Exploring Experimental and Statistical Approaches to Control Oversensitivity of In Vitro Permeability to Excipient Effects

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dc.article.number1110
dc.catalogadorpva
dc.contributor.authorGarcía Alcalde, Mauricio Andrés
dc.contributor.authorAceituno, Alexis
dc.contributor.authorDíaz Santana, Nicole Belén
dc.contributor.authorTapia Rivera, Eduardo Moisés
dc.contributor.authorContreras Valverde, Danae Valentina
dc.contributor.authorLópez Lagos, Constanza Beatriz Estefanía
dc.contributor.authorSánchez, Virginia
dc.contributor.authorGonzález, Pablo M.
dc.date.accessioned2025-09-03T19:53:23Z
dc.date.available2025-09-03T19:53:23Z
dc.date.issued2025
dc.description.abstractBackground/Objectives: The static in vitro permeability assay based on cell monolayers has been widely used in the pharmaceutical industry and recognized by regulatory agencies as a surrogate method for BCS classification. However, the application of such an experiment to study the effects of formulations is limited by the oversensitivity to the excipient effect on drug permeability. In this article, we studied the effects of common excipients on the permeability of moderately and poorly absorbed model compounds across cell monolayers, using two approaches to control said oversensitivity. Methods: Drug permeability across MDCK-wt was assessed in the absence (control) or presence (treatment) of excipients, using minoxidil as a high-permeability marker. The effects of excipients were parameterized as a permeability ratio (PR = treatment/control) without or with normalization (nPR) by minoxidil permeability. Metrics were compared by either ANOVA (p < 0.01) or confidence intervals (CI90, as per bioequivalence metrics) to identify excipient effects. Results: Acyclovir and hydrochlorothiazide showed the highest and lowest number of interactions, respectively. The most impactful excipients were sodium lauryl sulfate, microcrystalline cellulose, and sodium starch glycolate. Unexpectedly, nPR increased the number of excipient effects across model drugs (19 vs. 21). Alternatively, the CI90 approach was more sensitive than ANOVA in identifying excipient effects (41 vs. 32). Conclusions: Minoxidil was not able to control the anticipated oversensitivity of cell-based permeability experiments. Meanwhile, ANOVA was overall able to reduce oversensitivity to excipient effects on drug permeability compared to CI90. Nonetheless, there might be a niche for CI90 analysis when comparing the performance of two formulations on the permeability of moderately and poorly absorbed drugs.
dc.fechaingreso.objetodigital2025-09-03
dc.format.extent19 páginas
dc.fuente.origenORCID
dc.identifier.doi10.3390/pharmaceutics17091110
dc.identifier.urihttps://doi.org/10.3390/pharmaceutics17091110
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/105548
dc.information.autorucEscuela de Química; García Alcalde, Mauricio Andrés; S/I; 181066
dc.information.autorucEscuela de Ingeniería; Díaz Santana, Nicole Belén; S/I; 185299
dc.information.autorucEscuela de Química; Tapia Rivera, Eduardo Moisés; S/I; 233949
dc.information.autorucEscuela de Química; Contreras Valverde, Danae Valentina; S/I; 223515
dc.information.autorucEscuela de Química; López Lagos, Constanza Beatriz Estefanía; S/I; 224423
dc.issue.numero9
dc.language.isoen
dc.nota.accesocontenido completo
dc.publisherMDPI
dc.revistaPharmaceutics
dc.rightsacceso abierto
dc.rights.licenseAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectPermeability
dc.subjectExcipient effect
dc.subjectMDCK-wt monolayers
dc.subjectStatistical comparison permeability
dc.subjectOral absorption
dc.subjectComparative permeability
dc.subjectCommon excipients
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleExploring Experimental and Statistical Approaches to Control Oversensitivity of In Vitro Permeability to Excipient Effects
dc.typeartículo
dc.volumen17
sipa.codpersvinculados181066
sipa.codpersvinculados185299
sipa.codpersvinculados233949
sipa.codpersvinculados223515
sipa.codpersvinculados224423
sipa.trazabilidadORCID;2025-09-01
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