Rao Roshan P, Natarajan Jawahar, Khanra Samanwita, Pachiyappan Jey Kumar, Nizam Imrankhan, Muralidhara Akshay, Selvaraj Jubie, Selvamuthukumar S
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, 643001, India.
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, 643001, India.
AAPS PharmSciTech. 2025 Oct 4;26(8):233. doi: 10.1208/s12249-025-03228-y.
Poor oral bioavailability in most modern pharmaceuticals is primarily caused by poor aqueous solubility. Most NCEs (New Chemical Entities) and nearly 40% of drugs on the market fall into either Biopharmaceutical Classification System (BCS) class II or IV, both characterized by very poor aqueous solubility. This leads to a higher demand for techniques that improve solubility in water-based media. This study aims to compile and present a comprehensive and detailed assessment of cocrystals and nano-cocrystals. It emphasizes the importance of in-depth research into nano-cocrystals to gather more raw data, which will support the eventual translation of nano-cocrystals into clinical use and market approval. Cocrystal technology has been used to enhance various physicochemical parameters, including stability, solubility, and bioavailability. Nano-cocrystallization is a new emerging technique that combines the benefits of cocrystallization with nanosizing, resulting in cocrystals with improved physicochemical properties and increased surface area due to nanoscale particles. These methods not only enhance aqueous solubility but have also been shown to directly increase the dissolution rate and improve the dissolution profile of drug substances. A literature review was conducted using PubMed, Scopus, and patent databases. Cocrystals and multicomponent systems are discussed with an emphasis on their crystal structure, types and nature of bonds formed, and any significant variations or special characteristics are highlighted. This thorough review offers an overview of cocrystals and nano-cocrystals, outlining the cocrystallization process and various methods for formulation and characterization. It also covers the selection process for coformers, including new computational, AI, and machine learning techniques for screening. The review introduces nano-cocrystals, describing their synthesis methods and benefits. It discusses polymorphism in both cocrystals and nano-cocrystals, and compares cocrystals as a way to improve solubility. Additionally, it evaluates their different applications and clinical outcomes. The discussion points out that the limited research on nano-cocrystals hinders their translation into industrial and clinical use. In contrast, cocrystals, despite some barriers, have achieved notable commercial success.
大多数现代药物口服生物利用度差主要是由水溶性差引起的。大多数新化学实体（NCEs）以及近40%的市售药物属于生物药剂学分类系统（BCS）中的II类或IV类，其特点均为水溶性极差。这就对提高在水基介质中溶解度的技术提出了更高的要求。本研究旨在对共晶体和纳米共晶体进行全面而详细的评估。强调了深入研究纳米共晶体以收集更多原始数据的重要性，这将支持纳米共晶体最终转化为临床应用并获得市场批准。共晶体技术已被用于改善各种物理化学参数，包括稳定性、溶解度和生物利用度。纳米共结晶是一种新兴技术，它将共结晶的优点与纳米尺寸相结合，由于纳米级颗粒，形成了具有改善的物理化学性质和增加表面积的共晶体。这些方法不仅提高了水溶性，还被证明能直接提高药物的溶解速率并改善其溶出曲线。使用PubMed、Scopus和专利数据库进行了文献综述。讨论了共晶体和多组分系统，重点介绍了它们的晶体结构、形成的键的类型和性质，并突出了任何显著的变化或特殊特征。这一全面的综述概述了共晶体和纳米共晶体，概述了共结晶过程以及各种制剂和表征方法。它还涵盖了共形成剂的选择过程，包括用于筛选的新的计算、人工智能和机器学习技术。该综述介绍了纳米共晶体，描述了它们的合成方法和优点。讨论了共晶体和纳米共晶体中的多晶型现象，并比较了共晶体作为提高溶解度的一种方法。此外，还评估了它们的不同应用和临床结果。讨论指出，对纳米共晶体的研究有限阻碍了它们转化为工业和临床应用。相比之下，共晶体尽管存在一些障碍，但已取得了显著的商业成功。
