Pub Date : 2026-02-28DOI: 10.1016/j.ijpharm.2026.126721
Sina Simon, Marie-Anne Westwood, Thanusa Shanmugalingam, Carina Cantrill, Claus-Michael Lehr
The majority of anti-infectives are administered via the systemic route to patients suffering from pulmonary infections. Therefore, the aim of this study was to mechanistically investigate pulmonary disposition of drugs through evaluation of rate and extent using human lung epithelium cell and binding assays in vitro. A set of 20 marketed anti-infectives were assessed to measure binding to plasma and epithelial lining fluid (ELF), and their permeability and active efflux. To estimate the extent of drug distribution, it is of importance to measure the unbound fraction is relevant matrices. The unbound fractions of anti-infectives in plasma and ELF were measured and revealed a moderate correlation (r2 = 0.784) and further highlighted that unbound fractions in ELF are likely < 100 %. The apparent permeability (i.e. the rate of movement) was measured in bidirectional studies, where a two-/three-fold lower permeability was observed in Calu-3 and hAELVi cells when compared to routinely used models in drug discovery, LLC-PK1 and Caco-2 - notably, with a greater influence on highly permeable molecules (> 100 nm/s). Active efflux was observed in bronchial Calu-3 (likely mediated by P-glycoprotein), but not in alveolar hAELVi, suggesting potential differences in efflux transporter contributions in the upper versus lower airways in vitro. Overall, this in vitro investigation has contributed to deepen our mechanistic understanding of pharmacokinetic parameters affecting the pulmonary disposition of anti-infectives in humans and highlights opportunities to implement in translational strategies when predicting lung disposition.
{"title":"Transport of 20 marketed anti-infectives across the human lung epithelium in vitro.","authors":"Sina Simon, Marie-Anne Westwood, Thanusa Shanmugalingam, Carina Cantrill, Claus-Michael Lehr","doi":"10.1016/j.ijpharm.2026.126721","DOIUrl":"10.1016/j.ijpharm.2026.126721","url":null,"abstract":"<p><p>The majority of anti-infectives are administered via the systemic route to patients suffering from pulmonary infections. Therefore, the aim of this study was to mechanistically investigate pulmonary disposition of drugs through evaluation of rate and extent using human lung epithelium cell and binding assays in vitro. A set of 20 marketed anti-infectives were assessed to measure binding to plasma and epithelial lining fluid (ELF), and their permeability and active efflux. To estimate the extent of drug distribution, it is of importance to measure the unbound fraction is relevant matrices. The unbound fractions of anti-infectives in plasma and ELF were measured and revealed a moderate correlation (r<sup>2</sup> = 0.784) and further highlighted that unbound fractions in ELF are likely < 100 %. The apparent permeability (i.e. the rate of movement) was measured in bidirectional studies, where a two-/three-fold lower permeability was observed in Calu-3 and hAELVi cells when compared to routinely used models in drug discovery, LLC-PK1 and Caco-2 - notably, with a greater influence on highly permeable molecules (> 100 nm/s). Active efflux was observed in bronchial Calu-3 (likely mediated by P-glycoprotein), but not in alveolar hAELVi, suggesting potential differences in efflux transporter contributions in the upper versus lower airways in vitro. Overall, this in vitro investigation has contributed to deepen our mechanistic understanding of pharmacokinetic parameters affecting the pulmonary disposition of anti-infectives in humans and highlights opportunities to implement in translational strategies when predicting lung disposition.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126721"},"PeriodicalIF":5.2,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-27DOI: 10.1016/j.ijpharm.2026.126707
Di Chang, Jingrong Xu, Chenhao Yang, Yanli An, Dongfang Liu
Vascular calcification (VC), a critical pathological complication in chronic kidney disease, type 2 diabetes mellitus, and atherosclerosis, is also a major risk factor for adverse cardiovascular events. Once considered a passive age-related process, VC is now recognized as a highly dynamic and multifactorial process involving an array of biological events, including oxidative stress, cellular phenotypic differentiation, and disruptions in calcium-phosphate homeostasis, among others. To date, no specific pharmacological therapies for VC have been established. Existing drug candidates in VC clinical trials often exhibit limitations like short half-lives and poor targeting efficiency, and systemic drug administration is limited by low efficacy and a high risk of adverse effects, which hinders clinical translation. In recent years, nanomaterials have emerged as promising therapeutic strategies to mitigate the dynamic pathological process of VC by virtue of microenvironment-responsive release, multi-target synergistic regulation, and precise enrichment at lesion sites, with the potential to overcome barriers to clinical translation. This review consolidates the pathophysiological mechanisms of VC, systematically evaluates recent advances in nanomaterial-based VC therapies, and analyzes future research directions based on existing evidence, with the goal of providing a theoretical foundation and innovative strategies to overcome current clinical barriers in VC management.
