International Journal of Pharmaceutics最新文献

{"title":"Comparative performance study of paperboard disposable spacers versus commercial valved holding chambers for aerosol delivery","authors":"","doi":"10.1016/j.ijpharm.2024.124774","DOIUrl":"10.1016/j.ijpharm.2024.124774","url":null,"abstract":"<div><h3>Purpose</h3><div>The aim of this study is to evaluate and compare the performance, for the administration of fluticasone propionate with a pressurized metered-dose inhaler (pMDI), of two low-tech paperboard spacers versus two commercially available valved holding chambers (VHC).</div></div><div><h3>Methods</h3><div>According to the Canadian standard CAN/CSA-Z264.1–02, total emitted dose (TED) and aerodynamic size distribution were measured for the pMDI in combination with 4 different spacers: a homemade paper cup spacer, the DispozABLE® paperboard spacer, the AeroChamber Plus® plastic VHC, and the Vortex® aluminium VHC.</div></div><div><h3>Results</h3><div>The two disposable paperboard spacers had a lower TED compared to the aluminium VHC, but delivered more than 2.5 times the dose of fluticasone than the commercial plastic VHC. The 3 antistatic devices (<em>i.e.</em> the aluminium VHC, the paperboard DispozABLE® spacer and the paper cup spacer) delivered a significantly higher dose of fine particles than the less antistatic plastic VHC. Their fine particle fraction was statistically similar to that obtained with pMDI without spacer. This respirable fraction ensures an optimal therapeutic effect. All spacers limited the flow of coarse particles, thus avoiding adverse effects on the trachea and oropharynx.</div></div><div><h3>Conclusion</h3><div>We have shown that inexpensive and low-tech paperboard spacers are interesting alternatives for the administration of aerosols<em>.</em></div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panax notoginseng saponins and acetylsalicylic acid co-delivered liposomes for targeted treatment of ischemic stroke.","authors":"Hao Cui, Yanchi Liu, Ying Yu, Dong Lv, Sha Ma, Mingju Gao, Ye Yang, Cheng Yuan, Yuan Liu, Chengxiao Wang","doi":"10.1016/j.ijpharm.2024.124782","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124782","url":null,"abstract":"<p><p>In this study, we aimed to develop brain-targeted co-delivery liposomes for the concurrent delivery of Panax notoginseng saponins (PNS) and acetylsalicylic acid (ASA) for the treatment of ischemic stroke. Within this system, PNS served as a cholesterol substitute, integrating into the phospholipid bilayer of the liposomes, while ASA was encapsulated internally. A poly-2-methacryloyloxyethyl phosphorylcholine (PMPC) polymer was synthesized and incorporated into the liposome surface. This formulation demonstrated an enhanced PNS-loading capacity and facilitated the synchronized delivery of key saponin components. Following PMPC modification, the liposomes exhibited prolonged circulation and improved transport across the blood-brain barrier (BBB) through acetylcholine receptor-mediated pathways. Furthermore, the co-delivery system exhibited enhanced therapeutic efficacy in a rat model of cerebral ischemia-reperfusion injury via the phosphoinositide 3-kinase/protein kinase C pathway. Additional analyses revealed significant effects on the metabolism of neurotransmitters, amino acids, folate, and various other pathways, indicating a multi-faceted therapeutic effect. Overall, this study presents an innovative research strategy for the comprehensive delivery of diverse components in traditional Chinese medicine formulations, highlighting the potential for synergistic treatments that combine traditional Chinese medicine with chemical agents.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346641","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}

{"title":"A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale","authors":"","doi":"10.1016/j.ijpharm.2024.124780","DOIUrl":"10.1016/j.ijpharm.2024.124780","url":null,"abstract":"<div><div>Poor aqueous solubility of preexisting and emerging drug molecules is a common issue faced in the field of pharmaceutics. To address this, particle size reduction techniques, including drug micro- and nanonisation have been widely employed. Nanocrystals (NCs), drug particles with particle sizes below 1 µm, offer high drug content, improved dissolution, and long-acting capabilities. Media milling is the most used method to prepare NCs using of-the-shelf machinery, both at the laboratory and industrial scales. However, early NCs development, especially when limited amounts of the active are available, require the use of milligram-scale media milling. This study introduces a novel mini-scale milling device (Mini-mill) that incorporates temperature control through a water-cooled jacket. The device was used to produce NCs of three model hydrophobic drugs, itraconazole, ivermectin and curcumin, with lowest particle sizes of 162.5 ± 0.4 nm, 178 ± 2 nm, and 116.7 ± 0.7 nm, respectively. Precise control of milling temperature was achieved at 15, 45, and 75°C, with drug dependent particle size reduction trends, with no adverse effects on the milling materials or polymorphic changes in the NCs, as confirmed by calorimetric analysis. Finally, a scale-up feasibility study was carried out in a lab-scale NanoDisp®, confirming that the novel Mini-mills are a material-efficient tool for early formulation development, with potential for scale-up to commercial mills.