Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Pharmaceutics
2023 Jun 11;156:. doi: 10.3390/pharmaceutics15061707.
Show Gene links
Show Anatomy links
Metamorphosis of Topical Semisolid Products-Understanding the Role of Rheological Properties in Drug Permeation under the "in Use" Condition.
Jin X
,
Alavi SE
,
Shafiee A
,
Leite-Silva VR
,
Khosrotehrani K
,
Mohammed Y
.
Abstract
When developing topical semisolid products, it is crucial to consider the metamorphosis of the formulation under the "in use" condition. Numerous critical quality characteristics, including rheological properties, thermodynamic activity, particle size, globule size, and the rate/extent of drug release/permeation, can be altered during this process. This study aimed to use lidocaine as a model drug to establish a connection between the evaporation and change of rheological properties and the permeation of active pharmaceutical ingredients (APIs) in topical semisolid products under the "in use" condition. The evaporation rate of the lidocaine cream formulation was calculated by measuring the weight loss and heat flow of the sample using DSC/TGA. Changes in rheological properties due to metamorphosis were assessed and predicted using the Carreau-Yasuda model. The impact of solvent evaporation on a drug's permeability was studied by in vitro permeation testing (IVPT) using occluded and unconcluded cells. Overall, it was found that the viscosity and elastic modulus of prepared lidocaine cream gradually increased with the time of evaporation as a result of the aggregation of carbopol micelles and the crystallization of API after application. Compared to occluded cells, the permeability of lidocaine for formulation F1 (2.5% lidocaine) in unoccluded cells decreased by 32.4%. This was believed to be the result of increasing viscosity and crystallization of lidocaine instead of depletion of API from the applied dose, which was confirmed by formulation F2 with a higher content of API (5% lidocaine) showing a similar pattern, i.e., a 49.7% reduction of permeability after 4 h of study. To the best of our knowledge, this is the first study to simultaneously demonstrate the rheological change of a topical semisolid formulation during volatile solvent evaporation, resulting in a concurrent decrease in the permeability of API, which provides mathematical modelers with the necessary background to build complex models that incorporate evaporation, viscosity, and drug permeation in the simulation once at a time.
Arora,
Mechanistic Modeling of In Vitro Skin Permeation and Extrapolation to In Vivo for Topically Applied Metronidazole Drug Products Using a Physiologically Based Pharmacokinetic Model.
2022, Pubmed
Arora,
Mechanistic Modeling of In Vitro Skin Permeation and Extrapolation to In Vivo for Topically Applied Metronidazole Drug Products Using a Physiologically Based Pharmacokinetic Model.
2022,
Pubmed
BARRETT,
THE INFLUENCE OF VEHICLES ON SKIN PENETRATION.
1964,
Pubmed
Belsey,
Evaluation of drug delivery to intact and porated skin by coherent Raman scattering and fluorescence microscopies.
2014,
Pubmed
Buhse,
Topical drug classification.
2005,
Pubmed
Chen,
Evaluating Molecular Properties Involved in Transport of Small Molecules in Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin Permeability.
2018,
Pubmed
Coldman,
Enhancement of percutaneous absorption by the use of volatile: nonvolatile systems as vehicles.
1969,
Pubmed
Cross,
Can increasing the viscosity of formulations be used to reduce the human skin penetration of the sunscreen oxybenzone?
2001,
Pubmed
Dabbaghi,
Viscoelastic and Deformation Characteristics of Structurally Different Commercial Topical Systems.
2021,
Pubmed
Geng,
Investigation of the Evaporation Rate of Water from Colloidal Unimolecular Polymer (CUP) Systems by Isothermal TGA.
2020,
Pubmed
Hadgraft,
Drug crystallization - implications for topical and transdermal delivery.
2016,
Pubmed
Haq,
Solubility-physicochemical-thermodynamic theory of penetration enhancer mechanism of action.
2020,
Pubmed
Hummer,
Optimization of topical formulations using a combination of in vitro methods to quantify the transdermal passive diffusion of drugs.
2022,
Pubmed
Hunter,
INFLUENCE OF TOPICALLY APPLIED MENTHOL COOLING GEL ON SOFT TISSUE THERMODYNAMICS AND ARTERIAL AND CUTANEOUS BLOOD FLOW AT REST.
2018,
Pubmed
Jin,
Topical Semisolid Products-Understanding the Impact of Metamorphosis on Skin Penetration and Physicochemical Properties.
2022,
Pubmed
Jung,
Application of Confocal Raman Microscopy for the Characterization of Topical Semisolid Formulations and their Penetration into Human Skin Ex Vivo.
2022,
Pubmed
KLIGMAN,
PREPARATION OF ISOLATED SHEETS OF HUMAN STRATUM CORNEUM.
1963,
Pubmed
Kamal,
Identification of critical formulation parameters affecting the in vitro release, permeation, and rheological properties of the acyclovir topical cream.
2020,
Pubmed
Kang,
Formulation and efficacy studies of new topical anesthetic creams.
2003,
Pubmed
Li,
Correlation between rheological properties, in vitro release, and percutaneous permeation of tetrahydropalmatine.
2011,
Pubmed
Miranda,
Quality and equivalence of topical products: A critical appraisal.
2020,
Pubmed
Mohammed,
Advances and future perspectives in epithelial drug delivery.
2022,
Pubmed
Namjoshi,
Quality by Design: Development of the Quality Target Product Profile (QTPP) for Semisolid Topical Products.
2020,
Pubmed
Park,
Rheological evaluation of petroleum jelly as a base material in ointment and cream formulations: steady shear flow behavior.
2010,
Pubmed
Roberts,
Topical drug delivery: History, percutaneous absorption, and product development.
2021,
Pubmed
Roberts,
Percutaneous absorption of topically applied NSAIDS and other compounds: role of solute properties, skin physiology and delivery systems.
1999,
Pubmed
Seo,
In vitro skin absorption tests of three types of parabens using a Franz diffusion cell.
2017,
Pubmed
Shin,
Cutaneous Pharmacokinetics of Acyclovir Cream 5% Products: Evaluating Bioequivalence with an In Vitro Permeation Test and an Adaptation of Scaled Average Bioequivalence.
2020,
Pubmed
Simões,
Progressing Towards the Sustainable Development of Cream Formulations.
2020,
Pubmed
Surber,
Metamorphosis of Vehicles: Mechanisms and Opportunities.
2018,
Pubmed
Welin-Berger,
The effect of rheological behaviour of a topical anaesthetic formulation on the release and permeation rates of the active compound.
2001,
Pubmed
Xu,
The comparison of rheological properties of aqueous welan gum and xanthan gum solutions.
2013,
Pubmed
Yang,
The molecular design of drug-ionic liquids for transdermal drug delivery: Mechanistic study of counterions structure on complex formation and skin permeation.
2021,
Pubmed
