An integrated biophysical model for predicting the clinical pharmacokinetics of transdermally delivered compounds

Somayaji, Mahadevabharath R.; Das, Debarun; Garimella, Harsha T.; German, Carrie; Przekwas, Andrzej; Simon, Laurent

doi:10.1016/j.ejps.2021.105924

Cited by 10 publications

(2 citation statements)

References 172 publications

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“…Transdermal delivery of estradiol can provide a sustained release of the drug, which may lead to improved pain control and fewer side effects than oral administration. The design of transdermal drug delivery systems and the factors affecting drug permeation, bioavailability, and pharmacokinetics are important considerations in the development of these systems [ 43 ].…”

Section: Resultsmentioning

confidence: 99%

Advances in Transdermal Drug Delivery Systems: A Bibliometric and Patent Analysis

Cammarano,

Dello Iacono,

Meglio

et al. 2023

Pharmaceutics

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Transdermal drug delivery systems have become an intriguing research topic in healthcare technology and one of the most frequently developed pharmaceutical products in the global market. In recent years, researchers and pharmaceutical companies have made significant progress in developing new solutions in the field. This study sheds light on current trends, collaboration patterns, research hotspots, and emerging frontiers of transdermal drug delivery. Herein, a bibliometric and patent analysis of data recovered from Scopus and The Lens databases, respectively, is reported over the last 20 years. From 2000 to 2022, the annual global publications increased from 131 in 2000 to 659 in 2022. Researchers in the United States, China, and India produced the highest number of publications. Likewise, most patent applications have been filed in the USA, China, and Europe. The recovered patents are 7275, grouped into 2997 patent families, of which 314 were granted. This study could support the work of decision-makers, scientific managers, or scientists to create new business opportunities or save money, time, and intellectual capital, thereby defining when a research or technology project should be a priority or not.

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Section: Resultsmentioning

confidence: 99%

Advances in Transdermal Drug Delivery Systems: A Bibliometric and Patent Analysis

Cammarano,

Dello Iacono,

Meglio

et al. 2023

Pharmaceutics

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show abstract

“…However, both differences in human and animal physiology as well as ethical concerns over animal testing have spurred the development of in vitro and in silico methods to help assess dermal drug absorption. Recent advances in mechanistic model development, their acceptance, and potential role have resulted in advanced models available in the literature (Somayaji et al, 2021;Patel et al, 2022). To utilise these models for assessing the bioavailability of dermatological drug products, the development of mechanistic formulation models that can integrate data from in vitro characterisation studies is essential.…”

Section: Introductionmentioning

confidence: 99%

A mechanistic physiologically based model to assess the effect of study design and modified physiology on formulation safe space for virtual bioequivalence of dermatological drug products

2022

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Physiologically based pharmacokinetic (PBPK) models are widely accepted tools utilised to describe and predict drug pharmacokinetics (PK). This includes the use of dermal PBPK models at the regulatory level including virtual bioequivalence (VBE) studies. The current work considers the Topicort® Spray formulation, which contains 0.25% desoximetasone (DSM), as an example formulation. Quantitative formulation composition and in vitro permeation testing (IVPT) data were obtained from the public literature to develop a mechanistic model using the multi-phase, multi-layer (MPML) MechDermA IVPT module in the Simcyp Simulator. In vitro–in vivo extrapolation functionality was used to simulate in vivo PK for various scenarios and predict a ‘safe space’ for formulation bioequivalence using the VBE module. The potential effect of vasoconstriction, impaired barrier function, and various dosing scenarios on the formulation safe space was also assessed. The model predicted ‘safe space’ for formulation solubility suggesting that a 50% change in solubility may cause bio-in-equivalence, whereas viscosity could deviate by orders of magnitude and the formulation may still remain bioequivalent. Evaporation rate and fraction of volatile components showed some sensitivity, suggesting that large changes in the volume or composition of the volatile fraction could cause bio-in-equivalence. The tested dosing scenarios showed decreased sensitivity for all formulation parameters with a decreased dose. The relative formulation bioequivalence was insensitive to vasoconstriction, but the safe space became wider with decreased barrier function for all parameters, except viscosity that was unaffected.

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Microneedle Mediated Iontophoretic Delivery of Tofacitinib Citrate

et al. 2022

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Purpose To investigate in vitro transdermal delivery of tofacitinib citrate across human skin using microporation by microneedles and iontophoresis alone and in combination. Methods In vitro permeation studies were conducted using vertical Franz diffusion cells. Microneedles composed of polyvinyl alcohol and carboxymethyl cellulose were fabricated and successfully characterized using scanning electron microscopy. The microchannels created were further characterized using histology, dye binding study, scanning electron microscopy, and confocal microscopy studies. The effect of microporation on delivery of tofacitinib citrate was evaluated alone and in combination with iontophoresis. In addition, the effect of current density on iontophoretic delivery was also investigated. Results Total delivery of tofacitinib citrate via passive permeation was found out to be 11.04 ± 1 μg/sq.cm. Microporation with microneedles resulted in significant enhancement where a 28-fold increase in delivery of tofacitinib citrate was observed with a total delivery of 314.7±33.32 μg/sq.cm. The characterization studies confirmed the formation of microchannels in the skin where successful disruption of stratum corneum was observed after applying microneedles. Anodal iontophoresis at 0.1 and 0.5 mA/sq.cm showed a total delivery of 18.56 μg/sq.cm and 62.07 μg/sq.cm, respectively. A combination of microneedle and iontophoresis at 0.5 mA/sq.cm showed the highest total delivery of 566.59 μg/sq.cm demonstrating a synergistic effect. A sharp increase in transdermal flux was observed for a combination of microneedles and iontophoresis. Conclusion This study demonstrates the use of microneedles and iontophoresis to deliver a therapeutic dose of tofacitinib citrate via transdermal route.

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An integrated biophysical model for predicting the clinical pharmacokinetics of transdermally delivered compounds

Cited by 10 publications

References 172 publications

Advances in Transdermal Drug Delivery Systems: A Bibliometric and Patent Analysis

Advances in Transdermal Drug Delivery Systems: A Bibliometric and Patent Analysis

A mechanistic physiologically based model to assess the effect of study design and modified physiology on formulation safe space for virtual bioequivalence of dermatological drug products

Microneedle Mediated Iontophoretic Delivery of Tofacitinib Citrate

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