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Related Concept Videos

Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

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Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
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Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence01:27

Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence

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Changes in polymorphic forms can significantly influence the bioavailability of poorly soluble drugs. Although the FDA defines pharmaceutical equivalence based on having the same active ingredient, dosage form, and route of administration, it does not automatically disqualify products with different polymorphic forms. This means two products with different polymorphs can still be deemed pharmaceutically equivalent. However, polymorphic differences can affect properties like wettability,...
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Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

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The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
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Factors Influencing Drug Absorption: Pharmaceutical Parameters01:28

Factors Influencing Drug Absorption: Pharmaceutical Parameters

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Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
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Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism01:21

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism

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Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
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Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

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Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
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Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study
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Hidden Drug-Excipient Interaction by HPLC-MS/MS Analysis: Polysorbate 80 Enhances Nimodipine Systemic Exposure

Jiameng Qu1, Mingming Wang1, Yinfei Ran1

  • 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.

Biomedical Chromatography : BMC
|January 13, 2026
PubMed
Summary

Drug excipients like polysorbate 80 are not always inert. This study shows polysorbate 80 significantly increases nimodipine exposure by inhibiting its metabolism, challenging assumptions in drug development.

Keywords:
HPLC–MS/MSdrug–excipient interactionnimodipinepharmacokineticspolysorbate 80

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Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Pharmaceutical Sciences

Background:

  • Pharmaceutical excipients are traditionally viewed as inert carriers for active pharmaceutical ingredients.
  • Emerging evidence indicates significant drug-excipient interactions can impact therapeutic outcomes.
  • This study focuses on a potential interaction between nimodipine and polysorbate 80.

Purpose of the Study:

  • To investigate a novel pharmacokinetic interaction between nimodipine and polysorbate 80.
  • To challenge the conventional paradigm of excipient inertness.
  • To evaluate the impact of polysorbate 80 on nimodipine's systemic exposure and metabolism.

Main Methods:

  • Developed and validated a novel HPLC-MS/MS method for quantifying nimodipine and polysorbate 80.
  • Conducted pharmacokinetic studies in rats following co-administration.
  • Performed mechanistic investigations using rat liver microsomes to assess metabolic inhibition.

Main Results:

  • Polysorbate 80 significantly increased nimodipine's area under the curve (AUC) by 51.1%.
  • Co-administration decreased nimodipine clearance by 36.5% and prolonged its half-life by 16.1%.
  • Polysorbate 80 competitively inhibited nimodipine metabolism with an IC50 of 103.30 μmol/L.

Conclusions:

  • This study provides the first evidence of a clinically significant pharmacokinetic interaction between nimodipine and polysorbate 80.
  • The findings challenge the assumption of excipient inertness in pharmaceutical formulations.
  • Highlighting the importance of evaluating drug-excipient interactions in drug development and clinical practice.