Conventional manufacturing of tablets (solid dosage forms) demand multiple unit operations and handling of powders and solids for every step of the formulation process, which is known to be more challenging compared to handling liquids. To circumvent these challenges, this study explored liquid dispensing to manufacture oral solid dosage forms for the active pharmaceutical ingredient (API) Modafinil (MOD). The additive manufacturing process dispenses a solution (API, solvent, polymer) into substrates. Upon solvent evaporation under controlled conditions the MOD crystallizes inside a polymer matrix generating a crystalline solid dispersion (CSD). The critical process parameters (e.g., temperature, concentration, evaporation rate, choice of solvent) for the CSD manufacturing process were evaluated to determine the thermodynamic design space that ensures the desired MOD polymorph is crystallized. The CSDs were characterized by PXRD, Raman spectroscopy, DSC, and TGA for polymorphic control and solid form purity. Drug loading, content uniformity, and dissolution studies followed US Pharmacopeia methods and were compared to commercial tablets of MOD.This study demonstrates that MOD form I crystallization, needed in the solid dosage formulations, can be achieved, and embedded in a polymer matrix by a controlled evaporative crystallization process from a polyethylene glycol – methanol solution. The performance characteristics of the additively manufactured CSDs are compared to the commercial tablets of MOD sold under the trade name Provigil®.The coupled crystallization and formulation process in this study enables flexible small-scale manufacturing of solid dosage forms via process intensification.1
(1) Stelzer, T.; Lakerveld, R.; Myerson, A. S. Process Intensification in Continuous Crystallization. In The Handbook of Continuous Crystallization; Yazdanpanah, N., Nagy, Z. K., Eds.; The Royal Society of Chemistry, 2020; pp 266–320. https://doi.org/10.1039/9781788013581-00266.
