Pharmacokinetic Evaluation of a Novel Donepezil-Loaded Dissolving Microneedle Patch in Rats

Research on the development of dissolving microneedles (DMNs) has focused on bolus drug delivery, with little attention on sustained release. Here, we evaluated the sustained release, absorption pattern, and effective drug permeation of a novel donepezil-loaded DMN patch through an in vivo investigation on rats. The applications of DMN patches to the shaved skin of rats for 1 week and 1 h were compared with oral donepezil administration to assess their sustained release capabilities. We used a validated liquid chromatography–tandem mass spectrometry method to quantify donepezil in the plasma. We found that the microneedle arrays effectively delivered donepezil across the skin, with dissolution observed within 1 h of application. Furthermore, skin irritation test showed that the patches produced no irritation response. The DMN arrays also effectively increased drug permeation and demonstrated sustained release and absorption of donepezil from DMN patches. These patches allow extended dosing intervals, reduced gastrointestinal adverse effects, and convenient self-administration to mitigate poor drug compliance, making them beneficial for the treatment of elderly patients with Alzheimer’s disease.

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Optimized Preparation of Capsaicin-Loaded Nanoparticles Gel by Box-Behnken Design

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.1061-1062.359 ◽

2014 ◽

Vol 1061-1062 ◽

pp. 359-368 ◽

Cited By ~ 1

Author(s):

Mei Ling Tang ◽

Li Hua Chen ◽

Dong Sheng Zhou ◽

Wei Feng Zhu ◽

Yong Mei Guan ◽

...

Keyword(s):

Skin Permeation ◽

Skin Irritation ◽

Morphological Characteristics ◽

Entrapment Efficiency ◽

Box Behnken Design ◽

Irritation Test ◽

Predicted Values ◽

Skin Irritation Test

A three-factor three-level Box-Behnken design(BBD) was employed to optimize capsaicin-loaded nanoparticles(Cap-NPs), and its properties in vitro and in vivo were evaluated. Particle size, morphological characteristics, entrapment efficiency of Cap-NPs were investigated respectively by Zetasizer, H7000 TEM and HPLC. Release, skin permeation and skin irritation test were investigated on mouse and rabbits. The predicted values of Cap-NPs were 94.50±6.33% for entrapment efficiency(EE) and 170.30±7.81 nm for particle mean diameter(PMD) under optimal conditions which were 346.33 bar (homogenization pressure, X1), 4.67 min(homogenization time, X2), and 15421.42 rpm (shear rate, X3). The in vitro permeation study showed that capsaicin permeability in NPs-gel was a 2.80-fold greater flux values than conventional ointment after 24 h. Cap-NPs-gel produce no observable skin irritation in rabbits within 72h. The optimized Cap-NPs-gel would be a good candidate for transdermal delivery.

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ChemSkin Reference Chemical Database for the Development of an In Vitro Skin Irritation Test

Toxics ◽

10.3390/toxics9110314 ◽

2021 ◽

Vol 9 (11) ◽

pp. 314

Author(s):

Juhee Han ◽

Ga-Young Lee ◽

Green Bae ◽

Mi-Jeong Kang ◽

Kyung-Min Lim

Keyword(s):

Pearson Correlation ◽

Skin Irritation ◽

Test Method ◽

Predictive Capacity ◽

Chemical Database ◽

Irritation Test ◽

Commercial Sources ◽

Skin Irritation Test

Since the animal test ban on cosmetics in the EU in 2013, alternative in vitro safety tests have been actively researched to replace in vivo animal tests. For the development and evaluation of a new test method, reference chemicals with quality in vivo data are essential to assess the predictive capacity and applicability domain. Here, we compiled a reference chemical database (ChemSkin DB) for the development and evaluation of new in vitro skin irritation tests. The first candidates were selected from 317 chemicals (source data n = 1567) searched from the literature from the last 20 years, including previous validation study reports, ECETOC, and published papers. Chemicals showing inconsistent classification or those that were commercially unavailable, difficult or dangerous to handle, prohibitively expensive, or without quality in vivo or in vitro data were removed, leaving a total of 100 chemicals. Supporting references, in vivo Draize scores, UN GHS/EU CLP classifications and commercial sources were compiled. Test results produced by the approved methods of OECD Test No. 439 were included and compared using the classification table, scatter plot, and Pearson correlation analysis to identify the false predictions and differences between in vitro skin irritation tests. These results may provide an insight into the future development of new in vitro skin irritation tests.

