Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Campus for Research Excellence and Technological Enterprise, Singapore, 138602, Singapore.
Adv Mater. 2021 Jul;33(29):e2008618. doi: 10.1002/adma.202008618. Epub 2021 Jun 7.
Oral drug products have become indispensable in modern medicine because of their exceptional patient compliance. However, poor bioavailability of ubiquitous low-water-soluble active pharmaceutical ingredients (APIs) and lack of efficient oral drug formulations remain as significant challenges. Nanocrystalline formulations are an attractive route to increase API solubility, but typically require abrasive mechanical milling and several processing steps to create an oral dosage form. Using the dual amphiphilic and thermoresponsive properties of methylcellulose (MC), a new thermogelling nanoemulsion and a facile thermal dripping method are developed for efficient formulation of composite particles with the MC matrix embedded with precisely controlled API nanocrystals. Moreover, a fast and tunable release performance is achieved with the combination of a fast-eroding MC matrix and fast-dissolving API nanocrystals. Using the versatile thermal processing approach, the thermogelling nanoemulsion is easily formulated into a wide variety of dosage forms (nanoparticle suspension, drug tablet, and oral thin film) in a manner that avoids nanomilling. Overall, the proposed thermogelling nanoemulsion platform not only broadens the applications of thermoresponsive nanoemulsions but also shows great promise for more efficient formulation of oral drug products with high quality and tunable fast release.
口服药物制剂在现代医学中不可或缺，因为它们具有出色的患者顺应性。然而，普遍存在的低水溶性活性药物成分（APIs）的生物利用度差和缺乏有效的口服药物制剂仍然是重大挑战。纳米晶体制剂是提高 API 溶解度的一种有吸引力的途径，但通常需要研磨和几个处理步骤来创建口服剂型。利用甲基纤维素（MC）的双重两亲性和温度响应特性，开发了一种新的温敏纳米乳液和一种简便的热滴法，用于高效制备 MC 基质中嵌入精确控制的 API 纳米晶体的复合颗粒。此外，通过快速侵蚀的 MC 基质和快速溶解的 API 纳米晶体的结合，实现了快速且可调的释放性能。使用多功能热加工方法，温敏纳米乳液可以很容易地以避免纳米研磨的方式配制成各种剂型（纳米颗粒混悬剂、药物片剂和口服薄膜）。总的来说，所提出的温敏纳米乳液平台不仅拓宽了温度响应纳米乳液的应用范围，而且对于具有高质量和可调快速释放的更有效的口服药物制剂的制剂也显示出巨大的潜力。