{"title":"Engineered nanomaterials for targeted therapy of vascular calcification: mechanisms and applications.","authors":"Di Chang, Jingrong Xu, Chenhao Yang, Yanli An, Dongfang Liu","doi":"10.1016/j.ijpharm.2026.126707","DOIUrl":"10.1016/j.ijpharm.2026.126707","url":null,"abstract":"<p><p>Vascular calcification (VC), a critical pathological complication in chronic kidney disease, type 2 diabetes mellitus, and atherosclerosis, is also a major risk factor for adverse cardiovascular events. Once considered a passive age-related process, VC is now recognized as a highly dynamic and multifactorial process involving an array of biological events, including oxidative stress, cellular phenotypic differentiation, and disruptions in calcium-phosphate homeostasis, among others. To date, no specific pharmacological therapies for VC have been established. Existing drug candidates in VC clinical trials often exhibit limitations like short half-lives and poor targeting efficiency, and systemic drug administration is limited by low efficacy and a high risk of adverse effects, which hinders clinical translation. In recent years, nanomaterials have emerged as promising therapeutic strategies to mitigate the dynamic pathological process of VC by virtue of microenvironment-responsive release, multi-target synergistic regulation, and precise enrichment at lesion sites, with the potential to overcome barriers to clinical translation. This review consolidates the pathophysiological mechanisms of VC, systematically evaluates recent advances in nanomaterial-based VC therapies, and analyzes future research directions based on existing evidence, with the goal of providing a theoretical foundation and innovative strategies to overcome current clinical barriers in VC management.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126707"},"PeriodicalIF":5.2,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20Epub Date: 2026-01-08DOI: 10.1016/j.ijpharm.2026.126584
Lukáš Veselý , Jan Ryšávka , Radim Štůsek , Behera Susrisweta , Jiří Zeman , Thomas Loerting , Dominik Heger
Freezing and lyophilization are commonly used methods for stabilizing pharmaceutical and biochemical formulations. However, these processes can introduce a variety of freezing-induced stresses that may lead not to stabilization, but rather to the destabilization of active molecules. One of the most significant of these stresses is freezing-induced acidity change, which has been shown to cause protein aggregation, loss of structural integrity, and increased chemical reactivity. While buffers are routinely used in liquid formulations to minimize pH fluctuations, several studies have demonstrated that certain buffers not only fail to maintain pH during freezing but may actively contribute to acidity shifts. In this study, we investigate the effects of cooling rate, initial pH, mannitol concentration, and lyophilization on acidity in glycine and L-histidine buffer systems in the solid state (both frozen and lyophilized) using UV–VIS spectroscopy and differential scanning calorimetry. Our results indicate that the freezing of amino acid buffers causes a slight increase in pH (basification); however, changes in acidity are not solely the consequence of freezing as they also occur during lyophilization. Notably, in L-histidine with mannitol at pH 7, lyophilization induces acidification of up to 4 units − opposite to the direction observed during freezing. Furthermore, we explore the correlation between vitrification of the freeze-concentrated solution and freezing-induced acidity changes, as quantified using the Hammett acidity function (H2-). These findings may inform the rational design of more robust stabilization strategies.
