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Uso de PBPK para Simular Perfiles de Disolución Predictivos Biológicamente para Inyectables de Acción Prolongada:

Hannah Cleary^1,2, Nikoletta Fotaki³, Tim Persoons^2,4

¹EPSRC-Research Ireland Centre for Doctoral Training in Transformative Pharmaceutical Technologies, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland.

CPT: pharmacometrics & systems pharmacology

|February 19, 2026

Resumen

El desarrollo de pruebas de disolución predictivas biológicamente para inyectables de acción prolongada (LAI) requiere la comprensión de los parámetros in vivo. Los modelos farmacocinéticos basados en modelos fisiológicos (PBPK) simularon una disolución más lenta de LAI, guiando el desarrollo de pruebas in vitro.

Área de la Ciencia:

Ciencias Farmacéuticas; Farmacocinética; Liberación de Fármacos

Sus antecedentes:

Los inyectables de acción prolongada (LAI) ofrecen una mejor adherencia a la medicación y una exposición sostenida al fármaco.
Las pruebas de disolución in vitro predictivas biológicamente son cruciales para el desarrollo de formulaciones y el control de calidad de LAI.
La comprensión de los mecanismos de disolución in vivo es esencial para el desarrollo de pruebas in vitro precisas.

Objetivo del estudio:

Cuantificar el impacto de los parámetros in vivo (atributos críticos de biodisponibilidad) en la disolución de LAI.
Utilizar modelos farmacocinéticos basados en modelos fisiológicos (PBPK) para simular perfiles de disolución de LAI.
Establecer un espacio de diseño para métodos de prueba de disolución in vitro predictivos biológicamente para LAI.

Principales métodos:

Desarrollo de modelos PBPK para LAI de acetato de metilprednisolona.
Simulación de perfiles de disolución in vivo variando atributos críticos de biodisponibilidad (tamaño de partícula, solubilidad, espesor de la capa de difusión, coeficiente de difusión, volumen del depósito).
Comparación de la disolución in vivo simulada con datos in vitro existentes.

Principales resultados:

Los perfiles de disolución simulados in vivo mostraron una liberación de fármaco significativamente más lenta (80-100% disuelto durante 1200 horas) en comparación con las pruebas in vitro estándar (aproximadamente 90% disuelto en 90 minutos).
El rendimiento del modelo varió según la fuente de los valores de los atributos (literatura vs. predicción).
El estudio identificó parámetros clave que influyen en la velocidad y el perfil de disolución.

Conclusiones:

Se necesitan condiciones de disolución in vitro que imiten bajas velocidades de fluido (mayor tamaño de partícula efectivo, espesor de la capa de difusión) para pruebas predictivas biológicamente.
El modelado PBPK con rangos plausibles de valores de atributos puede simular perfiles de disolución objetivo.
Este enfoque ayuda en el desarrollo de métodos de prueba de disolución in vitro robustos para formulaciones de LAI.

Palabras clave:

atributos de biodisponibilidad pruebas de rendimiento predictivas biológicamente pruebas de disolución inyección de acción prolongada modelado farmacocinético

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