A Comparative Evaluation of Desoximetasone Cream and Ointment Formulations Using Experiments and In Silico Modeling

The administration of therapeutic drugs through dermal routes, such as creams and ointments, has emerged as an increasingly popular alternative to traditional delivery methods, such as tablets and injections. In the context of drug development, it is crucial to identify the optimal doses and delivery routes that ensure successful outcomes. Physiologically based pharmacokinetic (PBPK) models have been proposed to simulate drug delivery and optimize drug formulations, but the calibration of these models is challenging due to the multitude of variables involved and limited experimental data. One significant research gap that this article addresses is the need for more efficient and accurate methods for calibrating PBPK models for dermal drug delivery. This manuscript presents a novel approach and an integrated dermal drug delivery model to address this gap that leverages virtual in vitro release (IVRT) and permeation (IVPT) testing data to optimize mechanistic models. The proposed approach was demonstrated through a study involving Desoximetasone cream and ointment formulations, where the release kinetics and permeation profiles of Desoximetasone were determined experimentally, and a computational model was created to simulate the results. The experimental studies showed that, even though the cumulative permeation of Desoximetasone at the end of the permeation study was comparable, there was a significant difference seen in the lag time in the permeation of Desoximetasone between the cream and ointment. Additionally, there was a significant difference seen in the amount of Desoximetasone permeated through human cadaver skin at early time points when the cream and ointment were compared. The computational model was optimized and validated, suggesting that this approach has the potential to bridge the existing research gap by improving the accuracy and efficiency of drug development processes. The model results show a good fit between the experimental data and model predictions. During the model optimization process, it became evident that there was variability in both the permeability and the partition coefficient within the stratum corneum. This variability had a significant and noteworthy influence on the overall performance of the model, especially when it came to its capacity to differentiate between cream and ointment formulations. Leveraging virtual models significantly aids the comprehension of drug release and permeation, mitigating the demanding data requirements. The use of virtual IVRT and IVPT data can accelerate the calibration of PBPK models, streamline the selection of the appropriate doses, and optimize drug delivery. Moreover, this novel approach could potentially reduce the time and resources involved in drug development, thus making it more cost-effective and efficient.

Medienart:	E-Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:24
Enthalten in:	International journal of molecular sciences - 24(2023), 20 vom: 12. Okt.

Sprache:	Englisch

Beteiligte Personen:	Matharoo, Namrata S [VerfasserIn] Garimella, Harsha T [VerfasserIn] German, Carrie [VerfasserIn] Przekwas, Andrzej J [VerfasserIn] Michniak-Kohn, Bozena [VerfasserIn]

Links:	Volltext

Themen:	4E07GXB7AU Dermal kinetics Desoximetasone Drug release Formulation IVPT IVRT In silico modeling Journal Article Modelling and simulation Ointments PBPK PKPD Permeation Pharmacology Topical Transdermal

Anmerkungen:	Date Completed 30.10.2023 Date Revised 10.02.2024 published: Electronic Citation Status MEDLINE

doi:	10.3390/ijms242015118

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM363868186