{"title":"Acidity changes in glycine and L-histidine buffers, mannitol, and their mixtures after freezing and lyophilization","authors":"Lukáš Veselý , Jan Ryšávka , Radim Štůsek , Behera Susrisweta , Jiří Zeman , Thomas Loerting , Dominik Heger","doi":"10.1016/j.ijpharm.2026.126584","DOIUrl":"10.1016/j.ijpharm.2026.126584","url":null,"abstract":"<div><div>Freezing and lyophilization are commonly used methods for stabilizing pharmaceutical and biochemical formulations. However, these processes can introduce a variety of freezing-induced stresses that may lead not to stabilization, but rather to the destabilization of active molecules. One of the most significant of these stresses is freezing-induced acidity change, which has been shown to cause protein aggregation, loss of structural integrity, and increased chemical reactivity. While buffers are routinely used in liquid formulations to minimize pH fluctuations, several studies have demonstrated that certain buffers not only fail to maintain pH during freezing but may actively contribute to acidity shifts. In this study, we investigate the effects of cooling rate, initial pH, mannitol concentration, and lyophilization on acidity in glycine and L-histidine buffer systems in the solid state (both frozen and lyophilized) using UV–VIS spectroscopy and differential scanning calorimetry. Our results indicate that the freezing of amino acid buffers causes a slight increase in pH (basification); however, changes in acidity are not solely the consequence of freezing as they also occur during lyophilization. Notably, in L-histidine with mannitol at pH 7, lyophilization induces acidification of up to 4 units − opposite to the direction observed during freezing. Furthermore, we explore the correlation between vitrification of the freeze-concentrated solution and freezing-induced acidity changes, as quantified using the Hammett acidity function (<em>H</em><sub>2-</sub>). These findings may inform the rational design of more robust stabilization strategies.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126584"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20Epub Date: 2026-01-27DOI: 10.1016/j.ijpharm.2026.126614
Nadina Zulbeari , Magnus Jæger Dixen , Sebastian Black , Lau Marold Stolborg , Mads Fahnøe Hansen , Adam Cohen Simonsen , Frederik Wendelboe Lund , René Holm
This study investigated the interfacial behaviors of non-ionic surfactants at the air–liquid and solid–liquid interfaces including the work of adhesion derived from surface tension and contact angle measurements and explored their potential link to the physical stability of pharmaceutical suspensions. Surface tension measurements using pendant drop tensiometry revealed varying capacities of seven non-ionic surfactants to reduce the surface tension of water, with polysorbate 20 achieving the lowest equilibrium surface tension (36.07 ± 1.08 mN/m) and poloxamer 188 the highest (48.89 ± 0.20 mN/m). Contact angle measurements were performed between 0.5 mM, 1 mM, and 2 mM surfactant solutions and thin spin-coated drug films of eight model compounds to assess solid–liquid wettability and calculate the work of adhesion. All surfactant solutions exhibited contact angles below 90°, suggesting favorable spreading on drug compound surfaces, though compound-specific differences in wettability were observed. Some surfactant-drug compound combinations, such as polysorbate 20 with naproxen or TBAJ-876, showed contact angles near 0°, potentially indicating superspreading behavior. The work of adhesion, derived from surface tension and contact angles, generally decreased in the presence of surfactants compared to water, and slightly increased with higher surfactant concentration. Pharmaceutical suspensions with the eight model drug compounds were evaluated for physical stability, assessed by monitoring the particle size profiles for 28 days at 40 °C to assess stabilization efficiency to maintain the sizes of drug particles during storage. While some correlations between low work of adhesion and poor stabilizer performance were noted — such as vitamin E TPGS with bedaquiline and poloxamer 188 with haloperidol — no consistent trend was observed across all surfactants and drug compounds. Most data clustered closely, with outliers offering limited predictive value between interfacial measurements and particle size profiles. These findings therefore suggested that although interfacial energy measurements provided valuable insight into surfactant behavior and solid–liquid interactions, they were not sufficient as standalone predictors of physical stability in pharmaceutical suspensions.
