scholarly journals Modelling drug flux through microporated skin

2016 ◽  
Vol 241 ◽  
pp. 194-199 ◽  
Author(s):  
Alexey S. Rzhevskiy ◽  
Richard H. Guy ◽  
Yuri G. Anissimov
Keyword(s):  
Drug Flux

scholarly journals Amorphous Ropinirole-Loaded Mucoadhesive Buccal Film: A Potential Patient-Friendly Tool to Improve Drug Pharmacokinetic Profile and Effectiveness

2020 ◽  
Vol 10 (4) ◽  
pp. 242
Author(s):  
Giulia Di Prima ◽  
Giuseppina Campisi ◽  
Viviana De Caro
Keyword(s):  
Buccal Mucosa ◽  
Therapeutic Strategy ◽  
Therapeutic Response ◽  
Ex Vivo ◽  
Hepatic Metabolism ◽  
Pharmacokinetic Profile ◽  
Promising Candidate ◽  
Steady State Condition ◽  
Drug Pharmacokinetic ◽  
Drug Flux

Nowadays the therapeutic strategies to manage Parkinson’s Disease are merely symptomatic and consist of administering L-DOPA and/or dopamine receptor agonists. Among these, Ropinirole (ROP) is a widely orally-administered molecule, although it is extensively susceptible to hepatic metabolism. Since literature reports the buccal mucosa as a potentially useful route to ROP administration, the development of novel, effective, and comfortable oromucosal formulations should prove desirable in order to both enhance the therapeutic efficacy of the drug and allow a personalized therapeutic strategy able to meet the patient’s needs. The results of the proposed ROP film as a new dosage form show that it is flexible; uniform; and characterized by suitable surface pH; good mucoadhesiveness; low swelling degree; and fast, complete drug release. Moreover, after ex vivo evaluation on a film having an area of 0.282 cm2 and dose of 2.29 mg, the results of drug flux through the buccal mucosa are closely comparable to the amount of ROP that reaches the bloodstream at the steady-state condition after ROP-PR 4 mg oral administration, calculated according to the literature (0.237 mg/cm2·h−1 vs. 0.243 mg/h, respectively). Moreover, drug flux and ROP dose could be accurately modulated time-by-time depending on the patient’s need, by varying the administered disk area. In addition, the proposed ROP film displays no lag time, producing an immediate drug input in the bloodstream, which could result in a prompt therapeutic response. These findings make ROP film a potentially comfortable and patient-friendly formulation, and a promising candidate for further clinical trials.

Role of Stratum Corneum Lipid Fluidity in Transdermal Drug Flux

1987 ◽  
Vol 76 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Guia M. Golden ◽  
James E. McKie ◽  
Russell O. Potts
Keyword(s):  
Stratum Corneum ◽  
Lipid Fluidity ◽  
Stratum Corneum Lipid ◽  
Drug Flux

Drug flux across polyacrylic acid grafted polyvinylidene fluoride membrane

1996 ◽  
Vol 4 ◽  
pp. S155
Author(s):  
S. Äkeman ◽  
K. Järvinen ◽  
K. Konturri ◽  
P. Vinikka ◽  
B. Svarfvar ◽  
...  
Keyword(s):  
Polyacrylic Acid ◽  
Polyvinylidene Fluoride ◽  
Drug Flux

scholarly journals Drug Flux Across RPE Cell Models: The Hunt for An Appropriate Outer Blood–Retinal Barrier Model for Use in Early Drug Discovery

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 176 ◽  
Author(s):  
Laura Hellinen ◽  
Heidi Hongisto ◽  
Eva Ramsay ◽  
Kai Kaarniranta ◽  
Kati-Sisko Vellonen ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Retinal Pigment ◽  
Cell Monolayer ◽  
Barrier Properties ◽  
Cell Models ◽  
Blood Retinal Barrier ◽  
Rpe Cells ◽  
Cell Monolayers ◽  
Value Range ◽  
Drug Flux

