Three-dimensional aspects of formulation excipients in drug discovery:a critical assessment on orphan excipients,matrix effects and drug interactions

作     者：Vijayabhaskar Veeravalli Hanumanth Srikanth Cheruvu Pratima Srivastava Lakshmi Mohan Vamsi Madgula Vijayabhaskar Veeravalli;Hanumanth Srikanth Cheruvu;Pratima Srivastava;Lakshmi Mohan Vamsi Madgula

作者机构：Syngene International LimitedBiocon ParkSEZBommasandra Industrial Area-Phase-IV Bommasandra-Jigani Link RoadBangalore560099India GVK BIO Pvt LtdNacharamHyderabadTelangana500076India 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2020年第10卷第6期

页      面：522-531页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 0817[工学-化学工程与技术] 0703[理学-化学] 10[医学] 100602[医学-中西医结合临床] 0702[理学-物理学] 

主　　题：Formulation excipients Preclinical Drug discovery Matrix effects Drug interactions Bioanalysis Pharmacokinetics Formulation development 

摘      要：Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery.These orphan excipients could enhance formulatability of highly lipophilic compounds.Additionally,they are safe in preclinical species when used below the LD50 values.However,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix effects.Excipients invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of exposures.Thus,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited.Furthermore,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport proteins.Although it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results.In this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.