Excipient Characterization

Good, David; Wu, Yongmei

doi:10.1002/9781118992432.ch1

Cited by 1 publication

(1 citation statement)

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“…The manufacturing process of many excipients might contain levels of reactive impurities (such as reducing sugar, aldehydes, peroxides, nitrites, organic acids, and metals), which might lead to incompatibilities with APIs in the formulations. 15 Pharmacokinetics/toxicokinetics of excipients is the study of absorption, distribution, metabolism, and excretion (ADME) of excipients in relation to their pharmacological/toxic effects. The chemical structure and chemical and physical properties of the excipients are to be examined first in hazard identification, as these may show possible toxicological issue.…”

Section: Introductionmentioning

confidence: 99%

In Silico Investigation of First-Pass Effect on Selected Small Molecule Excipients and Structural Dynamics of P-glycoprotein

Fatoki

Ibraheem

Awofisayo

et al. 2020

Bioinform Biol Insights

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In this study, the interaction of selected pharmaceutical excipients on the function of P-glycoprotein (P-gp) and activity of 6 cytochrome P450 (CYP) isoforms were computationally investigated. At binding free energy cut-off value of −5.0 kcal/mol, the result showed possible modulatory or inhibitory effect by cethyl alcohol on CPY3A4 and P-gp; cetyltrimethyl-ammonium bromide (CTAB) on CYP1A2 and P-gp; dibutyl sebacate on CYP2C9, CYP2E1, and P-gp; sodium caprylate on CYP1A2 and CYP3A4; while most of the tested excipients have good interaction with the cytochromes and P-gp. The predicted pharmacokinetics provided possible inhibitors of the CYPs and P-gp and suggested that aspartame and acetyl tributyl citrate may not permeate blood–brain barrier and not act as P-gp substrates. Target prediction for CTAB showed 100% and 35% probability of target to dynamin-1 (UniProt ID: Q05193) and histamine H3 receptor (UniProt ID: Q9Y5N1), respectively, whereas tricaprylin showed 40% probability of target to 5 Protein kinase C (UniProt IDs: P17252, Q02156, Q04759, P24723, and P05129). This study shows that synergistic effect of some excipients present in a drug formulation and multiple drugs administration is possible through modulation of CYPs activities and P-gp function, and this is crucial for consideration to mitigate toxicity in pediatric and adult populations.

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Section: Introductionmentioning

confidence: 99%