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of shadowgraph imaging (SGI) particle characterisation data to interpret the impact of varying test conditions on powder dissolution and to develop an automated agglomeration identification method (AIM) in the USP flow-through apparatus","authors":"","doi":"10.1016/j.ijpharm.2024.124778","DOIUrl":"10.1016/j.ijpharm.2024.124778","url":null,"abstract":"<div><div>The aims of this work were 1) to explore the application of shadowgraph imaging (SGI) as a real time monitoring tool to characterize ibuprofen particle behaviour during dissolution testing under various conditions in the USP 4 flow-through apparatus and 2) to investigate the potential to develop an SGI-based automated agglomeration identification method (AIM) for real time agglomerate detection during dissolution testing. The effect of surfactant addition, changes in the drug mass and flow rate, the use of sieved and un-sieved powder fractions, and the use of different drug crystal habits were investigated. Videos at every sampling time point during dissolution were taken and analysed by SGI. The AIM was developed to characterize agglomerates based on two criteria – size and solidity. All detections were confirmed by manual video observation and a reference agglomerate data set. The method was validated under new dissolution conditions with un-sieved particles. Characterisation of particle dispersion behaviour by SGI enabled interpretation of the impact of dissolution test conditions. Higher numbers of early detections reflected greater dissolution rates with increased surfactant concentration, using sieved fraction or plate-shaped crystals, but was impacted by drug mass tested. An AIM was successfully developed and applied to detect agglomerates during dissolution, suggesting potential, with appropriate method development, for application in quality control.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent trends on polycaprolactone as sustainable polymer-based drug delivery system in the treatment of cancer: Biomedical applications and nanomedicine","authors":"","doi":"10.1016/j.ijpharm.2024.124734","DOIUrl":"10.1016/j.ijpharm.2024.124734","url":null,"abstract":"<div><div>The unique properties—such as biocompatibility, biodegradability, bio-absorbability, low cost, easy fabrication, and high versatility—have made polycaprolactone (PCL) the center of attraction for researchers. The derived introduction in this manuscript gives a pretty detailed overview of PCL, so you can first brush up on it. Discussion on the various PCL-based derivatives involves, but is not limited to, poly(ε-caprolactone-co-lactide) (PCL-co-LA), PCL-g-PEG, PCL-g-PMMA, PCL-g-chitosan, PCL-b-PEO, and PCL-g-PU specific properties and their probable applications in biomedicine. This paper has considered examining the differences in the diverse disease subtypes and the therapeutic value of using PCL. Advanced strategies for PCL in delivery systems are also considered. In addition, this review discusses recently patented products to provide a snapshot of recent updates in this field. Furthermore, the text probes into recent advances in PCL-based DDS, for example, nanoparticles, liposomes, hydrogels, and microparticles, while giving special attention to comparing the esters in the delivery of bioactive compounds such as anticancer drugs. Finally, we review future perspectives on using PCL in biomedical applications and the hurdles of PCL-based drug delivery, including fine-tuning mechanical strength/degradation rate, biocompatibility, and long-term effects in living systems.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346643","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}

