Surface tension and wettability in transdermal delivery: a study on the in-vitro permeation of haloperidol with cyclodextrin across human epidermis

Azarbayjani, Anahita Fathi; Lin, Hai‐Shu; Yap, Chun Wei; Chan, Yew Weng; Chan, Sui Yung

doi:10.1211/jpp.62.06.0014

Cited by 37 publications

(16 citation statements)

References 49 publications

(67 reference statements)

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“…8,9) In the present study, the effect of esters on artificial membrane permeation were evaluated and the obtained relationships between physical properties and the amount of compounds that permeated were almost similar to previous results that evaluated rat, [15][16][17] porcine, 19,20) and human 18) skins. Thus, although future research on the correlation between the permeability of artificial membrane and porcine or human skin from esters will be needed, silicone and Strat-M ® membranes might be useful in the development of pharmaceutical and cosmeceutical products.…”

Section: Discussionsupporting

confidence: 87%

Effect of Esters on the Permeation of Chemicals with Different Polarities through Synthetic Artificial Membranes Using a High-Throughput Diffusion Cell Array

et al. 2016

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) was measured and correlated with the physicochemical properties of the esters, including their solubility, viscosity, wettability, surface tension, and uptake. The amount of each model compound that permeated through the silicone membrane was not significantly correlated with the solubility of the esters but was significantly correlated with all other measured physical properties of the esters. Similar correlations were observed for the amounts of AMP, BA, and FP that passed through the Strat-M ® membrane. However, the amount of CF that permeated through the Strat-M ® membrane also correlated with the solubility of the esters. There was a highly significant correlation between the amount permeating through the silicone and Strat-M ® membranes because the model compounds had high lipophilicity. These findings demonstrated that to control the permeation of various chemicals through artificial membranes, it is important to consider the uptake of the esters and that the solubility of the esters is also an important consideration when using a more complex membrane.Key words alternative membrane; high-throughput; ester; silicone membrane; Strat-M; physical property In order to develop transdermal drug delivery systems, permeability has been evaluated using Fick's law of diffusion. 1,2)Fick's First Law indicates that the rate of mass transfer across a membrane is proportional to the concentration gradient expressed across the membrane. Synthetic artificial membranes are uniform and are designed to mimic human skin to avoid variability among tissues. They offer a simple and reproducible alternative to human and animal skins and provide key information to help understand the mechanisms of drug permeation by the evaluation of changes in a basic permeation parameter because, theoretically, skin permeation of chemicals can be expressed by physicochemical phenomena of diffusion and partition of compounds. Therefore, synthetic artificial membranes have been used in permeability evaluations. [3][4][5] Maitani et al.6) evaluated the permeability of diclofenac salts and free diclofenac acid through a silicone membrane to understand the mechanism of percutaneous absorption of ionizable drugs, and the existence of the lipid pathway for diclofenac salts was the same as for diclofenac acid. Strat-M ® is a commercially available multi-layered artificial membrane that is made from polyether sulfonic acid. 7) We reported previously also that the permeability coefficients, partition parameters, and diffusion parameters of chemicals through a Strat-M ® membrane were similar to those in human skin, and those in silicone membrane were under-or over-estimation to those in human skin, depending on the lipophilicity of the model compounds. 8,9) In addition, several previous studies have assessed the effects of vehicles on the permeation of chemicals through artificial membranes.10-13) For example, Twist and Zatz 10)evaluated the effect of alcohol on the permeation rate (flux) of methyl-, ethyl-, propyl-, and butyl-parabens. Dias et al. 12)r...

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Section: Discussionsupporting

confidence: 87%

Effect of Esters on the Permeation of Chemicals with Different Polarities through Synthetic Artificial Membranes Using a High-Throughput Diffusion Cell Array

et al. 2016

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“…Haloperidol binds hERG channels more potently than other cardiac potassium channels, whereas terfenadine also has the potential to block other ion channels [33]. Quantitative comparison of the ECG waveform before and during terfenadine treatment revealed an increase in the QTc interval in a concentration-dependent manner (n = 8 per concentration, P <0.05; Fig.…”

Section: Resultsmentioning

confidence: 91%

“…Haloperidol (a butyrophenone anti-psychotic [32]), terfenadine (a histamine H1 receptor antagonist [33]) and tubocurarine (a skeletal muscle relaxing alkaloid [34]) were obtained from Sigma Aldrich. All drug stocks were made using either DMSO or distilled water depending on solubility, then diluted using E3 embryo medium to make up the final concentrations for recording purposes with DMSO levels at 1%.…”

Section: Methodsmentioning

confidence: 99%

Optimisation of Embryonic and Larval ECG Measurement in Zebrafish for Quantifying the Effect of QT Prolonging Drugs