The retinal pigment epithelial (RPE) cell monolayer forms the outer blood–retinal barrier and has a crucial role in ocular pharmacokinetics. Although several RPE cell models are available, there have been no systematic comparisons of their barrier properties with respect to drug permeability. We compared the barrier properties of several RPE secondary cell lines (ARPE19, ARPE19mel, and LEPI) and both primary (hfRPE) and stem-cell derived RPE (hESC-RPE) cells by investigating the permeability of nine drugs (aztreonam, ciprofloxacin, dexamethasone, fluconazole, ganciclovir, ketorolac, methotrexate, voriconazole, and quinidine) across cell monolayers. ARPE19, ARPE19mel, and hfRPE cells displayed a narrow Papp value range, with relatively high permeation rates (5.2–26 × 10−6 cm/s. In contrast, hESC-RPE and LEPI cells efficiently restricted the drug flux, and displayed even lower Papp values than those reported for bovine RPE-choroid, with the range of 0.4–32 cm−6/s (hESC-RPE cells) and 0.4–29 × 10−6 cm/s, (LEPI cells). Therefore, ARPE19, ARPE19mel, and hfRPE cells failed to form a tight barrier, whereas hESC-RPE and LEPI cells restricted the drug flux to a similar extent as bovine RPE-choroid. Therefore, LEPI and hESC-RPE cells are valuable tools in ocular drug discovery.

Evaluation of Passive and Iontophoretic Transport of Lisinopril from Hydrogel Matrix Across Model Membrane In Vitro

2010 ◽  
Vol 2 (1) ◽  
Author(s):  
Faruk A ◽  
Ishar P.S.
Keyword(s):  
Current Density ◽  
Drug Concentration ◽  
Drug Effect ◽  
Passive Diffusion ◽  
Rat Skin ◽  
Hydrogel Matrix ◽  
Drug Flux ◽  
Current Densities ◽  
Cathodal Current

Clinical studies of lisinopril delivery through iontophoresis are highly desired for better controls over transdermal drug flux. Therefore, investigations were carried out to ascertain the relative importance of the various factor for iontophoretic transport using an ionizable drug lisinopril, which has four pKa values 2.4, 4.0 (for amino group) and 6.7, 7.0 (for carboxylic group). Ionization of lisinopril varies with pH, hence rate and extent of transport across the skin can be enhanced, controlled and manipulated by the application of factors like anodal and cathodal current at varied pH of donor solution and current densities. To determine these parameters, experiments were performed and data were collected at 3.0, 4.0 and 7.4 pH using 4 mg/ml drug concentration and 0.1 mA/cm2 current density for 10 hours. After establishing the pH for optimum transport of drug, effect of current density (0.1, 0.2, 0.3 and 0.4 mA/cm2) on the transport of drug (keeping drug concentration constant) were investigated. Passive diffusion of lisinopril was maximal at pH 3.0, when unionized form of drug was 45%. Anodal iontophoresis was most effective (significant result, p less than 0.05) in transport of drug across skin as compared to cathodal iontophoresis at pH 3.0. While at pH 4.0, cathodal iontophoretic transport of lisinopril across rat skin was highly effective (Student‘t’ test, p less than 0.05) compared to anodal iontophoresis. The effect of current density on steady state flux of lisinopril during cathodal iontophoresis at 7.4 pH was 1.33 ± 1.12 and 24.8 ± 3.1 μg/cm2/h at 0.0 under passive diffusion and 4 mA/cm2, respectively. Thus, flux was enhanced nearly 18.6 times during anodal iontophoresis as compared to passive diffusion. For cathodal flux at pH 3.0 on similar iontophoretic treatment showed enhancement nearly 4 times.

scholarly journals Enhanced Topical Delivery of Tetrandrine by Ethosomes for Treatment of Arthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Chao Fan ◽  
Xinru Li ◽  
Yanxia Zhou ◽  
Yong Zhao ◽  
Shujin Ma ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Ex Vivo ◽  
Topical Delivery ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Weak Base ◽  
Rat Skin ◽  
Adjuvant Induced Arthritis ◽  
Loading Method ◽  
Drug Flux

The purpose of this work was to explore the feasibility of ethosomes for improving the antiarthritic efficacy of tetrandrine by topical application. It was found that tetrandrine was a weak base (pKa=7.06) with pH-dependent partition coefficient. The spherical-shaped ethosomes were prepared by pH gradient loading method.Ex vivopermeation and deposition behavior demonstrated that the drug flux across rat skin and deposition of the drug in rat skin for ethosomes was 2.1- and 1.7-fold higher than that of liposomes, respectively. Confocal laser scanning microscopy confirmed that ethosomes could enhance the topical delivery of the drug in terms of depth and quantity compared with liposomes. The ethosomes were shown to generate substantial enhancement of therapeutic efficacy of tetrandrine on Freund’s complete adjuvant-induced arthritis with regard to liposomes. These results indicated that ethosomes would be a promising carrier for topical delivery of tetrandrine into and across the skin.

