Solid State Pharmaceutical Research Group (SSPRG), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
Drug Deliv Transl Res. 2018 Dec;8(6):1726-1739. doi: 10.1007/s13346-018-0479-7.
The last decade has witnessed extensive growth in the field of co-crystallization for mitigating the solubility and dissolution-related issues of poorly soluble drugs. This is largely because co-crystals can modify the physicochemical properties of drugs without any covalent modification in the drug molecules. The US Food and Drug Administration (FDA) now considers drug products that are designed to contain a new co-crystal, analogous to new polymorph of the active pharmaceutical ingredient (API). This positive change in regulatory perspective coupled with successful commercialization of valsartan-sacubitril co-crystal (Entresto, Novartis) has now brought co-crystals into focus, in both industries as well as academia. Co-crystal prediction, screening, and synthesis have been reported in literature; however, co-crystal production at a larger scale needs further investigations. With this aim, the article describes various continuous methods for co-crystal production, along with in-line monitoring during co-crystal production, emphasizing on process analytical technology (PAT). In addition, the scale-up issues of continuous and batch co-crystallization and other suitable techniques for pharmaceutical scale up are detailed. Quality control aspects and regulatory viewpoint crucial for commercial success are elaborated in the future perspective.
过去十年，共晶技术在解决难溶性药物的溶解度和溶解相关问题方面取得了广泛的发展。这在很大程度上是因为共晶可以在不改变药物分子的任何共价修饰的情况下改变药物的物理化学性质。美国食品和药物管理局（FDA）现在认为，旨在包含新共晶的药物产品类似于活性药物成分（API）的新多晶型物。这种监管视角的积极变化，加上缬沙坦-沙库比曲共晶（Entresto，诺华）的成功商业化，现在使共晶成为焦点，无论是在工业界还是学术界。文献中已经报道了共晶的预测、筛选和合成；然而，更大规模的共晶生产需要进一步的研究。为此，本文描述了各种连续生产共晶的方法，以及在共晶生产过程中的在线监测，重点介绍了过程分析技术（PAT）。此外，详细讨论了连续和分批共结晶的放大问题以及其他适合制药放大的技术。未来展望部分阐述了质量控制方面和对商业成功至关重要的监管观点。