{"title":"Potential correlations between the energies at the solid/liquid interfaces and the physical stability of pharmaceutical suspensions","authors":"Nadina Zulbeari , Magnus Jæger Dixen , Sebastian Black , Lau Marold Stolborg , Mads Fahnøe Hansen , Adam Cohen Simonsen , Frederik Wendelboe Lund , René Holm","doi":"10.1016/j.ijpharm.2026.126614","DOIUrl":"10.1016/j.ijpharm.2026.126614","url":null,"abstract":"<div><div>This study investigated the interfacial behaviors of non-ionic surfactants at the air–liquid and solid–liquid interfaces including the work of adhesion derived from surface tension and contact angle measurements and explored their potential link to the physical stability of pharmaceutical suspensions. Surface tension measurements using pendant drop tensiometry revealed varying capacities of seven non-ionic surfactants to reduce the surface tension of water, with polysorbate 20 achieving the lowest equilibrium surface tension (36.07 ± 1.08 mN/m) and poloxamer 188 the highest (48.89 ± 0.20 mN/m). Contact angle measurements were performed between 0.5 mM, 1 mM, and 2 mM surfactant solutions and thin spin-coated drug films of eight model compounds to assess solid–liquid wettability and calculate the work of adhesion. All surfactant solutions exhibited contact angles below 90°, suggesting favorable spreading on drug compound surfaces, though compound-specific differences in wettability were observed. Some surfactant-drug compound combinations, such as polysorbate 20 with naproxen or TBAJ-876, showed contact angles near 0°, potentially indicating superspreading behavior. The work of adhesion, derived from surface tension and contact angles, generally decreased in the presence of surfactants compared to water, and slightly increased with higher surfactant concentration. Pharmaceutical suspensions with the eight model drug compounds were evaluated for physical stability, assessed by monitoring the particle size profiles for 28 days at 40 °C to assess stabilization efficiency to maintain the sizes of drug particles during storage. While some correlations between low work of adhesion and poor stabilizer performance were noted — such as vitamin E TPGS with bedaquiline and poloxamer 188 with haloperidol — no consistent trend was observed across all surfactants and drug compounds. Most data clustered closely, with outliers offering limited predictive value between interfacial measurements and particle size profiles. These findings therefore suggested that although interfacial energy measurements provided valuable insight into surfactant behavior and solid–liquid interactions, they were not sufficient as standalone predictors of physical stability in pharmaceutical suspensions.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126614"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20DOI: 10.1016/j.ijpharm.2026.126672
Sudipta Mallick, Pankaj Sharma, Tejabhiram Yadavalli, Ram Koganti, Sudhanshu Kumar Singh, Kailee Yoshimura, Divya Kapoor, Yogesh Sutar, Joseph S Adams, Manjusha Annaji, Deepak Shukla, Abhijit A Date
Genital herpes (GH) is a persistent sexually transmitted infection primarily caused by herpes simplex virus type 2 (HSV-2). Recently, myricetin (MYR), a natural flavonoid with low aqueous solubility, was shown to target HSV gD protein. Here, using computational tools, we showed that MYR forms a stable complex with HSV gD protein. MYR was well tolerated by HeLa cells (CC50 ∼ 2.5 mM) and showed in vitro antiviral activity of MYR against wild-type HSV-2. The low aqueous solubility of MYR and the possibility of metabolic deactivation limit the delivery of MYR. To overcome these challenges, we encapsulated MYR into nanoparticles (NPs) of pharmaceutically acceptable polycarboxylate polymers such as polyvinyl acetate phthalate (PVAP), hydroxypropyl methyl cellulose phthalate (HPMCP), and Eudragit S100, and these MYR-polycarboxylate NPs (size ≤ 100 nm) showed high colloidal stability and chemical stability of MYR for at least 4 weeks. The MYR-polycarboxylate NPs retained the inherent antioxidant activity of MYR in vitro, and MYR-PVAP-NPs showed the highest antiviral activity in vitro among various MYR-polycarboxylate NPs. We developed an in-situ gelling formulation containing MYR-PVAP-NPs to facilitate intravaginal delivery. The in-situ gelling formulation containing MYR-PVAP-NPs showed excellent antiviral efficacy compared to MYR solution in a mouse model of GH.
