Using the refined Developability Classification System (rDCS) to guide the design of oral formulations.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Kristian Beran, Eline Hermans, René Holm, Kia Sepassi, Jennifer Dressman
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Abstract

The refined Developability Classification System (rDCS) provides a comprehensive animal-free approach for assessing biopharmaceutical risks associated with developing oral formulations. This work demonstrates practical application of a recently advanced rDCS framework guiding formulation design for six diverse active pharmaceutical ingredients (APIs) and compares rDCS classifications with those of the Biopharmaceutics Classification System (BCS). While the BCS assigns five of the APIs to class II/IV, indicating potentially unfavorable biopharmaceutical attributes, the rDCS provides a more nuanced risk assessment. Both BCS and rDCS assign acetaminophen to class I at therapeutic doses. Voriconazole and lemborexant (both BCS II) are classified in rDCS class I at therapeutic doses, indicating suitability for development as conventional oral formulations. Fedratinib is classified as BCS IV but the rDCS indicates a stratified risk (class I, IIa or IIb), depending on the relevance of supersaturation/precipitation in vivo. Voxelotor and istradefylline (both BCS II) belong to rDCS class IIb, requiring solubility enhancement to achieve adequate oral bioavailability. Comparing the rDCS analysis with literature on development and pharmacokinetics demonstrates that the rDCS reliably supports oral formulation design over a wide range of API characteristics, thus providing a strong foundation for guiding development.

使用改良的显影性分类系统 (rDCS) 指导口服制剂的设计。
完善的可开发性分类系统(rDCS)为评估与开发口服制剂相关的生物制药风险提供了一种全面的无动物实验方法。这项研究展示了最新先进的 rDCS 框架的实际应用,该框架可指导六种不同活性药物成分 (API) 的制剂设计,并将 rDCS 的分类与生物制药分类系统 (BCS) 的分类进行了比较。BCS 将其中五种原料药归入 II/IV 级,表明它们可能具有不利的生物制药属性,而 rDCS 则提供了更细致的风险评估。BCS 和 rDCS 都将对乙酰氨基酚定为治疗剂量下的 I 类。Voriconazole和lemborexant(均为BCS II)在治疗剂量下被归入rDCS I类,表明适合作为常规口服制剂进行开发。费拉替尼被归入 BCS IV 类,但 rDCS 表明存在分层风险(I、IIa 或 IIb 类),这取决于体内过饱和/沉淀的相关性。沃塞洛托和异曲非林(均为 BCS II)属于 rDCS IIb 级,需要提高溶解度以获得足够的口服生物利用度。将 rDCS 分析与有关开发和药代动力学的文献进行比较后发现,rDCS 可以可靠地支持各种原料药特性的口服制剂设计,从而为指导开发奠定了坚实的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
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