University of Pécs, Institute of Pharmaceutical Technology and Biopharmacy, Pécs, Hungary.
University of Pécs, Institute of Pharmaceutical Technology and Biopharmacy, Pécs, Hungary.
Int J Pharm. 2019 Mar 10;558:319-327. doi: 10.1016/j.ijpharm.2019.01.007. Epub 2019 Jan 14.
Pharmaceutical co-crystals present an opportunity to improve the solubility of conventional active pharmaceutical ingredients (APIs). Despite advances in co-crystal screening, the rational design of even the chemically simplest co-crystals remains challenging. Hansen solubility parameters (HSPs) have previously been used as a tool to predict co-crystal formation using only the chemical structure. The aim of this study was to validate the use of HSPs as a tool to predict co-crystal formation, analyse its limitations and examine the previously set Δδ inclusion cut-off value. A total of 109 co-formers of carbamazepine, caffeine and theophylline were used as a training set. Sixteen different descriptors were examined. An additional 72 co-formers of piroxicam and nicotinamide were used to test the methods and new cut-off values. The established cut-off value (8.18 MP) despite being similar to the previously reported value (7 MP), offered no real advantage over the previously reported value. Our results suggest the use of the modified radius (Ra) method of calculating the solubility difference, which had higher sensitivity of 90% compared to 86% for the previously reported method and cut-off value to indicate co-crystal formation as well as a lower miss and false omission rates.
药物共晶为提高传统活性药物成分（API）的溶解度提供了机会。尽管共晶筛选取得了进展，但即使是最简单的共晶的合理设计仍然具有挑战性。Hansen 溶解度参数（HSP）以前曾被用作仅使用化学结构预测共晶形成的工具。本研究的目的是验证 HSP 作为预测共晶形成的工具的使用，分析其局限性，并检验先前设定的Δδ包含截止值。使用了 109 种卡马西平、咖啡因和茶碱的共晶形成剂作为训练集。检查了十六种不同的描述符。还使用了 72 种吡罗昔康和烟酰胺的共晶形成剂来测试方法和新的截止值。尽管建立的截止值（8.18 MP）与之前报道的值（7 MP）相似，但与之前报道的值相比，并没有真正的优势。我们的结果表明，使用改进的半径（Ra）方法计算溶解度差异具有更高的灵敏度，为 90%，而之前报道的方法和截止值为 86%，可指示共晶形成，以及更低的漏诊和假阴性率。
