Effect of Lipophilicity on Microneedle-Mediated Iontophoretic Transdermal Delivery Across Human Skin In Vitro

Pawar, Kasturi; Smith, Forrest; Kolli, Chandra Sekhar; Babu, R. Jayachandra

doi:10.1002/jps.23694

Cited by 14 publications

(12 citation statements)

References 52 publications

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“…Many studies investigated the transdermal of atenolol using iontophoresis and chemical penetration enhancers [11][12][13][14][15]. Other studies evaluated the transdermal of atenolol such as using gel formulation, ethylene-vinyl acetate matrix or hydroxyl propyl methyl cellulose and ethyl cellulose matrix [16][17][18].…”

Section: Methodsmentioning

confidence: 99%

Transdermal of Atenolol via Microemulsions

et al. 2019

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Objective: Developing novel non-ionic microemulsions (MEs) for transdermal of atenolol as satisfactory alternative drug delivery systems for the oral route.Methods: Seven MEs were developed then checked for encapsulation of atenolol using Fourier Transform Infrared Spectroscopy (FTIRspectroscopy) (), isotropy, droplet sizes, rheological properties and transdermal flux using Franz diffusion cell. Furthermore, two MEs with best flux values were selected for bioavailability evaluation after transdermal application over rat's skin. Results:The results showed that the MEs complies with colloidal systems properties. Also, the developed MEs were stable throughout the study, ideal viscous systems with droplet sizes below 500 nm and isotropic. Besides, FTIR-spectra could reveal the structure of the MEs and encapsulation of atenolol inside the dispersed phase. Moreover, the flux values of atenolol in MEs through rat's skin varied with different factors such as atenolol concentration, MEs's composition, and zetapotential. The highest flux value of the developed systems was 243.5±16.3 µg. cm -2 . h -1 . Furthermore, the in vivo results showed that using the two tested microemulsions maximum plasma levels of atenolol 5.22±0.43 and 4.06±0.15 mg. ml -1 Conclusion:The developed microemulsions can be promise formulations for transdermal administration of atenolol as alternative for oral tablets. at 8.18 and 3.64 h respectively could be achieved. ) and Poloxyethylenesorbitan. Mono-oleate (TweenP ® P 80) were purchased from SIGMA (Lyon, France). Citric acid (CA) and Isopropyl Myristate (IPM) were purchased from Merck (Darmstadt, Germany). Instruments and methods Microemulsions (MEs) preparationMEs were prepared by the titration method [24]. Atenolol was dissolved in the hydrophilic phase composed of a mixture of water and ethanol or water, ethanol and DMSO. Two ml of IPM was added to atenolol solution. Either span 20 or mixture of span 20: tween 80 (3:2) were added dropwise with continuous stirring over magnetic stirrer to the lipophilic and hydrophilic phase mixture until a clear microemulsion was formed. The added amounts of surfactants were recorded. Compositions of the developed microemulsions are listed in table 1. Pseudo-ternary phase diagrams of microemulsion systemsA pseudo-ternary phase diagram was plotted to find the existence area of MEs. Another three-phase diagram for MEs with 100 mg atenolol was accomplished for testing the influence of atenolol on this area. Formulations were made using three components which are the hydrophilic phase, lipophilic phase, and surfactants. Each phase forms one face of the triangle. The formulations were made with fractions of the three components according to crossing points which formed by plotting three parallel lines to the three faces of the triangle. More formulations were made between the cross points on the border of MEs area. After mixing, clear and stable formulations were identified to be MEs [24]. Viscosity measurementAn electric Rheometer made by Anton Paar, universal tool, ...

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Section: Methodsmentioning

confidence: 99%

Transdermal of Atenolol via Microemulsions

et al. 2019

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“…Twice a day studies (drug application every 12 hours) were run for 24, 36, and 48 hours, resulting in two, three, and four drug applications, respectively. For solid MN studies, stainless steel Dermarollers® of 250 μm and 500 μm length were rolled across the diffusion area in four perpendicular lines, 5 times in each direction; this is similar to previously published methods (Pawar etal. 2013)To mimic the support of the tissue underlying the skin seen in vivo , the skin was placed on a polydimethylsiloxane polymer block during MN insertion.…”

Section: Methodsmentioning

confidence: 99%

Effect of dosing regimen and microneedle pretreatment on in vitro skin retention of topically applied beta-blockers

Kelchen

Brogden

2018

Biomed Microdevices

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Topical beta-blocker formulations are commonly used to treat infantile hemangiomas (IHs); however, the skin concentrations and drug permeation through the skin have not been quantified. Microneedles (MNs) may increase local skin concentrations, which could further enhance lesion clearance and improve dosing regimens. The objective of this study was to quantify skin concentrations and drug permeation of two beta-blockers, propranolol and timolol, in vitro after application to intact skin and skin pretreated with solid MNs of two lengths. Propranolol skin concentrations and drug permeation were significantly higher than timolol skin concentrations for all study conditions, which is likely due to the lipophilic nature of propranolol compared to the hydrophilicity of timolol. Propranolol skin concentrations were significantly influenced by dosing regimen, as skin concentrations increased with increasing drug application. Pretreatment of the skin with solid 250 μm and 500 μm length MNs increased local skin concentrations of timolol; propranolol skin concentrations did not significantly increase after MN pretreatment. Propranolol and timolol permeation through the skin increased after MN pretreatment with both MN lengths for both compounds. Taken together, solid MN pretreatment prior to application of topical timolol may be beneficial for deep or mixed IHs upon further optimization of the MN treatment paradigm.

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“…Typically, skin is pretreated with MNs, and then the drug of interest is applied with simultaneous iontophoresis for 4–6 hrs. [60], [61]. Two advantages of this delivery method are the ability to control the flux of drugs through the modulation of the applied current, as well as a reduction in the lag time needed for drugs to penetrate the skin [62].…”

Section: Techniques For Skin Permeabilizationmentioning

confidence: 99%

Skin permeabilization for transdermal drug delivery: recent advances and future prospects

Schoellhammer

Blankschtein

Langer³

2014

Expert Opinion on Drug Delivery

296

188

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Introduction Transdermal delivery has potential advantages over other routes of administration. It could reduce first-pass metabolism associated with oral delivery and is less painful than injections. However, the outermost layer of the skin, the stratum corneum (SC), limits passive diffusion to small lipophilic molecules. Therefore, methods are needed to safely permeabilize the SC so that ionic and larger molecules may be delivered transdermally. Areas Covered This review focuses on low-frequency sonophoresis, microneedles, electroporation and iontophoresis, and combinations of these methods to permeabilize the SC. The mechanisms of enhancement and developments in the last five years are discussed. Potentially high-impact applications, including protein delivery, vaccination, and sensing, are presented. Finally, commercial interest and clinical trials are discussed. Expert Opinion Not all permeabilization methods are appropriate for all applications. Focused studies into applications utilizing the advantages of each method are needed. The total dose and kinetics of delivery must be considered. Vaccination is one application where permeabilization methods could make an impact. Protein delivery and analyte sensing are also areas of potential impact, although the amount of material that can be delivered (or extracted) is of critical importance. Additional work on the miniaturization of these technologies will help to increase commercial interest.

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Effect of Lipophilicity on Microneedle-Mediated Iontophoretic Transdermal Delivery Across Human Skin In Vitro

Cited by 14 publications

References 52 publications

Transdermal of Atenolol via Microemulsions

Transdermal of Atenolol via Microemulsions

Effect of dosing regimen and microneedle pretreatment on in vitro skin retention of topically applied beta-blockers

Skin permeabilization for transdermal drug delivery: recent advances and future prospects

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