Journal of pharmaceutical sciences最新文献_第5页

Enhancing transdermal drug delivery with dissolving microneedles: A review of optimization strategies and challenges 溶解微针增强经皮给药：优化策略和挑战综述。

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2026-02-04 DOI: 10.1016/j.xphs.2026.104189

Zixuan Zhang, Yongbing Sun, Haocheng Li, Jianfang Feng, Meng Cheng, Liangxing Tu

{"title":"Enhancing transdermal drug delivery with dissolving microneedles: A review of optimization strategies and challenges","authors":"Zixuan Zhang, Yongbing Sun, Haocheng Li, Jianfang Feng, Meng Cheng, Liangxing Tu","doi":"10.1016/j.xphs.2026.104189","DOIUrl":"10.1016/j.xphs.2026.104189","url":null,"abstract":"<div><div>Microneedles represent a novel transdermal drug delivery technology that relies on micron-sized needle structures. This approach effectively penetrates the stratum corneum to achieve localized or systemic therapeutic effects, addressing the pain associated with traditional injections and the low bioavailability issues of oral administration. It addresses the pain associated with traditional injections and the low bioavailability of oral administration. Dissolving microneedles have emerged as a research hotspot in microneedle technology due to their distinctive advantages, including dissolvability, ease of operation, and absence of sharp waste. They have garnered widespread attention and application in the pharmaceutical field as an efficient means to enhance transdermal drug absorption. However, many drugs (particularly poorly soluble ones) require higher transdermal absorption enhancement factors, which traditional dissolving microneedles struggle to meet. In light of this, this paper will compare dissolving microneedles with other types of microneedles, propose optimization strategies for dissolving microneedle technology, discuss existing challenges, and outline future research directions, aiming to provide valuable references for the further development of dissolving microneedles.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 7","pages":"Article 104189"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanistic dermal patch modelling for fentanyl: Linking in vitro release and permeation data to a physiologically based pharmacokinetic approach 芬太尼的机械皮肤贴片模型：将体外释放和渗透数据与基于生理的药代动力学方法联系起来。

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2026-02-23 DOI: 10.1016/j.xphs.2026.104217

Daniel Paterson, Yanling Zhang, Sebastian Polak, James F. Clarke

{"title":"Mechanistic dermal patch modelling for fentanyl: Linking in vitro release and permeation data to a physiologically based pharmacokinetic approach","authors":"Daniel Paterson, Yanling Zhang, Sebastian Polak, James F. Clarke","doi":"10.1016/j.xphs.2026.104217","DOIUrl":"10.1016/j.xphs.2026.104217","url":null,"abstract":"<div><div>Dermal physiologically based pharmacokinetic (PBPK) models can be informed by various types of data. <em>In vitro</em> permeation testing (IVPT) experiments aid parameterisation of skin permeation independent of the complexities of systemic uptake. <em>In vitro</em> release testing (IVRT) studies isolate the formulation parameters by utilising a synthetic membrane. Leveraging this data in dermal PBPK model development, via an IVRT - IVPT - <em>in vivo</em> (IVIVIV) workflow, can reduce identifiability issues arising from concurrent parameterisation of formulation and skin permeation, or fitting directly to clinical data. In this work, three fentanyl matrix patch formulations were modelled with this approach using the Simcyp MPML MechDermA simulator. Mechanistic patch models were developed for each of the three different formulations, using IVRT data to parameterise formulation differences. These formulation models were coupled to a fentanyl skin absorption model in Simcyp’s IVPT Module to simulate IVPT data. The resulting model each formulation was used to extrapolate and predict <em>in vivo</em> application, with validation against clinical data. A virtual bioequivalence study was conducted to investigate bioequivalence given differing geometries and characteristics. A validated fentanyl patch model was used to predicted plasma profiles for patches that suffered manufacturing defects, as a risk assessment exemplifying PBPK model utilisation.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 7","pages":"Article 104217"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147307052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Richard H. Guy—He has skin in the game 理查德·h·盖伊——他有自己的利益。

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2025-12-12 DOI: 10.1016/j.xphs.2025.104130

Russell O. Potts

引用次数: 0

Role of saturation dynamics in driving skin permeation from topical gel formulations 饱和动力学在驱动皮肤渗透的作用，从局部凝胶配方。

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2026-06-03 DOI: 10.1016/j.xphs.2026.104349

Srinath Rangappa, Srinivasa Ajjarapu, Vijay Kumar Shankar, Bharathi Avula, Anandavalli Varadarajan, Santanu Kundu, S. Narasimha Murthy

