Solid crystalline suspensions (SCSs) containing submicron particles were introduced as a competitive solution to increase dissolution rates and the bioavailability of poorly water-soluble drugs. In an SCS, poorly water-soluble drug crystals are finely dispersed in a hydrophilic matrix. Lately, melt milling as an adapted wet milling process at elevated temperatures has been introduced as a suitable batch manufacturing process for such a formulation. In this work, the transfer from batch operation to a two-step continuous process is demonstrated to highlight the potential of this technology as an alternative to other dissolution-enhancing methods. In the first step, a powder mixture of a model drug (griseofulvin) and a carrier (xylitol) is fed to an extruder, where a uniform suspension is obtained. In the second step, the suspension is transferred to a custom-built annular gap mill, where comminution down to the submicron region takes place. The prototype’s design was based on batch grinding results and a narrow residence time distribution, intended to deliver large quantities of submicron particles in the SCS. The throughput of the mill was found to be limited by grinding media compression. By inclining the mill at an angle, the grinding media position was manipulated, such that compression was avoided. Different states of the grinding media in the grinding chamber were identified under surrogate conditions. This strategy allows the maintenance of an energy-optimized comminution without adaption of the associated process parameters, even at high throughputs. Using this new process, the production of an SCS with 80–90 % submicron particles in a single passthrough was demonstrated.
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