{"title":"Topical administration of in situ gelling formulation containing myricetin-polycarboxylate nanoparticles inhibits murine genital herpes infection.","authors":"Sudipta Mallick, Pankaj Sharma, Tejabhiram Yadavalli, Ram Koganti, Sudhanshu Kumar Singh, Kailee Yoshimura, Divya Kapoor, Yogesh Sutar, Joseph S Adams, Manjusha Annaji, Deepak Shukla, Abhijit A Date","doi":"10.1016/j.ijpharm.2026.126672","DOIUrl":"10.1016/j.ijpharm.2026.126672","url":null,"abstract":"<p><p>Genital herpes (GH) is a persistent sexually transmitted infection primarily caused by herpes simplex virus type 2 (HSV-2). Recently, myricetin (MYR), a natural flavonoid with low aqueous solubility, was shown to target HSV gD protein. Here, using computational tools, we showed that MYR forms a stable complex with HSV gD protein. MYR was well tolerated by HeLa cells (CC<sub>50</sub> ∼ 2.5 mM) and showed in vitro antiviral activity of MYR against wild-type HSV-2. The low aqueous solubility of MYR and the possibility of metabolic deactivation limit the delivery of MYR. To overcome these challenges, we encapsulated MYR into nanoparticles (NPs) of pharmaceutically acceptable polycarboxylate polymers such as polyvinyl acetate phthalate (PVAP), hydroxypropyl methyl cellulose phthalate (HPMCP), and Eudragit S100, and these MYR-polycarboxylate NPs (size ≤ 100 nm) showed high colloidal stability and chemical stability of MYR for at least 4 weeks. The MYR-polycarboxylate NPs retained the inherent antioxidant activity of MYR in vitro, and MYR-PVAP-NPs showed the highest antiviral activity in vitro among various MYR-polycarboxylate NPs. We developed an in-situ gelling formulation containing MYR-PVAP-NPs to facilitate intravaginal delivery. The in-situ gelling formulation containing MYR-PVAP-NPs showed excellent antiviral efficacy compared to MYR solution in a mouse model of GH.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126672"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20Epub Date: 2026-01-17DOI: 10.1016/j.ijpharm.2026.126597
Fabia Julliana Jorge de Souza , Francisco Alexandrino-Junior , Wógenes Nunes de Oliveira , Euzébio Guimarães Barbosa , Renato Medeiros de Paula , Éverton do Nascimento Alencar , Júlio Abreu Miranda , Maria Cecília Queiroga dos Santos , Mabel Calina de França Paz , Fábio Rocha Formiga , Eryvaldo Sócrates Tabosa do Egito
Ocular diseases, particularly infections such as fungal keratitis, present significant therapeutic challenges due to limited treatment options and low patient compliance. This study aimed to develop and characterize polyvinyl alcohol (PVA)-based hydrogel ophthalmic lenses (HOLs) incorporating amphotericin B (AmB) for potential use in treating fungal ocular infections. A central composite design (CCD) was employed to optimize the formulation, which was then evaluated for thickness, swelling degree, drug loading, release kinetics, and physicochemical properties via Fourier-transform infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), and molecular dynamics simulations (MDS). Additional assessments included mass loss under physiological conditions (37 °C) and in vitro antifungal activity against clinical strains of Candida albicans, Candida parapsilosis, and Candida tropicalis. The CCD enabled precise mathematical modeling of swelling behavior, resulting in HOLs with controlled thickness (0.162 ± 0.011 mm to 0.265 ± 0.018 mm) and suitable hydration profiles. The results from FTIR and PXRD analyses confirmed effective crosslinking and indicated the presence of AmB in an amorphous or molecular dispersed state. After 30 days in artificial tear fluid (pH ∼ 7.4), the lenses exhibited low mass loss (4.4 ± 2.7%), supporting their structural stability. Release studies demonstrated a sustained and controlled AmB release profile, with cumulative release ranging from approximately 25% to 58% in the first 24 h among the tested formulations, consistent with the MDS findings that showed strong interactions between AmB, PVA, and sodium trimetaphosphate (STMP). The HOLs demonstrated antifungal efficacy, particularly against Candida parapsilosis. Overall, the developed PVA-based HOLs offer a promising platform for sustained ocular delivery of AmB in treatment of fungal infections.