{"title":"Role of saturation dynamics in driving skin permeation from topical gel formulations","authors":"Srinath Rangappa, Srinivasa Ajjarapu, Vijay Kumar Shankar, Bharathi Avula, Anandavalli Varadarajan, Santanu Kundu, S. Narasimha Murthy","doi":"10.1016/j.xphs.2026.104349","DOIUrl":"10.1016/j.xphs.2026.104349","url":null,"abstract":"<div><div>The thermodynamic activity of an active pharmaceutical ingredient (API) is a key driver of permeation performance in topical formulations. This study investigated how solvent composition and evaporation impact the degree of saturation (DS) and skin permeation of three representative APIs: diclofenac sodium, metronidazole, and lidocaine. Model hydroxyethyl cellulose gels containing 1%, 10%, or 20% w/w Polyethylene Glycol (PEG-200) were prepared and characterized for solubility, pH, viscosity, and drying behavior. The solubility of all APIs increased with increasing PEG-200 concentration, whereas the DS varied correspondingly at a given drug load. Polystyrene substrate drying studies demonstrated that higher PEG-200 levels slowed solvent loss. The <em>in situ</em> drying studies on human cadaver skin using Franz cells enabled dynamic tracking of PEG-200 content and API saturation. Diclofenac sodium and lidocaine gels formulated with 1% PEG-200 showed progressively increasing DS over time and correspondingly higher permeation fluxes in in vitro permeation studies. In contrast, metronidazole gels showed little discrimination in DS and flux across PEG-200 concentrations, consistent with their hydrophilic nature and distinct solubility dynamics. The cumulative absorption confirmed a strong concordance between DS and permeation for diclofenac sodium and lidocaine, but not for metronidazole. Overall, the findings highlight that thermodynamic activity, modulated by solvent evaporation and shifts in solubility, governs the performance of topical formulations. These results underscore the value of monitoring DS profiles as predictive markers of drug delivery efficiency in topical product design.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 7","pages":"Article 104349"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preparation of novel in situ film-forming gel impregnated with clotrimazole-loaded liquid crystalline nanoparticles: In vitro, ex vivo, in vivo dermatopharmacokinetic and antifungal evaluation 新型氯霉唑负载液晶纳米颗粒原位成膜凝胶的制备：体外、离体、体内皮肤药代动力学和抗真菌评价

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2026-02-16 DOI: 10.1016/j.xphs.2026.104210

Radhika Sharma, Gautam Singhvi, Vikas Rana

{"title":"Preparation of novel in situ film-forming gel impregnated with clotrimazole-loaded liquid crystalline nanoparticles: In vitro, ex vivo, in vivo dermatopharmacokinetic and antifungal evaluation","authors":"Radhika Sharma, Gautam Singhvi, Vikas Rana","doi":"10.1016/j.xphs.2026.104210","DOIUrl":"10.1016/j.xphs.2026.104210","url":null,"abstract":"<div><div>In an attempt to conquer the significant concerns, <em>viz.</em> patient discomfort due to repeated application, low skin permeability, retention, and low therapeutic efficacy of conventional topical formulations (creams, ointments, etc.) for the management of fungal infection caused by <em>Candida albicans</em>, an alternative delivery system was aimed. Thus, the study was contemplated to formulate <em>in situ</em> film-forming gel impregnated with clotrimazole-loaded liquid crystalline nanoparticles (CLT-LCNP@FFG) for enhanced antifungal activity against <em>Candida albicans</em> infection. First, we optimized CLT-LCNP, which shows a nanosized particle (271.4 nm), encapsulation efficiency (90.00 %), drug loading (18.30 %), sustained drug release, and was found to be non-cytotoxic on HaCaT cell lines. CLT-LCNP@FFG formed a transparent, thin, homogeneous, and substantive film after topical application. <em>Ex vivo</em> skin permeation and skin deposition study demonstrated that CLT-LCNP@FFG showed 3-fold higher skin permeation and 207 % higher CLT deposition in skin layers than a marketed product (CLT-MKT; Canesten, 1% w/w CLT). The simulation analysis suggested CLT-LCNP@FFG maintained CLT concentration above the MIC for 3 times the days in rat skin and 5 times the days in human skin as compared to CLT-MKT, suggesting a reduction in dosing frequency. <em>In vivo</em> dermatopharmacokinetic parameters improved significantly with CLT-LCNP@FFG. The enhanced therapeutic efficacy of CLT-LCNP@FFG was confirmed by <em>in vitro</em> and <em>in vivo</em> antifungal activity experiments. These results showed that this hybrid system could potentially improve the efficacy of antifungal agents and patient compliance in the treatment of fungal infections.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 7","pages":"Article 104210"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and characterization of low molecular weight heparin-triethanolamine cream: Skin permeability and antithrombotic efficacy 低分子量肝素-三乙醇胺乳膏的开发和表征：皮肤渗透性和抗血栓疗效。

