Praziquantel (PZQ) is an anthelmintic drug with low solubility, therefore cocrystallization and particle size reduction is desirable to improve bioavailability. In this study, a PZQ-malonic acid cocrystal was micronized by rapid expansion of supercritical solution (RESS). Due to low solubility in scCO2, four cosolvents were screened as RESS modifiers. While addition of acetone or THF yielded mixtures of PZQ and its cocrystal, MeOH and EtOH produced pure cocrystal. Impact of pressure (15–30 MPa), temperature (35–55 °C), and cosolvent loading (3–10 volumes) on phase-purity, yield, and particle size were investigated. Adding cosolvent to RESS facilitated dissolution of cocrystal formers in scCO2 and crystallization of the cocrystal with yields up to 68.5 wt% and particle size as low as 600 nm. Results show that for APIs with low solubility in scCO2, cosolvent-modified RESS is a suitable approach for simultaneous crystallization and micronization.

中文翻译：

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溶剂选择和 RESS 加工条件对超临界 CO2 中吡喹酮-丙二酸共晶形成的影响


吡喹酮 （PZQ） 是一种溶解度低的驱虫药，因此共结晶和减小粒径是提高生物利用度的理想选择。在本研究中，通过超临界溶液 （RESS） 的快速膨胀对 PZQ-丙二酸共晶进行微粉化。由于在 scCO2 中的溶解度低，筛选出 4 种助溶剂作为 RESS 改性剂。虽然添加丙酮或 THF 会产生 PZQ 及其共晶体的混合物，但 MeOH 和 EtOH 会产生纯共晶体。研究了压力 （15–30 MPa）、温度 （35–55 °C） 和助溶剂负载量（3–10 体积）对相纯度、产率和粒径的影响。向 RESS 中添加助溶剂有助于共晶形成剂在 scCO2 中的溶解和共晶结晶，产率高达 68.5 wt%，粒径低至 600 nm。结果表明，对于在 scCO2 中溶解度低的 API，助溶剂改性的 RESS 是同时结晶和微粉化的合适方法。