Formulation Strategy of BCS-II Drugs by Coupling Mechanistic In-Vitro and Nonclinical In-Vivo Data with PBPK: Fundamentals of Absorption-Dissolution to Parameterization of Modelling and Simulation

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Shriya V A, Usha Y. Nayak, Muddukrishna Badamane Sathyanarayana, Bhim Bahadur Chaudhari, Krishnamurthy Bhat
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引用次数: 0

Abstract

BCS class II candidates pose challenges in drug development due to their low solubility and permeability. Researchers have explored various techniques; co-amorphous and solid dispersion are major approaches to enhance in-vitro drug solubility and dissolution. However, in-vivo oral bioavailability remains challenging. Physiologically based pharmacokinetic (PBPK) modeling with a detailed understanding of drug absorption, distribution, metabolism, and excretion (ADME) using a mechanistic approach is emerging. This review summarizes the fundamentals of the PBPK, dissolution—absorption models, parameterization of oral absorption for BCS class II drugs, and provides information about newly emerging artificial intelligence/machine learning (AI/ML) linked PBPK approaches with their advantages, disadvantages, challenges and areas of further exploration. Additionally, the fully integrated workflow for formulation design for investigational new drugs (INDs) and virtual bioequivalence for generic molecules falling under BCS-II are discussed.

Graphical Abstract

将体外机理和体内非临床数据与 PBPK 结合起来,制定 BCS-II 药物的配方策略:从吸收-溶解基础到建模和模拟参数化
由于BCS II类候选物质的低溶解度和渗透性,它们在药物开发中构成了挑战。研究人员已经探索了各种技术;共非晶分散体和固体分散体是提高体外药物溶解度和溶出度的主要途径。然而,体内口服生物利用度仍然具有挑战性。基于生理的药代动力学(PBPK)模型正在兴起,该模型详细了解了药物吸收、分布、代谢和排泄(ADME)的机制方法。本文综述了PBPK的基本原理、溶出-吸收模型、BCS II类药物口服吸收的参数化,并提供了新兴的人工智能/机器学习(AI/ML)相关PBPK方法的优点、缺点、挑战和进一步探索的领域。此外,本文还讨论了在研新药(INDs)配方设计的完全集成工作流和BCS-II下仿制药分子的虚拟生物等效性。图形抽象
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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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