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2025-11-21 DOI: 10.1016/j.xphs.2025.104078

Masayori Hagimori, Seitaro Kamiya

{"title":"Development and characterization of low molecular weight heparin-triethanolamine cream: Skin permeability and antithrombotic efficacy","authors":"Masayori Hagimori, Seitaro Kamiya","doi":"10.1016/j.xphs.2025.104078","DOIUrl":"10.1016/j.xphs.2025.104078","url":null,"abstract":"<div><div>Heparin’s coagulation factor inhibitory activity varies depending on its molecular size. Low-molecular-weight heparin (LMWH), which has fewer side effects, such as bleeding, compared to unfractionated heparin, has attracted attention. To develop a LMWH formulation with high skin permeability, a LMWH-TEA (LMWH-triethanolamine) cream formulation with improved liposolubility was developed by replacing the metal ion complex of LMWH into its TEA complex. A method for quantifying LMWH-TEA was established using high-performance liquid chromatography with fluorescence detection. The partition coefficient of LMWH-TEA increased with decreasing pH, indicating enhanced lipophilicity under acidic conditions. In the skin permeation study, LMWH-TEA showed higher skin permeability than LMWH<img>Na for up to 48 h. In the carrageenan-induced rat tail thrombosis model, the group treated with 0.5 g of LMWH-TEA 0.3 % cream exhibited substantially greater antithrombotic efficacy compared to both the untreated control group and the group treated with LMWH<img>Na 0.3 % cream. LMWH-TEA can serve as a novel transdermal formulation of LMWH and may be widely adopted in clinical practice.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 7","pages":"Article 104078"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced terbinafine topical delivery to the nail by new formulation–microporation approaches 通过新配方微孔方法增强特比萘芬局部递送到指甲。

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2025-09-16 DOI: 10.1016/j.xphs.2025.103992

Camila de Almeida Perez Pimenta, Juliana Kishishita, Yohana Souza Silva, Ana Amélia Moreira Lira, M.Begoña Delgado-Charro, Leila Bastos Leal

{"title":"Enhanced terbinafine topical delivery to the nail by new formulation–microporation approaches","authors":"Camila de Almeida Perez Pimenta, Juliana Kishishita, Yohana Souza Silva, Ana Amélia Moreira Lira, M.Begoña Delgado-Charro, Leila Bastos Leal","doi":"10.1016/j.xphs.2025.103992","DOIUrl":"10.1016/j.xphs.2025.103992","url":null,"abstract":"<div><div>Effective topical antifungal nail delivery is challenged by the actives’ poor permeation across the nail plate, a thick, hard keratin, structure. This work investigated whether terbinafine ungual delivery could be improved by combining physical enhancement approaches, nail microporation and microchanneling, with new terbinafine vehicles. The new microemulsion-, liquid crystal- and thermogel- based formulations contained 2–7 % of the active, enabling higher active loads than current commercial 1 % topical products. In vitro release and permeation studies were performed using artificial membranes and healthy human nails, respectively. In vitro permeation studies demonstrated that microporation and nail microchanneling resulted in greater drug uptake into the nail and delivery to the receptor, despite the application of smaller doses of drug throughout the study. Best results were obtained with microemulsions, particularly ME5, containing 7 % of the drug. Additionally, microbiological tests performed to evaluate the antifungal activity of the formulations against <em>T. rubrum</em> and <em>C. parapsilosis</em> confirmed the superiority of the ME5 7 %. On the whole, the results reported here support the development of new nail drug delivery systems combined with physical permeation enhancers.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 7","pages":"Article 103992"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual-layer tissue scaffolds with antibacterial and regenerative properties: Integration of melt electrowriting and electrospray technologies 具有抗菌和再生特性的双层组织支架：熔体电解和电喷涂技术的集成。

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2026-03-19 DOI: 10.1016/j.xphs.2026.104249

Irem Aydos, Sabereh Nouri, Sibel Daglilar, Sena Su Torun, Sevval Gunes, Elif Ilhan, Eray Altan, Oguzhan Gunduz