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Acute irritation of tetracyclic c-4-hydroxyphenylcalics [4] pyrogalolarene on skin of albino rabbits

Indonesian Journal of Pharmacology and Therapy ◽

10.22146/ijpther.480 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Aditya Nugraha ◽

Dwi Aris Agung Nugrahaningsih ◽

Rul Afiyah Syarif ◽

Mia Munawaroh Yuniyanti ◽

Ikhsan Nur Salim ◽

...

Keyword(s):

Antioxidant Activity ◽

Chemical Compound ◽

Skin Irritation ◽

Control Site ◽

International Organization ◽

Irritation Test ◽

Skin Irritation Test ◽

Primary Irritation ◽

Primary Irritation Index

C-4-hydroxyphenylcalix[4] pyrogalolarene (Pg4OH) is a synthetic chemical compound that shows strong antioxidant activity. It is potential to be developed as UV skin protector. For topical admission, an acute skin irritation test is being prerequisite to be fulfill. This study was conducted to investigate the irritation effect of Pg4OH on the skin. In vivo study by quasi experiment with posttest only design was carried out by employing 3 adult male albino rabbits. The back hair was shaved at 24 h before the treatment. The Pg4OH was smeared on the bare shaved-skin and left naturally within 4 h. The observation began at 24, 48 and 72 h after exposure. The erythema and edema scores were measured. Calculation by using primary irritation index (PII) was applied. Calculation was categorized with globally harmonized system (GHS) and international organization for standardization (ISO) parameters. As a result, among three rabbits, only one animal shown erythema and edema with very small size (score: 1), on 3 sites, at 72 h. Both the control site and the sample sites gained same score. Two other rabbits were obtained 0 value at each observation location. According to the PII, the observed data was obtained score 0.0093 (very light or negligible). It can be concluded that the tetracyclic compound of Pg4OH does not irritate the skin.

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International validation of an in vitro skin irritation test protocol (EpiDerm-SIT) to replace the in vivo rabbit test for hazard identification of chemicals

Toxicology Letters ◽

10.1016/j.toxlet.2009.06.249 ◽

2009 ◽

Vol 189 ◽

pp. S83 ◽

Cited By ~ 1

Author(s):

Manfred Liebsch ◽

Armin Gamer ◽

Rodger Curren ◽

Jürgen Frank ◽

Elke Genschow ◽

...

Keyword(s):

Skin Irritation ◽

Hazard Identification ◽

Test Protocol ◽

Irritation Test ◽

Skin Irritation Test

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Review of skin irritation/corrosion hazards on the basis of human data: a regulatory perspective

Interdisciplinary Toxicology ◽

10.2478/v10102-012-0017-2 ◽

2012 ◽

Vol 5 (2) ◽

pp. 98-104 ◽

Cited By ~ 26

Author(s):

David Basketter ◽

Dagmar Jírova ◽

Helena Kandárová

Keyword(s):

Patch Test ◽

Skin Irritation ◽

Alternative Methods ◽

Test Protocol ◽

Rabbit Skin ◽

Irritation Test ◽

Skin Irritation Test

Abstract Regulatory classification of skin irritation has historically been based on rabbit data, however current toxicology processes are transitioning to in vitro alternatives. The in vitro assays have to provide sufficient level of sensitivity as well as specificity to be accepted as replacement methods for the existing in vivo assays. This is usually achieved by comparing the in vitro results to classifications obtained in animals. Significant drawback of this approach is that neither in vivo nor in vitro methods are calibrated against human hazard data and results obtained in these assays may not correspond to situation in human. The main objective of this review was to establish an extended database of substances classified according to their human hazard to serve for further development of alternative methods relevant to human health as well as resource for improved regulatory classification. The literature has been reviewed to assemble all the available information on the testing of substances in the human 4 h human patch test, which is the only standardized protocol in humans matching the exposure conditions of the regulatory accepted in vivo rabbit skin irritation test. A total of 81 substances tested according to the defined 4 h human patch test protocol were found and collated into a dataset together with their existing in vivo classifications published in the literature. While about 50% of the substances in the database are classified as irritating based on the rabbit skin test, on using the 4 h HPT test, less than 20% were identified as acutely irritant to human skin. Based on the presented data, it can be concluded that the rabbit skin irritation test largely over-predicts human responses for the evaluated chemicals. Correct classification of the acute skin irritation hazard will only be possible if newly developed in vitro toxicology methods will be calibrated to produce results relevant to man.

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