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Advantages of the refined Developability Classification System (rDCS) in early discovery.
J Pharm Sci
December 2024
Janssen Research & Development, LLC, Discovery Pharmaceutics, San Diego, CA, USA.
Rat pharmacokinetic studies are commonly utilized in early discovery to support absorption, distribution, metabolism, and excretion optimization of active pharmaceutical ingredients (APIs). The aim of this work was to compare exposures from fit-for-purpose oral suspension and solution formulations in rats to guidance provided by the refined Developability Classification System (rDCS) with respect to identifying potential limits to oral absorption, formulation strategy selection, and to optimize oral bioavailability (BA). This investigation utilized six diverse APIs covering a large range of biorelevant solubility, metabolic stability, and oral BA in rats.
View Article and Find Full Text PDFBiowaiver monographs for immediate-release solid oral dosage forms: Voriconazole.
J Pharm Sci
November 2024
Fraunhofer Institute for Translational Medicine and Pharmacology, Frankfurt am Main, Germany. Electronic address:
According to the ICH M9 Guideline, the triazole antifungal voriconazole is a Biopharmaceutics Classification System (BCS) class II drug, being highly soluble at the highest dose strength but not at the highest single dose. Although the ICH M9 allows for consideration of BCS-based biowaivers in such cases, voriconazole does not meet the additional requirement of dose proportional pharmacokinetics (PK) over the therapeutic dose range. By contrast, if the classification were based on the FDA solubility criteria that were in place prior to ICH M9 (based on the highest dose strength), voriconazole would belong to BCS class I and thus qualify for the BCS-based biowaiver.
View Article and Find Full Text PDFBiowaiver monographs for immediate-release solid oral dosage forms: Lemborexant.
J Pharm Sci
October 2024
Fraunhofer Institute for Translational Medicine and Pharmacology, Frankfurt am Main, Germany. Electronic address:
Lemborexant is a dual orexin receptor antagonist assigned to class II of the Biopharmaceutics Classification System (BCS). Thus, the ICH M9 Guideline excludes immediate-release (IR) solid oral dosage forms containing lemborexant from BCS-based biowaivers, irrespective of their in vitro dissolution behavior. By contrast, classification of lemborexant according to the refined Developability Classification System (rDCS) falls into class I, indicating few biopharmaceutics risks.
View Article and Find Full Text PDFUsing the refined Developability Classification System (rDCS) to guide the design of oral formulations.
J Pharm Sci
December 2024
Fraunhofer Institute for Translational Medicine and Pharmacology, Frankfurt am Main, Germany. Electronic address:
The refined Developability Classification System (rDCS) provides a comprehensive animal-free approach for assessing biopharmaceutical risks associated with developing oral formulations. This work demonstrates practical application of a recently advanced rDCS framework guiding formulation design for six diverse active pharmaceutical ingredients (APIs) and compares rDCS classifications with those of the Biopharmaceutics Classification System (BCS). While the BCS assigns five of the APIs to class II/IV, indicating potentially unfavorable biopharmaceutical attributes, the rDCS provides a more nuanced risk assessment.
View Article and Find Full Text PDFBiorelevant dissolution and its concept have been widely accepted and further developed to meaningfully predict the bioperformance of oral drug products. Biorelevant methodologies have been applied to design and optimize oral formulations, to facilitate formulation bridging, and to predict the outcome of bioperformance by coupling the results with modeling. Yet, those methodologies have often been independently customized to align with specific aspects of the oral drug products being developed.
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