Formulation development and evaluation, in silico PBPK modeling and in vivo pharmacodynamic studies of clozapine matrix type transdermal patches

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 7, 2025

Clozapine is a potent serotonin receptor antagonist and commonly used for the treatment of Schizophrenia. The study aimed to develop optimize transdermal matrix patch clozapine. A 3-level, 3-factor Central Composite Design was applied examine validate impact various formulation variables, Eudragit, PEG, oleic acid on in vitro drug release, flux, tensile strength (TS). Different characteristics were studied terms physico-chemical characterization, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), release performance, permeability. numerical graphical optimization based desirability function optimized obtained from polynomial equation further validated evaluated targeted critical attributes. skin irritation, vivo pharmacodynamics, silico prediction, simulation using GastroPlus TCAT® model stability. experimental results formulation, such as 1.220 kg/cm2, flux 147.376 μg/cm2/h Q24 94.874%, showed similarity with values predicted by optimization. In Neuro-pharmacological studies that comparable standard. Cmax, Tmax, AUCt, AUCinf 38.396 ng/mL, 28.960 h, 1625.500 ng-h/mL, 1175.700 ng-h/mL 50 mg patch. No irritation found per Draize score method. shelf life 30.41 months under accelerated conditions. matrix-type clozapine can be management schizophrenia improved patient compliance.

Language: Английский

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Fabrication and Evaluation of Dissolving Hyaluronic Acid Microneedle Patches for Minimally Invasive Transdermal Drug Delivery by Nanoimprinting

Gels, Journal Year: 2025, Volume and Issue: 11(2), P. 89 - 89

Published: Jan. 23, 2025

Transdermal drug delivery minimizes pain and provides a controlled, stable release of drugs, but its effectiveness is limited by the skin’s natural barriers. Microneedles overcome this problem, enabling minimally invasive delivery. Microneedle patches (MNPs) with 80 µm-tall needles composed hyaluronic acid (HA) were developed evaluated for their formability, structural integrity, dissolution rate, skin penetration ability, transmission capacity. The influence molecular weight HA on these properties was also investigated. MNPs made from low-molecular-weight (30 kDa–50 kDa) demonstrated 12.5 times superior permeability in ex vivo human compared to needleless (NLPs). Furthermore, same test, had 1.7 higher than high-molecular-weight MNPs, suggesting transdermal administration. significantly influenced solubility permeability, highlighting potential as systems. Puncture tests depth 50–60 µm, indicating minimal nerve irritation dermis effective superficial dermal layer. These results present manufacturing technique incorporating model compounds highlight novel method biomedical applications soft gels.

Language: Английский

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Microneedles Based on a Biodegradable Polymer—Hyaluronic Acid

Polymers, Journal Year: 2024, Volume and Issue: 16(10), P. 1396 - 1396

Published: May 14, 2024

Transdermal transport can be challenging due to the difficulty in diffusing active substances through outermost layer of epidermis, as primary function skin is protect against entry exogenous compounds into body. In addition, penetration epidermis for hydrophilic nature and particles larger than 500 Da highly limited physiological properties non-polar its layer, namely stratum corneum. A solution this problem use microneedles, which “bypass” problematic epidermal by dispensing substance directly deeper layers skin. Microneedles obtained with various materials come different types. Of special interest are carriers based on biodegradable biocompatible polymers, such polysaccharides. Therefore, paper reviews latest literature methods obtain hyaluronic acid-based microneedles. It focuses current advancements field consequently provides an opportunity guide future research area.

Language: Английский

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Potentials of ionic liquids to overcome physical and biological barriers

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 204, P. 115157 - 115157

Published: Dec. 15, 2023

Language: Английский

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Progress in Topical and Transdermal Drug Delivery Research—Focus on Nanoformulations

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(6), P. 817 - 817

Published: June 16, 2024

Skin is the largest organ and a multifunctional interface between body its environment. It acts as barrier against cold, heat, injuries, infections, chemicals, radiations or other exogeneous factors, it also known mirror of soul. The skin involved in temperature regulation by storage fat water. an interesting tissue regard to local transdermal application active ingredients for prevention treatment pathological conditions. Topical delivery emerging route drug cosmetic administration. beneficial avoiding side effects rapid metabolism. Many pharmaceutical, technological innovations have been described patented recently field. In this review, main features morphology physiology are presented being followed description classical novel nanoparticulate dermal formulations. biophysical aspects penetration drugs cosmetics into across their investigation diffusion chambers, skin-on-a-chip devices, high-throughput measuring systems with advanced analytical techniques shown. current knowledge about mathematical modeling future perspectives briefly discussed end, all involving nanoparticulated systems.

