Design and Use of a Thermogelling Methylcellulose Nanoemulsion to Formulate Nanocrystalline Oral Dosage Forms
Design and Use of a Thermogelling Methylcellulose Nanoemulsion to Formulate Nanocrystalline Oral Dosage Forms
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DOI：
10.1002/adma.202008618
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发表时间：
2021-06-07
影响因子：
29.4
通讯作者：
Doyle, Patrick S.
中科院分区：
文献类型：
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作者：
Chen, Liang-Hsun;Doyle, Patrick S.
口服药物产品已成为现代医学中不可或缺的，因为它们具有出色的患者依从性。然而，普遍存在的低水溶性活性药物成分（API）的生物利用度差以及缺乏有效的口服药物制剂仍然是重大挑战。纳米晶体制剂是增加API溶解度的有吸引力的途径，但通常需要研磨机械研磨和几个加工步骤来产生口服剂型。利用甲基纤维素（MC）的双重两亲性和温敏性，开发了一种新的热凝胶化纳米乳液和一种简便的热滴注方法，用于有效地配制具有嵌入精确控制的API纳米晶体的MC基质的复合颗粒。此外，快速和可调的释放性能与快速侵蚀的MC基质和快速溶解的API纳米晶体的组合实现。使用通用的热加工方法，热凝胶化纳米乳剂可以以避免纳米研磨的方式容易地配制成各种剂型（纳米颗粒悬浮液、药物片剂和口服薄膜）。总的来说，所提出的热凝胶化纳米乳剂平台不仅拓宽了温敏纳米乳剂的应用，而且还显示出更有效地配制具有高质量和可调快速释放的口服药物产品的巨大前景。
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.