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

Publication date: Available online 19 February 2020Source: Journal of Pharmaceutical AnalysisAuthor(s): Vijayabhaskar Veeravalli, Hanumanth Srikanth Cheruvu, Pratima Srivastava, Lakshmi Mohan Vamsi MadgulaAbstractFormulation/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 would be comprehe...
Source: Journal of Pharmaceutical Analysis - Category: Drugs & Pharmacology Source Type: research