The unit operations that comprise our Integrated Continuous Manufacturing lines are novel, and provide advantages over existing conventional batch technologies. They permit reactions and formulation steps that are not possible in batch. The following unit operations are examples of process technologies we can implement for our clients:
Continuous Reactor to Handle Solids in flow
A reactor with a particular geometry which favors handling solids in continuous flow
- Description: Developed for fast, exothermic reactions, the geometry of this reactor enables solid particulates to be processed in flow.
Membrane Separator By-Pass
A system that allows automated cleaning in place of liquid-liquid membrane separators
- Description: Separates aqueous and organic streams without headspace, including difficult emulsions. The system automatically detects when membrane fouling occurs, responding by bypassing the compromised membrane to a fresh separation unit in addition to cleaning the fouled membrane. Upon completion of cleaning, the system reverts back to the first membrane separation unit.
Process to crystallize an API directly on the excipient surface
- Description: API in different solutions can be crystallized on crystalline or polymeric excipients to eliminate downstream processes such as granulation.
Integrated Nucleator and Tubular Crystallizer
Device to produce particles with mono-disperse, very narrow size distribution
- Description: A supersaturated solution is run into a nucleator device containing a specific seed initiating the nucleation process. Particles are then transferred into a tubular (plug flow) crystallizer where growth occurs.
Continuous, small scale rotary filtration and washing system for the purification of concentrated suspensions containing active pharmaceutical ingredients (APIs) or API intermediates
- Description: A Continuous Rotary Filter purifies the crystallization slurry, removing unwanted impurities from the Active Pharmaceutical Ingredient (API) or intermediate product. The slurry is deposited on a rotating porous plate, where the mother liquor is filtered out through a high vacuum system. The thin (~1 mm) wet-cake is effectively and efficiently purged of impurities through the application of multiple wash stations, after which it is transported to the next unit. A built-in Clean-In-Place mechanism restores the filter plate, while the purified wet-cake is analyzed with in-line PATs for real-time purity and concentration. The system has the ability to segregate filtrate streams, enhancing solvent recovery.
Rapid, continuous, small-scale device that forms dry powder from a concentrated or diluted suspension that contains active pharmaceutical ingredients (APIs)
- Description: A Continuous Drum Dryer converts concentrated or diluted suspensions containing the API into a dry, flowable powder. The suspension is deposited onto two heated rotating drums, forming thin layers that are quickly dried. Concurrently, a specified load is applied between the two drums, reducing particle size to the desired specification. The entire system is under vacuum, allowing the process material to be maintained at lower temperatures. The dried API is then conveyed through a cyclonic separator, before it is sent to the next unit operation. In-line PATs allow for real-time measurement of particle size, residual solvent and crystal form.
Extrusion Molding Coating (EMC)
Integration of extrusion and moulding processes for the continuous manufacturing of pharmaceutical tablets
- Description: An Integrated Extrusion-Molding-Coating process produces pharmaceutical-grade coated tablets in a continuous fashion. The API and required excipients are fed into the unit, where they are heated and mixed, resulting in a uniform melt, or extrudate. Coated tablets are then produced as this process material is molded and coated in subsequent sections of the unit. In-line PATs allow for real-time measurement of content uniformity and crystal form. The entire system operates solvent-free.
Continuous process (powder handling free) for transforming a solution or suspension into pharmaceutical tablets
- Description: A process for manufacturing solid oral dosage forms directly from solutions of purified API. A solution is processed either through thin-film casting or electroprocessing to produce a thin layer of an API/excipient matrix. The film is subsequently engineered to form tablets of consistent physical dimensions (e.g. thickness, diameter and mass). All steps are continuous and run in an integrated manner.