School of Chemical and Bioprocess Engineering, University College Dublin, Dublin 4, Ireland; SSPC, The SFI Research Centre for Pharmaceuticals, School of Chemical and Bioprocess Engineering, University College Dublin, Dublin 4, Ireland; EPSRC-SFI Centre for Doctoral Training in Transformative Pharmaceutical Technologies, Ireland.
EPSRC-SFI Centre for Doctoral Training in Transformative Pharmaceutical Technologies, Ireland; SSPC, The SFI Research Centre for Pharmaceuticals, School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin 2, Ireland.
Int J Pharm. 2024 Dec 25;667(Pt A):124878. doi: 10.1016/j.ijpharm.2024.124878. Epub 2024 Nov 2.
Active Pharmaceutical Ingredient-Ionic liquids (API-ILs) have the potential to improve the bioavailability of BCS Class IV Drugs. However, the problematic physical handling properties of room temperature API-ILs have impaired clinical and commercial exploitation to date. Lipid-based formulations (LBFs) are used to improve the absorption of drugs with limited bioavailability. Nonetheless, LBFs face limitations such as low drug loading capacity and sub-par physical stability. A platform for transforming API-ILs into solid forms at high loadings via spray encapsulation with polymers has been developed and previously demonstrated for hydrophilic API-ILs. The current work demonstrates that this platform technology can be applied to a lipophilic API-IL of the BCS Class IV API, chlorpromazine, and to multi-component solutions comprising API-IL and a LBF. Furthermore, solidification of a type IIIB, liquid LBF was achieved via spray encapsulation with cellulose- and methacrylate- based polymers for the first time. The spray-encapsulated formulations had excellent physical handling properties, and successfully eluted the API-IL in aqueous media. The chlorpromazine release profiles from the API-IL, the API-IL containing LBF, and the solidified formulations, were evaluated in vitro using phosphate buffer (pH 6.8) and fasted state simulated intestinal fluid (FaSSIF). Spray-encapsulated formulations exhibited improved release profiles compared to the liquid formulations. Overall, these findings indicate that phase-separated, polymeric, solid formulations of liquid API forms represent a promising platform technology for developing oral solid dosage forms of poorly bioavailable drugs.
活性药物成分-离子液体（API-ILs）有可能提高 BCS 分类 IV 药物的生物利用度。然而，室温下 API-ILs 的物理处理性能问题迄今阻碍了其临床和商业开发。基于脂质的制剂（LBFs）用于提高生物利用度有限的药物的吸收。尽管如此，LBFs 面临着诸如载药量低和物理稳定性不佳等限制。已经开发了一种通过聚合物喷雾包封将 API-IL 转化为高负载固体形式的平台，并已针对亲水性 API-IL 进行了先前的演示。目前的工作表明，该平台技术可应用于 BCS 分类 IV API 氯丙嗪的亲脂性 API-IL 以及包含 API-IL 和 LBF 的多组分溶液。此外，首次通过纤维素和甲基丙烯酸酯基聚合物的喷雾包封成功实现了 IIIB 型液态 LBF 的固化。喷雾包封的制剂具有出色的物理处理性能，并成功地在水性介质中洗脱 API-IL。使用磷酸盐缓冲液（pH 6.8）和空腹模拟肠液（FaSSIF）在体外评估了 API-IL、含有 API-IL 的 LBF 和固化制剂中的氯丙嗪释放曲线。与液态制剂相比，喷雾包封的制剂表现出改善的释放曲线。总的来说，这些发现表明，液体制剂的相分离、聚合、固态制剂代表了开发生物利用度差的药物口服固体制剂的有前途的平台技术。
