Kara Aytug, Kumar Dinesh, Healy Anne Marie, Lalatsa Aikaterini, Serrano Dolores R
Departament of Pharmaceutics and Food Science, School of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain.
Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi 221001, India.
Pharmaceuticals (Basel). 2023 Jul 27;16(8):1064. doi: 10.3390/ph16081064.
Using cocrystals has emerged as a promising strategy to improve the physicochemical properties of active pharmaceutical ingredients (APIs) by forming a new crystalline phase from two or more components. Particle size and morphology control are key quality attributes for cocrystal medicinal products. The needle-shaped morphology is often considered high-risk and complex in the manufacture of solid dosage forms. Cocrystal particle engineering requires advanced methodologies to ensure high-purity cocrystals with improved solubility and bioavailability and with optimal crystal habit for industrial manufacturing. In this study, 3D-printed microfluidic chips were used to control the cocrystal habit and polymorphism of the sulfadimidine (SDM): 4-aminosalicylic acid (4ASA) cocrystal. The addition of PVP in the aqueous phase during mixing resulted in a high-purity cocrystal (with no traces of the individual components), while it also inhibited the growth of needle-shaped crystals. When mixtures were prepared at the macroscale, PVP was not able to control the crystal habit and impurities of individual mixture components remained, indicating that the microfluidic device allowed for a more homogenous and rapid mixing process controlled by the flow rate and the high surface-to-volume ratios of the microchannels. Continuous manufacturing of SDM:4ASA cocrystals coated on beads was successfully implemented when the microfluidic chip was connected in line to a fluidized bed, allowing cocrystal formulation generation by mixing, coating, and drying in a single step.
使用共晶体已成为一种有前景的策略，可通过由两种或更多种组分形成新的晶相来改善活性药物成分（API）的物理化学性质。粒度和形态控制是共晶体药物产品的关键质量属性。在固体剂型的制造中，针状形态通常被认为具有高风险且复杂。共晶体颗粒工程需要先进的方法来确保具有改善的溶解度和生物利用度以及适合工业制造的最佳晶体习性的高纯度共晶体。在本研究中，使用3D打印微流控芯片来控制磺胺二甲嘧啶（SDM）：4-氨基水杨酸（4ASA）共晶体的共晶体习性和多晶型。在混合过程中在水相中添加聚乙烯吡咯烷酮（PVP）可得到高纯度共晶体（无各组分的痕迹），同时还抑制了针状晶体的生长。当在宏观尺度上制备混合物时，PVP无法控制晶体习性，且各混合物组分的杂质仍然存在，这表明微流控装置允许通过流速和微通道的高表面积与体积比来实现更均匀和快速的混合过程。当微流控芯片与流化床在线连接时，成功实现了涂覆在珠子上的SDM：4ASA共晶体的连续制造，从而能够通过一步混合、包衣和干燥来生成共晶体制剂。