{"title":"Bioinspired wound dressing: Investigating coelomic fluid-enhanced chitosan/polyvinyl alcohol nanofibers","authors":"","doi":"10.1016/j.ijpharm.2024.124765","DOIUrl":"10.1016/j.ijpharm.2024.124765","url":null,"abstract":"<div><div>The electrospun mats consisting of integrated coelomic fluid (CF) and chitosan (Chs) into polyvinyl alcohol (PVA) nanofibers were produced and evaluated for use as wound dressings. CF was obtained from earthworms (<em>Eisenia andrei (Fetida)</em>) using an electric shock method, while Chs was chemically produced from shrimp chitin and then characterized using titration, Fourier transform infrared (FT-IR) spectroscopy, and viscometry. The wound dressings with different CF contents were evaluated for their antibacterial, antioxidant, and cell viability properties. The dressings infused with CF showed significantly higher antibacterial and antioxidant activity, as well as improved cell viability compared to the control without CF. <em>In vivo</em> studies using adult Wistar albino rats showed that the Chs/PVA/CF wound dressings promoted wound healing and re-epithelialization. Moreover, histological examinations of the injuries coated with Chs/PVA/CF displayed improved re-epithelialization. These results suggest that the Chs/PVA/CF nanofiber has the potential for use as a wound dressing material.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346627","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}

{"title":"Microbubble-laden aerosols improve post-nasal aerosol penetration efficiency in a preterm neonate model","authors":"","doi":"10.1016/j.ijpharm.2024.124772","DOIUrl":"10.1016/j.ijpharm.2024.124772","url":null,"abstract":"<div><div>Nebulized lung surfactant therapy has been a neonatology long-pursued goal. Nevertheless, many clinical trials have yet to show a clear clinical efficacy of nebulized surfactant, which, in part, is due to the technical challenges of delivering aerosols to the lungs of preterm neonates. The study aimed to test microbubbles for improving lung deposition in preterm neonates. An in vitro testing method was developed to replicate the clinical environment; it used a 3D-printed preterm neonate model, connected to a high-flow nasal cannula (HFNC) and a vibrating mesh nebulizer. The flow rate of the HFNC mirrored that used in the clinics (i.e., 4, 6, and 8 L/min). Followingly, the lung penetrations of aerosols with and without microbubbles were compared. The aerodynamic diameter of aerosols with microbubbles (MMAD=1.75 μm) was lower than that of the counterpart (MMAD=2.25 μm). Microbubble-laden aerosols had a significantly higher number of microbubbles that were below 1.0 μm. Microbubble-laden aerosols had dramatically higher lung penetration in the preterm model; lung penetration efficiencies were 30.0, 25.5, and 17.5 % at 4, 6, and 8 L/min, respectively, whereas the lung penetration efficiency for conventionally nebulized aerosols was below 1.25 % in the three flow rates.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Particulate atomisation design methods for the development and engineering of advanced drug delivery systems: A review","authors":"","doi":"10.1016/j.ijpharm.2024.124771","DOIUrl":"10.1016/j.ijpharm.2024.124771","url":null,"abstract":"<div><div>The role and opportunities presented by particulate technologies (due to novel processing methods and advanced materials) have multiplied over the last few decades, leading to promising and ideal properties for drug delivery. For example, the dissolution and bioavailability of poorly soluble drug substances and achieving site- specific drug delivery with a desired release profile are crucial aspects of forming (to some extent) state-of-the-art platforms. Atomisation techniques are intended to achieve efficient control over particle size, improved processing time, improved drug loading efficiency, and the opportunity to encapsulate a broad range of viable yet sensitive therapeutic moieties. Particulate engineering through atomization is accomplished by employing various mechanisms such as air, no air, centrifugal, electrohydrodynamic, acoustic, and supercritical fluid driven processes. These driving forces overcome capillary stresses (e.g., liquid viscosity, surface tension) and transform formulation media (liquid) into fine droplets. More frequently, solvent removal, multiple methods are included to reduce the final size distribution. Nevertheless, a thorough understanding of fluid mechanics, thermodynamics, heat, and mass transfer is imperative to appreciate and predict outputs in real time. More so, in recent years, several advancements have been introduced to improve such processes through complex particle design coupled with quality by-design (QbD) yielding optimal particulate geometry in a predictable manner. Despite these valuable and numerous advancements, atomisation techniques face difficulty scaling up from laboratory scales to manufacturing industry scales. This review details the various atomisation techniques (from design to mechanism) along with examples of drug delivery systems developed. In addition, future perspectives and bottlenecks are provided while highlighting current and selected seminal developments in the field.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346656","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}