{"title":"Eyes on the future: PVA-hydrogel lenses as a platform for amphotericin B ocular delivery","authors":"Fabia Julliana Jorge de Souza , Francisco Alexandrino-Junior , Wógenes Nunes de Oliveira , Euzébio Guimarães Barbosa , Renato Medeiros de Paula , Éverton do Nascimento Alencar , Júlio Abreu Miranda , Maria Cecília Queiroga dos Santos , Mabel Calina de França Paz , Fábio Rocha Formiga , Eryvaldo Sócrates Tabosa do Egito","doi":"10.1016/j.ijpharm.2026.126597","DOIUrl":"10.1016/j.ijpharm.2026.126597","url":null,"abstract":"<div><div>Ocular diseases, particularly infections such as fungal keratitis, present significant therapeutic challenges due to limited treatment options and low patient compliance. This study aimed to develop and characterize polyvinyl alcohol (PVA)-based hydrogel ophthalmic lenses (HOLs) incorporating amphotericin B (AmB) for potential use in treating fungal ocular infections. A central composite design (CCD) was employed to optimize the formulation, which was then evaluated for thickness, swelling degree, drug loading, release kinetics, and physicochemical properties via Fourier-transform infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), and molecular dynamics simulations (MDS). Additional assessments included mass loss under physiological conditions (37 °C) and <em>in vitro</em> antifungal activity against clinical strains of <em>Candida albicans</em>, <em>Candida parapsilosis</em>, and <em>Candida tropicalis.</em> The CCD enabled precise mathematical modeling of swelling behavior, resulting in HOLs with controlled thickness (0.162 ± 0.011 mm to 0.265 ± 0.018 mm) and suitable hydration profiles. The results from FTIR and PXRD analyses confirmed effective crosslinking and indicated the presence of AmB in an amorphous or molecular dispersed state. After 30 days in artificial tear fluid (pH ∼ 7.4), the lenses exhibited low mass loss (4.4 ± 2.7%), supporting their structural stability. Release studies demonstrated a sustained and controlled AmB release profile, with cumulative release ranging from approximately 25% to 58% in the first 24 h among the tested formulations, consistent with the MDS findings that showed strong interactions between AmB, PVA, and sodium trimetaphosphate (STMP). The HOLs demonstrated antifungal efficacy, particularly against <em>Candida parapsilosis.</em> Overall, the developed PVA-based HOLs offer a promising platform for sustained ocular delivery of AmB in treatment of fungal infections.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126597"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20Epub Date: 2026-01-26DOI: 10.1016/j.ijpharm.2026.126619
Xuerui Ma, Jiajia Jia, Jiajie Chen, Xiaoqi An, Tingting Chen, Ji Li, Dongkai Wang
Cetirizine eye drops provide rapid symptom relief in allergic conjunctivitis but are limited by short precorneal residence and frequent dosing. This study aimed to develop and compare dual pH- and temperature-responsive in situ gels incorporating Poloxamer and two Carbopol grades to enhance ocular retention and improve therapeutic efficacy. Two formulations were prepared using Poloxamer 407/188 with either Carbopol AA-1 (AA-Gel) or Carbopol TR-1(TR-Gel). Sol–gel transition, microstructure, rheology, erosion, drug release, irritation, precorneal retention, and pharmacodynamic performance were evaluated. The two Carbopol grades generated distinct gel networks, with the TR- Gel forming thicker structural struts, exhibiting higher viscosity, greater resistance to dilution, slower erosion, prolonged precorneal retention, and more sustained cetirizine release. In vivo, the TR-Gel reduced scratching behavior, inflammatory cytokines, and histopathological damage compared to both the AA-Gel and commercial eye drops, without causing ocular irritation. The dual-responsive behavior and Carbopol-dependent network architecture enhanced the stability, retention, and pharmacodynamic performance of cetirizine in situ gels. The TR-Gel, in particular, shows promise as a patient-friendly and more effective alternative to conventional eye drops for managing allergic conjunctivitis.
{"title":"Temperature- and pH-responsive cetirizine hydrochloride in situ gels for enhanced ocular delivery in allergic conjunctivitis","authors":"Xuerui Ma, Jiajia Jia, Jiajie Chen, Xiaoqi An, Tingting Chen, Ji Li, Dongkai Wang","doi":"10.1016/j.ijpharm.2026.126619","DOIUrl":"10.1016/j.ijpharm.2026.126619","url":null,"abstract":"<div><div>Cetirizine eye drops provide rapid symptom relief in allergic conjunctivitis but are limited by short precorneal residence and frequent dosing. This study aimed to develop and compare dual pH- and temperature-responsive in situ gels incorporating Poloxamer and two Carbopol grades to enhance ocular retention and improve therapeutic efficacy. Two formulations were prepared using Poloxamer 407/188 with either Carbopol AA-1 (AA-Gel) or Carbopol TR-1(TR-Gel). Sol–gel transition, microstructure, rheology, erosion, drug release, irritation, precorneal retention, and pharmacodynamic performance were evaluated. The two Carbopol grades generated distinct gel networks, with the TR- Gel forming thicker structural struts, exhibiting higher viscosity, greater resistance to dilution, slower erosion, prolonged precorneal retention, and more sustained cetirizine release. <em>In vivo</em>, the TR-Gel reduced scratching behavior, inflammatory cytokines, and histopathological damage compared to both the AA-Gel and commercial eye drops, without causing ocular irritation. The dual-responsive behavior and Carbopol-dependent network architecture enhanced the stability, retention, and pharmacodynamic performance of cetirizine in situ gels. The TR-Gel, in particular, shows promise as a patient-friendly and more effective alternative to conventional eye drops for managing allergic conjunctivitis.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126619"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20Epub Date: 2026-01-14DOI: 10.1016/j.ijpharm.2026.126593
A. De Man , B. Van Snick , T. Verbeek , M. Otava , A. Kumar , C. Vervaet , V. Vanhoorne , T. De Beer
The current study investigated the differences in volumetric twin-screw feeding behaviour of 15 commonly known oral solid dosage powder materials between two loss-in-weight feeders, differing in scale. Principal Component Analysis (PCA) was applied to study the importance of material properties on various volumetric feeding output parameters. In addition, the developed PCA model was used to explore material properties that could explain observed differences in screw filling as a function of the screw speed per feeder. To study changes in the importance of material properties of various powder materials between two loss-in-weight feeding systems, multiple Partial Least Squares (PLS) regression models were developed. These PLS models focused on predicting screw filling, feeding capacity decay and short-term feeding variability. Overall, the difference in overhead pressure between both studied feeders appeared to affect the importance of material properties, mostly for the maximum screw filling. The developed models highlighted the importance of material properties on twin-screw feeding behaviour per loss-in-weight feeder and will support future research on developing a surrogate material identification and selection methodology.
