Search for a command to run...
Carbamazepine, an antiepileptic drug, crystallizes in its usually observed needlelike dihydrate form (CBZ-DH) via antisolvent crystallization. In this work, we have investigated the influence of additives on the shapes and sizes of CBZ-DH crystals produced from ethanolic solution using water as an antisolvent. The influence of four relevant polymeric additives─polyethylene glycol (PEG), sodium dodecyl sulfate (SDS), hydroxypropyl methylcellulose (HPMC), and Poloxamer 407─at different loadings was initially investigated on the vial scale. HPMC was found to have the most significant impact on CBZ-DH crystals, leading to block-like particles in the vials, while the needlelike morphology persisted in the presence of the other additives. HPMC was selected for further investigations using continuous antisolvent crystallizers. The experiments were performed using HPMC as an additive with two types of crystallizers: a stirred tank crystallizer (CSTC) and a crystallizer comprising a fluidic oscillator (FO) and helical coil (HC). While the X-ray powder diffraction (XRPD) of the lab-scale crystalline product does not differ from the XRPD at the vial scale, implying the dominance of the same crystal face during growth, kite-shaped crystals of CBZ-DH were formed in the continuous crystallizer. Comparison of the length and width distributions of these crystals and the steady-state yield of CBZ-DH with the crystals produced in the absence of additives suggested retarded kinetics under the impact of additives. The coefficient of the growth rate estimated using population balance models was lower in the presence of HPMC. The kite-shaped crystals of CBZ-DH reported in this work will provide an impetus for experimental and modeling-based studies of the impact of additives on the shape of crystals, which can be taken advantage of for enhanced dissolution profiles.