Three-dimensional aspects of formulation excipients in drug discovery: a critical assessment on orphan excipients, matrix effects and drug interactions
| Autor: | Lakshmi Mohan Vamsi Madgula, Hanumanth Srikanth Cheruvu, Pratima Srivastava, Vijayabhaskar Veeravalli |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Drug
Matrix effects media_common.quotation_subject Pharmaceutical Science Excipient 02 engineering and technology Pharmacy 01 natural sciences Drug interactions Analytical Chemistry Pharmacokinetics Formulation development Drug Discovery Electrochemistry medicine Spectroscopy media_common Drug transport Review Paper Drug discovery Chemistry lcsh:RM1-950 010401 analytical chemistry 021001 nanoscience & nanotechnology Preclinical 0104 chemical sciences Drug metabolizing enzymes lcsh:Therapeutics. Pharmacology Bioanalysis Critical assessment Biochemical engineering 0210 nano-technology Formulation excipients medicine.drug |
| Zdroj: | Journal of Pharmaceutical Analysis, Vol 10, Iss 6, Pp 522-531 (2020) Journal of Pharmaceutical Analysis |
| ISSN: | 2095-1779 |
| DOI: | 10.1016/j.jpha.2020.02.007 |
| Popis: | 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. Graphical abstract Image 1 Highlights • Promising but orphanized formulation excipients were unveiled. • Matrix effects were explicitly discussed with mechanisms and mitigation strategies. • Excipient-drug interactions from a drug metabolism/transporter point of view were presented. • A comprehensive review article covering three-dimensional aspects of formulation excipients. |
| Databáze: | OpenAIRE |
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