Dhillon

Doro

Magyary³

et al. 2013

PLoS ONE

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Effective chemical compound toxicity screening is of paramount importance for safe cardiac drug development. Using mammals in preliminary screening for detection of cardiac dysfunction by electrocardiography (ECG) is costly and requires a large number of animals. Alternatively, zebrafish embryos can be used as the ECG waveform is similar to mammals, a minimal amount of chemical is necessary for drug testing, while embryos are abundant, inexpensive and represent replacement in animal research with reduced bioethical concerns. We demonstrate here the utility of pre-feeding stage zebrafish larvae in detection of cardiac dysfunction by electrocardiography. We have optimised an ECG recording system by addressing key parameters such as the form of immobilization, recording temperature, electrode positioning and developmental age. Furthermore, analysis of 3 days post fertilization (dpf) zebrafish embryos treated with known QT prolonging drugs such as terfenadine, verapamil and haloperidol led to reproducible detection of QT prolongation as previously shown for adult zebrafish. In addition, calculation of Z-factor scores revealed that the assay was sensitive and specific enough to detect large drug-induced changes in QTc intervals. Thus, the ECG recording system is a useful drug-screening tool to detect alteration to cardiac cycle components and secondary effects such as heart block and arrhythmias in zebrafish larvae before free feeding stage, and thus provides a suitable replacement for mammalian experimentation.

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“…However, the values obtained for the same complex may vary depending on the Table 1. Chemical structure and physical properties of natural cyclodextrins and some of their derivatives found in drug delivery systems [88,94].…”

Section: Inclusion Complex Formation and Self-aggregatesmentioning

confidence: 99%

Cyclodextrin‐Based Formulations: A Non‐Invasive Platform for Targeted Drug Delivery

Muankaew

Loftsson

2017

Basic Clin Pharma Tox

159

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Cyclodextrins (CDs) are recognized as promising pharmaceutical excipients due to their unique ability to form watersoluble inclusion complexes with various poorly soluble compounds. The numerous investigations on CDs and their use in nanomedicine have received considerable attention in the last three decades, leading to the rapid development of new CD-containing formulations that significantly facilitate targeted drug delivery and controlled drug release, with consequent improvements in drug bioavailability. This MiniReview highlights the efficacy and recent uses of CDs for non-invasive drug delivery. Using ophthalmic and nasal drug delivery as examples, an overview of chemical properties, mechanisms of CDs on drug solubilization, stabilization and permeation, along with their toxicological profiles relevant to nasal and ocular administration, are provided and discussed. The recent development and application of CD-based nanocarrier systems for targeted drug delivery are summarized.Cyclodextrins (CDs) are natural cyclic oligosaccharides that are produced by enzymatic degradation of starch. There are three native CDs designated aCD, bCD and cCD, which are composed of 6, 7 and 8 D-glucopyranose units linked by a-(1, 4) glycosidic, respectively [1]. The molecules are commonly described as truncated cone, bucket-like or donut-shaped, with a hydrophilic outer surface and a relatively hydrophobic inner cavity that allows entrapment of small hydrophobic drug molecules or hydrophobic moieties of larger molecules [2], thereby providing drugs with new physicochemical characteristics without altering their intrinsic properties. Table 1 summarizes the characteristics of different CDs. Natural CDs are preferred for complexation; however, their usability is limited by the small cavity size of aCD, poor aqueous solubility of bCD and low productivity of cCD [3]. Derivatized CDs can be obtained by substituting their hydroxyl groups with desired functional moieties. Methyl-(MebCD and MecCD) [4,5], hydroxypropyl-(HPaCD, HPbCD and HPcCD) [6][7][8] and sulphobutylether (SEBbCD) derivatives [9] are frequently found in pharmaceutical products and have improved solubility and inclusion capacity over natural CDs. Pharmaceutical applications of both natural CDs and their derivatives are common when drug/CD complexes are used to increase drug solubility, improve organoleptic properties [10], enhance drug permeation [11] and increase drug stability, resulting in increased product shelf-life and drug bioavailability [12]. In addition, spontaneous self-assembly of drug/CD complexes into aggregates can lead to innovative drug delivery systems, such as CD-containing liposomes and microspheres as well as microand nanoparticles [13]. Polymerized CDs (e.g. Epi-aCD and Epi-bCD) have also been synthesized to enhance the selfassembly ability of CDs, and to strengthen their interactions with drugs and biological membranes [14]. Compared with other pharmaceutical excipients, CDs have been shown to reduce the toxicity of several drugs and are...

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Surface tension and wettability in transdermal delivery: a study on the in-vitro permeation of haloperidol with cyclodextrin across human epidermis

Abstract: It is concluded that transdermal flux of a drug through the skin may be optimised by controlling surface tension, drug solubility and skin wettability.

Cited by 37 publications

References 49 publications

Effect of Esters on the Permeation of Chemicals with Different Polarities through Synthetic Artificial Membranes Using a High-Throughput Diffusion Cell Array

Effect of Esters on the Permeation of Chemicals with Different Polarities through Synthetic Artificial Membranes Using a High-Throughput Diffusion Cell Array

Optimisation of Embryonic and Larval ECG Measurement in Zebrafish for Quantifying the Effect of QT Prolonging Drugs

Cyclodextrin‐Based Formulations: A Non‐Invasive Platform for Targeted Drug Delivery

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