacturing costs and allow for more rapid product development.