Language: Английский

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Optical Methods for Non-Invasive Determination of Skin Penetration: Current Trends, Advances, Possibilities, Prospects, and Translation into In Vivo Human Studies

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(9), P. 2272 - 2272

Published: Sept. 3, 2023

Information on the penetration depth, pathways, metabolization, storage of vehicles, active pharmaceutical ingredients (APIs), and functional cosmetic (FCIs) topically applied formulations or contaminants (substances) in skin is great importance for understanding their interaction with targets, treatment efficacy, risk assessment—a challenging task dermatology, cosmetology, pharmacy. Non-invasive methods qualitative quantitative visualization substances vivo are favored limited to optical imaging spectroscopic such as fluorescence/reflectance confocal laser scanning microscopy (CLSM); two-photon tomography (2PT) combined autofluorescence (2PT-AF), fluorescence lifetime (2PT-FLIM), second-harmonic generation (SHG), coherent anti-Stokes Raman scattering (CARS), reflectance (2PT-RCM); three-photon (3PT); micro-spectroscopy (CRM); surface-enhanced (SERS) micro-spectroscopy; stimulated (SRS) microscopy; coherence (OCT). This review summarizes state art use CLSM, 2PT, 3PT, CRM, SERS, SRS, OCT study non-invasively (302 references). The advantages, limitations, possibilities, prospects reviewed comprehensively discussed. ex studies discussed potentially translatable into measurements. requirements properties determine by certain highlighted.

Language: Английский

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Medicinal Anti-Inflammatory Patch Loaded with Lavender Essential Oil

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6171 - 6171

Published: June 4, 2024

Transdermal drug delivery offers a promising alternative for administering medications like ibuprofen, known its analgesic and anti-inflammatory properties, with reduced gastrointestinal side effects compared to oral administration. This study explored the potential synergistic of combining ibuprofen lavender essential oil (LEO) in transdermal patches. The composition LEO was analyzed, revealing predominant compounds such as linalyl acetate linalool, which are their properties. physicochemical properties patches were investigated, indicating improved cohesion addition LEO. Additionally, thermal stability assessments demonstrated enhanced incorporation an increase onset decomposition temperature from 49.0 67.9 °C. antioxidant activity containing significantly higher free radical scavenging ability 79.13% RSA 60% without Release permeation studies showed that exhibited increased through skin 74.40% released LEO-containing 36.29% after 24 h. Moreover, rate notably faster LEO, quicker therapeutic effects. inclusion holds promise enhancing efficiency effectiveness, offering strategy pain management

Language: Английский

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Skin Structure, Physiology, and Pathology in Topical and Transdermal Drug Delivery

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(11), P. 1403 - 1403

Published: Oct. 31, 2024

Several industries are increasingly focused on enhancing the delivery of active ingredients through skin to optimize therapeutic outcomes. By facilitating penetration barrier, these enhancers can significantly improve efficacy various formulations, ranging from skincare products agents targeting systemic circulation. As understanding physiology and mechanisms drug absorption deepen, adopting permeation more widely, ultimately leading better patient outcomes expanded treatment options. However, structure physiological function vary according different factors, such as area body between individuals. These variations, along with external environmental exposures, aging pathological conditions, introduce complexities that must be carefully considered when designing effective systems. Considering intricacies physiology, tailoring systems account for regional differences, individual variability, changes induced by factors or disease is critical optimizing This review discusses features structure, pathologies, well application in contexts. Furthermore, it addresses use animal models transdermal dermatological studies, latest developments this field.

Language: Английский

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A Comprehensive Review on Potential Chemical and Herbal Permeation Enhancers Used in Transdermal Drug Delivery Systems

Recent Advances in Drug Delivery and Formulation, Journal Year: 2024, Volume and Issue: 18(1), P. 21 - 34

Published: Jan. 23, 2024

Using skin patches to deliver drugs is dependable and doesn't have the same issues as permeation enhancers, which help get through but struggle because of skin's natural barrier. Strategies are required increase topical bioavailability enhance drug absorption. Natural compounds offer a promising solution by temporarily reducing barrier resistance improving substances allow wider variety medications be distributed stratum corneum, offering approach enhancing transdermal delivery. distinct advantages permeability enhancers. They pharmacologically effective safe, inactive, non-allergenic, non-irritating. These characteristics ensure their suitability for use without causing adverse effects. readily available well tolerated body. Studies investigating structure-activity relationship chemicals demonstrated significant enhancer By understanding connection between chemical composition activity, researchers can identify penetration. In conclusion, current research focuses on utilizing enhancers in therapy systems. safety, non-toxicity, pharmacological inactivity, non-irritation. Through investigations, advancements been made holds enormous potential penetration trans-dermally delivered medications.

Language: Английский

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Chiral Supramolecular Hydrogel Enhanced Transdermal Delivery of Sodium Aescinate to Modulate M1 Macrophage Polarization Against Lymphedema

Advanced Science, Journal Year: 2023, Volume and Issue: 11(5)

Published: Dec. 1, 2023

Abstract Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, is commonly administered intravenously clinical practice and often accompanied by severe toxic side effects short metabolic cycles. Herein, SA‐loaded chiral supramolecular hydrogels are prepared to prove curative SA on enhance its safety transdermal transmission efficiency. In vitro studies demonstrate that SA‐ loaded modulate local immune responses inhibiting macrophage polarization. Typically, these significantly increase permeability with good biocompatibility due high enantioselectivity between gelators stratum corneum L‐type found have preferable drug penetration over D‐type hydrogels. vivo show topical delivery via results dramatic therapeutic lymphedema. Specifically, downregulate level inflammatory cytokines, reduce development fibrosis, promote regeneration lymphatic vessels. This study initiates use treatment creation an effective biological platform improved administration.

Language: Английский

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