{"title":"Optimization of chitosan-gelatin-based 3D-printed scaffolds for tissue engineering and drug delivery applications","authors":"","doi":"10.1016/j.ijpharm.2024.124776","DOIUrl":"10.1016/j.ijpharm.2024.124776","url":null,"abstract":"<div><div>The combination of biocompatible materials and advanced three-dimensional (3D) additive manufacturing technologies holds great potential in the development of finely tuned complex scaffolds with reproducible macro- and micro-structural characteristics for biomedical applications, such as tissue engineering and drug delivery. In this study, biocompatible printable inks based on chitosan, collagen and gelatin were developed and 3D-printed with a pneumatic-based extrusion printer. The printability of various chitosan–gelatin (CS-Gel) hydrogel inks was assessed by evaluating the quality of the printed constructs. The inks required an extrusion pressure of 150 ± 40 MPa with G22 and G25 nozzles for optimal printing. Inks with low chitosan concentrations (&lt;4% w/v) exhibited poor printability, while inks with 4 % w/v chitosan and 1 % w/v gelatin (CG) demonstrated satisfactory extrusion and printing quality. The addition of collagen (0.1 % w/v) to the optimized ink (CGC) did not compromise printability. Post-printing stabilization using KOH produced self-supporting scaffolds with consistent morphological integrity, while weaker bases like NaOH/EtOH and ammonia vapors resulted in lower pore sizes and reduced structural stability. Water evaporation studies showed that neutralized samples had slower evaporation rates due to the strong intermolecular interactions formed during the neutralization process, contributing to a stable crosslinked network. FTIR spectra confirmed the formation of polyelectrolyte complexes in the CS-Gel and CS-Gel-Collagen blends, further enhancing structural stability. Swelling tests indicated that neutralized constructs maintained stability in different pH environments, with KOH-treated samples exhibiting the lowest swelling ratios and the highest structural stability. After optimizing the ink composition, 10 wt% Levofloxacin was loaded in the constructs as a model antibiotic and it’s in vitro release rate was quantified. Drug loading was approximately 4 % for both ink compositions GC and CGC. CG Levo released over 80 % of levofloxacin within the first hour, reaching full release in 24 h, indicating inadequate control, while CGK Levo exhibited slower initial release (55 % in 15 min) followed by stabilized release after 4 h, likely due to controlled diffusion from expanded constructs. These findings demonstrate that the developed hydrogel inks and optimized printing parameters can produce scaffolds suitable for tissue engineering applications. Finally, the cell compatibility of the 3D-printed constructs was confirmed with MTT assay on fibroblasts and the antimicrobial activity of the drug-loaded constructs was tested against E. coli and S. aureus, showing an increase of the bacteria free zone from 8 ± 0.4 mm of the control against E. coli up to 16.4 ± 0.37 mm in the presence of the KOH-treated CG Levo printed construct.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346640","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}

{"title":"Anatomically-detailed segmented representative adult and pediatric nasal models for assessing regional drug delivery and bioequivalence with suspension nasal sprays","authors":"","doi":"10.1016/j.ijpharm.2024.124743","DOIUrl":"10.1016/j.ijpharm.2024.124743","url":null,"abstract":"<div><div>In vitro nasal models can potentially facilitate development and approval of nasal drug products. This study aims to evaluate the potential for using regional deposition measurements from in vitro nasal models to evaluate nasal spray performance across several products. To accomplish this, the posterior regions of six anatomically realistic nasal airway models of adult and pediatric subjects, representing Low (L), Mean (M) and High (H) posterior drug deposition (PD) for each of the two age groups, were segmented with high anatomical precision into five regions of interest. These models were previously developed with the goal of quantifying the range of intersubject variability of PD following administration of inhaled corticosteroids. The in vitro regional drug deposition values were measured for the reference listed drug (RLD) product for triamcinolone acetonide and two corresponding generic (test) nasal spray products, as well as an RLD product for fluticasone furoate nasal spray. In general, the pediatric models mostly demonstrated higher PD compared to the adult models. The majority (&gt;85 %) of PD was confined to the front and the inferior meatus regions. Subsequent population bioequivalence (PBE) analyses of the regional nasal deposition suggested that the anatomical differences among subjects may impact the nasal spray performance across different nasal products.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346625","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}