{"title":"Dual-layer tissue scaffolds with antibacterial and regenerative properties: Integration of melt electrowriting and electrospray technologies","authors":"Irem Aydos, Sabereh Nouri, Sibel Daglilar, Sena Su Torun, Sevval Gunes, Elif Ilhan, Eray Altan, Oguzhan Gunduz","doi":"10.1016/j.xphs.2026.104249","DOIUrl":"10.1016/j.xphs.2026.104249","url":null,"abstract":"<div><div>Efficient wound healing requires the design of advanced biomaterials that combine structural integrity, antimicrobial functionality, and the ability to promote tissue regeneration. The paper discusses the development of dual-layer tissue scaffolds (DLS) using poly (lactic acid) (PLA) and amoxicillin (AMOX) nanoparticles at different concentrations (0.5% w/v and 1% w/v). The scaffolds were characterized using Scanning Electron Microscopy (SEM) for morphological analysis, Fourier-transform infrared spectroscopy (FTIR) for chemical interactions, Differential Scanning Calorimetry (DSC) for thermal stability, and tensile testing for mechanical properties. Swelling, degradation, drug release and drug release kinetic analyses were performed. Antibacterial efficacy against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was performed along with cytocompatibility via MTT assays using fibroblast cells. SEM revealed microporous scaffolds with approximate pore diameters of ∼370 µm for 0.05 AMOX and ∼302 µm for 0.1 AMOX. Mechanical testing demonstrated that tensile strength and strain decrease with increasing drug loading. Antibacterial testing showed activity against S. aureus but limited efficacy against E. coli. MTT assays confirmed cytocompatibility of the scaffold, showing enhanced cell viability for the DLS-0.05 AMOX scaffold. Considering the obtained results, dual-layer tissue scaffolds with antibacterial properties present significant potential for a wide range of wound care applications.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 7","pages":"Article 104249"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Presenting the Richard H. Guy dedicated issue of JPharmSci 介绍《JPharmSci》Richard H. Guy专刊。

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2026-05-20 DOI: 10.1016/j.xphs.2026.104338

Kenneth L. Audus (Editor-in-Chief)

引用次数: 0

Dermal disposition characterization and development of a retrospective level A in vitro–in vivo relationship for topical metronidazole products 外用甲硝唑产品的皮肤倾向特征和回顾性a级体内外关系的发展。

IF 3.9 3区医学

Journal of pharmaceutical sciences Pub Date : 2026-07-01 Epub Date: 2025-12-24 DOI: 10.1016/j.xphs.2025.104139

Benjamin A. Kuzma, Sharareh Senemar, Tannaz Ramezanli, Priyanka Ghosh, Sam G. Raney, Grazia Stagni

{"title":"Dermal disposition characterization and development of a retrospective level A in vitro–in vivo relationship for topical metronidazole products","authors":"Benjamin A. Kuzma, Sharareh Senemar, Tannaz Ramezanli, Priyanka Ghosh, Sam G. Raney, Grazia Stagni","doi":"10.1016/j.xphs.2025.104139","DOIUrl":"10.1016/j.xphs.2025.104139","url":null,"abstract":"<div><div>Dermal microdialysis involves the insertion of a probe into the dermis beneath an application site for a topical drug product (TDP). The probe measures local, unbound, active pharmaceutical ingredient (API or drug) concentrations in the dermis. The resulting dermal concentration-time profile is a combination of the simultaneous drug absorption and disposition (by distribution/elimination into surrounding tissues and into the dermal vasculature). For orally or subcutaneously administered drug products, the absorption process is estimated through deconvolution of plasma concentrations utilizing the unit impulse response (UIR) obtained from an intravenous administration. In this study, we implemented a retrodialysis/microdialysis (termed “dermal infusion”) approach to deliver metronidazole (MTZ) directly into the dermis allowing measurement of dermal disposition parameters (dermal clearance and dermal volume of distribution) and thus the calculation of MTZ’s dermal UIR (dUIR); The dUIR allowed for the estimation of the absorption process or <em>in vivo</em> dermal flux (input-rate) and cumulative amount (CA) permeated from MTZ TDP application. The <em>in vivo</em> (Yucatan mini-pig) CA permeated were compared with <em>in vitro</em> permeation testing data (human) to build a retrospective <em>in vitro</em> - <em>in vivo</em> relationship (IVIVR). The internal validation for C<sub>max</sub> and AUC<sub>0–48hr</sub> prediction errors indicated a reliable IVIVR. These results suggest that the dermal infusion approach can be used to study dermal API disposition, which can aid in the comprehension of <em>in vivo</em> cutaneous pharmacokinetic (cPK) data. Furthermore, a mechanistic cPK understanding is essential for the successful development of new topical therapeutics and assessment of bioequivalence of TDPs, alike.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"115 7","pages":"Article 104139"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0