Acylcarnitine Chain Length Influences Carnitine-enhanced Drug Flux through the Spinal Meninges

1997 ◽  
Vol 86 (3) ◽  
pp. 642-648 ◽  
Author(s):  
Wolfgang C. Ummenhofer ◽  
Christopher M. Bernards
Keyword(s):  
Chain Length ◽  
Cell Model ◽  
Acyl Chain ◽  
Epidural Administration ◽  
Hydrophilic Drugs ◽  
Palmitoyl Carnitine ◽  
Before And After ◽  
Drug Flux ◽  
Chain Lengths

Background Palmitoyl carnitine has been shown to improve the penetration of hydrophilic drugs through the spinal meninges. Naturally occurring acylcarnitines, however, exist as a homologous series of different acyl chain lengths. The purpose of this study was to determine the most effective acylcarnitine chain length to increase meningeal permeability. Methods The transmeningeal flux of mannitol, morphine, and sufentanil through monkey spinal meninges was determined before and after adding acylcarnitines with chain lengths of 6 to 18 carbon atoms. Flux was measured using a previously established in vitro diffusion cell model. Results For mannitol, acylcarnitines generally showed a greater penetration-enhancing effect with increasing chain length, with palmitoyl carnitine (16 carbons) being the most effective compound with an increase of 244 +/- 29% (means +/- SE). Morphine flux was increased most significantly by lauroyl-(12 carbons) and myristoyl-carnitine (14 carbons) with 165 +/- 25% and 188 +/- 44% flux increases, respectively. In contrast, none of the studied acylcarnitines significantly altered the meningeal penetration of the more hydrophobic drug sufentanil. Conclusions The results suggest that, to promote hydrophilic drug penetration, acylcarnitines must surpass a critical chain length (10 carbon units) but should not exceed 16 carbon units. The activity of the acylcarnitines at the spinal meninges is reduced on either side of this range. The ability of acylcarnitines to increase the transmeningeal flux of morphine in vitro suggests that lauroyl or myristoyl carnitine may increase the spinal bioavailability of morphine after epidural administration.

scholarly journals Assessment of dermal bioavailability: predicting the input function for topical glucocorticoids using stratum corneum sampling

2021 ◽  
Author(s):  
Andrea Pensado ◽  
Anita McGrogan ◽  
K. A. Jane White ◽  
Annette L. Bunge ◽  
Richard H. Guy ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Elimination Rate ◽  
Input Function ◽  
Tape Stripping ◽  
Viable Epidermis ◽  
Quantitative Metrics ◽  
Topical Glucocorticoids ◽  
Stripping Method ◽  
Drug Flux ◽  
Larger Sample

AbstractPredicting the dermal bioavailability of topically delivered drugs is challenging. In this work, minimally invasive stratum corneum (SC) sampling was used to quantify the delivery of betamethasone valerate (BMV) into the viable skin. Betnovate® cream (0.1% w/w BMV) was applied at three doses (2, 5, and 10 mg cm−2) to the ventral forearms of 12 healthy volunteers. The mass of drug in the SC was measured using a validated tape-stripping method (a) after a 4-h “uptake” period, and (b) following a 6-h “clearance” period subsequent to cream removal. Concomitantly, the skin blanching responses to the same doses were assessed with a chromameter over 22 h post-application. BMV uptake into the SC was significantly higher for the 5 mg cm−2 dose compared to those of 2 and 10 mg cm−2. In all cases, ~30% of the drug in the SC at the end of the uptake period was cleared in the subsequent 6 h. From the SC sampling data, the average drug flux into the viable epidermis and its first-order elimination rate constant from the SC were estimated as 4 ng cm−2 h−1 and 0.07 h−1, respectively. In contrast, skin blanching results were highly variable and insensitive to the dose of cream applied. The SC sampling method was able to detect a 50% difference between two applied doses with 80% power; detection of a 20% difference would require a larger sample size. SC sampling enabled quantitative metrics describing corticosteroid delivery to the viable epidermis to be determined. Graphical abstract

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