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.

制剂/药用辅料在配制候选药物中发挥着重要作用，其目标是易于给药、靶向递送和完全可用性。药物制剂中使用的许多赋形剂在临床前药物发现中都是孤立的。这些孤儿赋形剂可以增强高亲脂性化合物的配制性。此外，当在 LD ₅₀值以下使用时，它们在临床前物种中是安全的。然而，当赋形剂用于配制具有不同物理化学性质的化合物时，它们会通过其生物分析基质效应来调节研究结果，从而带来挑战。赋形剂总是存在于研究样品中而不是校准曲线标准品中，导致暴露量的高估/低估。因此，需要重新审视赋形剂引起基质效应的机制以及消除这些效应的策略。此外，制剂赋形剂通过调节药物代谢酶和药物转运蛋白的途径引起药物相互作用。尽管不可能消除辅料驱动的相互作用，但始终建议您了解这些相互作用并应用这些知识从研究结果中得出有意义的结论。在这篇综述中，我们将全面讨论a）在临床前制剂中具有更广泛应用的孤儿辅料，b）生物分析基质效应和减轻这些影响的可能方法，以及c）辅料驱动的药物相互作用和减轻药物相互作用影响的策略。