{"title":"Exploring twin-screw feeding behaviour across different loss-in-weight feeders","authors":"A. De Man , B. Van Snick , T. Verbeek , M. Otava , A. Kumar , C. Vervaet , V. Vanhoorne , T. De Beer","doi":"10.1016/j.ijpharm.2026.126593","DOIUrl":"10.1016/j.ijpharm.2026.126593","url":null,"abstract":"<div><div>The current study investigated the differences in volumetric twin-screw feeding behaviour of 15 commonly known oral solid dosage powder materials between two loss-in-weight feeders, differing in scale. Principal Component Analysis (PCA) was applied to study the importance of material properties on various volumetric feeding output parameters. In addition, the developed PCA model was used to explore material properties that could explain observed differences in screw filling as a function of the screw speed per feeder. To study changes in the importance of material properties of various powder materials between two loss-in-weight feeding systems, multiple Partial Least Squares (PLS) regression models were developed. These PLS models focused on predicting screw filling, feeding capacity decay and short-term feeding variability. Overall, the difference in overhead pressure between both studied feeders appeared to affect the importance of material properties, mostly for the maximum screw filling. The developed models highlighted the importance of material properties on twin-screw feeding behaviour per loss-in-weight feeder and will support future research on developing a surrogate material identification and selection methodology.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126593"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20Epub Date: 2026-01-14DOI: 10.1016/j.ijpharm.2026.126592
Mona Mohammadkhani, Janusz Kozinski, Leila Pakzad
Optimizing pulmonary drug delivery requires a detailed understanding of aerosol–mucus interactions, particularly under pathological conditions such as chronic obstructive pulmonary disease (COPD), where mucus composition, rheology, and surface properties are markedly altered. This study investigated how modulating the drug–mucus contact angle—a surrogate for mucosal wettability—affects deposition outcomes in pressurized metered-dose inhalers (pMDIs). A realistic mouth–throat (MT) model was fabricated and coated with artificial pulmonary mucus, then experimentally characterized to establish a baseline contact angle of 22.5°. This baseline value was implemented in the numerical model, which was validated against in vitro Next Generation Impactor (NGI) data and subsequently extended to simulate contact angles of 40° and 60°, representing reduced wettability scenarios typical of severe COPD.
Our findings showed that disease-altered wettability conditions (θ = 60°) increased overall drug deposition by approximately 13.4 % compared with the healthy airway condition (θ = 22.5°), underscoring the adhesive contribution to droplet retention. Simulations further revealed that oropharyngeal deposition is highly sensitive to mucus wettability: lower interfacial tension promoted complete spreading and mucosal absorption, whereas higher interfacial tension led to droplet rebound, limited transfer, and downstream re-entrainment. Collectively, these findings provide mechanistic insight into how controlling drug–mucus interfacial characteristics can improve aerosol delivery in disease-compromised airways.
{"title":"Mucoadhesion-controlled deposition and impaction dynamics of inhaled drugs in artificial mucus-coated airways: a coupled experimental–computational study","authors":"Mona Mohammadkhani, Janusz Kozinski, Leila Pakzad","doi":"10.1016/j.ijpharm.2026.126592","DOIUrl":"10.1016/j.ijpharm.2026.126592","url":null,"abstract":"<div><div>Optimizing pulmonary drug delivery requires a detailed understanding of aerosol–mucus interactions, particularly under pathological conditions such as chronic obstructive pulmonary disease (COPD), where mucus composition, rheology, and surface properties are markedly altered. This study investigated how modulating the drug–mucus contact angle—a surrogate for mucosal wettability—affects deposition outcomes in pressurized metered-dose inhalers (pMDIs). A realistic mouth–throat (MT) model was fabricated and coated with artificial pulmonary mucus, then experimentally characterized to establish a baseline contact angle of 22.5°. This baseline value was implemented in the numerical model, which was validated against in vitro Next Generation Impactor (NGI) data and subsequently extended to simulate contact angles of 40° and 60°, representing reduced wettability scenarios typical of severe COPD.</div><div>Our findings showed that disease-altered wettability conditions (θ = 60°) increased overall drug deposition by approximately 13.4 % compared with the healthy airway condition (θ = 22.5°), underscoring the adhesive contribution to droplet retention. Simulations further revealed that oropharyngeal deposition is highly sensitive to mucus wettability: lower interfacial tension promoted complete spreading and mucosal absorption, whereas higher interfacial tension led to droplet rebound, limited transfer, and downstream re-entrainment. Collectively, these findings provide mechanistic insight into how controlling drug–mucus interfacial characteristics can improve aerosol delivery in disease-compromised airways.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126592"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-20Epub Date: 2026-01-10DOI: 10.1016/j.ijpharm.2026.126586
Salvatore Zarrella , Elena Wanvig i Dot , J. Axel Zeitler , Timothy M. Korter
Terahertz time-domain spectroscopy (THz-TDS) is a non-destructive, high-resolution method that probes low-frequency vibrational modes and intermolecular interactions between the microwave and infrared regions inaccessible by other spectroscopic methods. The technique is established in the pharmaceutical sciences and is now spreading to other areas in need of an extensive understanding of material properties. Despite the growth in THz applications, measurements are still confined to specialized laboratories. This tutorial seeks to provide a practical standard operating procedure for taking transmission measurements of compacted powders and is designed for new users across disciplines. We describe sample preparation, spectrometer configuration, data acquisition, signal processing, quantitative analysis, and troubleshooting. Emphasis is placed on practical strategies such as selecting appropriate diluents, ensuring homogeneous sample mixing, optimizing pellet thickness, aligning the optical setup, and handling spectral artifacts like Fabry–Pérot etalons. Additionally, the tutorial guides users through data transformation using FFT and apodization techniques to extract accurate optical constants such as refractive index and absorption coefficients. By consolidating best practices and minimizing technical barriers, this resource aims to make THz spectroscopy more accessible and reproducible for researchers across disciplines.
{"title":"From powder to spectrum: A tutorial of terahertz transmission time-domain spectroscopy","authors":"Salvatore Zarrella , Elena Wanvig i Dot , J. Axel Zeitler , Timothy M. Korter","doi":"10.1016/j.ijpharm.2026.126586","DOIUrl":"10.1016/j.ijpharm.2026.126586","url":null,"abstract":"<div><div>Terahertz time-domain spectroscopy (THz-TDS) is a non-destructive, high-resolution method that probes low-frequency vibrational modes and intermolecular interactions between the microwave and infrared regions inaccessible by other spectroscopic methods. The technique is established in the pharmaceutical sciences and is now spreading to other areas in need of an extensive understanding of material properties. Despite the growth in THz applications, measurements are still confined to specialized laboratories. This tutorial seeks to provide a practical standard operating procedure for taking transmission measurements of compacted powders and is designed for new users across disciplines. We describe sample preparation, spectrometer configuration, data acquisition, signal processing, quantitative analysis, and troubleshooting. Emphasis is placed on practical strategies such as selecting appropriate diluents, ensuring homogeneous sample mixing, optimizing pellet thickness, aligning the optical setup, and handling spectral artifacts like Fabry–Pérot etalons. Additionally, the tutorial guides users through data transformation using FFT and apodization techniques to extract accurate optical constants such as refractive index and absorption coefficients. By consolidating best practices and minimizing technical barriers, this resource aims to make THz spectroscopy more accessible and reproducible for researchers across disciplines.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126586"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号