Journal of Pharmaceutical Innovation最新文献

Purpose

The purpose of the present work is to improve the brain uptake by developing and characterizing an in-situ nasal formulation of Edaravone nanosuspension.

Methods

A quality-by-design approach was comprehended for the understanding of the influence of formulation and process parameters on the quality aspects. The solvent-antisolvent method was employed for the fabrication of nanosuspension. In the study, the influence of various process and formulation parameters on the particle size and % drug content were investigated. Optimization was carried out using response surface methodology. To improve the stability of the nanosuspension, lyophilization using trehalose was performed. Lyophilized powder was incorporated into in-situ nasal gel.

Results

The formulation with a 1:1 drug-polymer ratio and the lowest Tween 80 concentration was found to meet the criteria for an optimum formulation. The lyophilized powder of nanosuspension was subjected to the various physical characterizations showed the inclusion of drug molecule into the polymer. Lyophilized powder containing in-situ formulation was demonstrated to have adequate mucoadhesion, prolonged in vitro release, 10% increment in nasal permeation flux and good rheological properties. In-vivo studies revealed 12% increment in brain bioavailability and 9% increment in brain Cmax in comparison with marketed injectable formulation.

Conclusion

This research highlights the depth of understanding achieved through a well-designed study based on the QbD approach.

Background

Correct pressurized metered dose inhaler (pMDI) technique is essential for optimal lung deposition. Although spacer devices are recommended for patients with poor inhaler technique, access and affordability remain barriers. The current research evaluated the in-vitro salbutamol aerosol delivery characteristics through a novel card-based spacer (the MDI Plus^®), compared to a commercial plastic spacer (AeroChamber Plus^®).

Method

An Andersen cascade impactor was used to assess the total emitted dose (TED) and aerodynamic particle size distribution (APSD) of salbutamol emitted from pMDI alone and pMDI attached to two different spacers: the MDI Plus^® and AeroChamber Plus^®. Key APSD metrics included fine particle dose (FPD), fine particle fraction (FPF), mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). Salbutamol samples were quantified using a validated high-performance liquid chromatography method.

Results

pMDI alone produced the highest total emitted dose (TED: 368.35 ± 20.26 µg), significantly exceeding AeroChamber Plus^® (207.32 ± 6.39 µg) and MDI Plus^® (193.53 ± 3.18 µg) (p < 0.001). MDI Plus^® had the highest fine particle fraction (FPF: 71.41 ± 3.12%) compared to AeroChamber Plus^® (58.75 ± 0.89%) and pMDI alone (24.73 ± 2.74%), p = 0.051. MMAD was lowest with MDI Plus^® (3.88 ± 0.02 μm), suggesting smaller, more respirable particles. Both spacers reduced upper airway deposition relative to pMDI alone.

Conclusion

The current findings support the utility of spacers in optimizing pMDI aerosol delivery. The MDI Plus^® performed comparably to the AeroChamber Plus^® in terms of emission and particle characteristics. Its affordability and disposable design may enhance accessibility, particularly in resource-limited settings.

Acrylamide (ACR) has gained worldwide attention as a thermal process contaminant because of its neurotoxic actions and widespread presence. Prolonged exposure to ACR results in the degeneration of neuronal cells, loss of motor function, and potential impairment of antioxidant defence systems, especially during brain development. The widespread exposure and neurotoxic effects of acrylamide, there is an urgent need​ to identify natural compounds capable of mitigating its detrimental impact on the nervous system. Therefore, this study aimed to determine the neuroprotective effect of swertiamarin (SWE) on ACR-induced neurotoxicity in zebrafish larvae. Zebrafish larvae at 3 days post-fertilisation (dpf) were exposed to 0.75 mM ACR for 3 days to induce neurotoxicity and co-treated with SWE (100 µM) to evaluate its potential neuroprotective effects. All behavioural and biochemical assays, including locomotor activity, glutathione levels, antioxidant enzyme activity, and acetylcholinesterase function in the head region, were conducted at 6 days post-fertilization (dpf). ACR exposure disrupted glutathione redox balance in zebrafish larvae, and subsequent SWE treatment significantly restored this balance, which is essential for acrylamide detoxification and clearance. Furthermore, it reduced the expression of pro-inflammatory cytokines, including tnf-α, il-1β, and il-6, in the zebrafish larvae head, alleviated oxidative stress, and improved synaptic vesicle cycling. Motor responses were partially restored, suggesting an improvement in neuronal function. In conclusion, this study demonstrates that SWE exhibits neuroprotective effects against acrylamide-induced damage by modulating neuroinflammation, synaptic function, and oxidative stress. These results support the potential of SWE as a treatment option for neurodegenerative illnesses linked to oxidative stress.

Purpose

Sustained and simultaneous delivery of antibiotics and flavonoids using nanoformulations represents an innovative therapeutic approach against drug-resistant bacteria. In the present study, we encapsulated levofloxacin and baicalin, a plant flavonoid, into chitosan nanoparticles using the ionic gelation technique and investigated the effects of the dual drug-loaded nanoparticles on virulence factors and toxin-producing genes in P. aeruginosa PAO1.

Methods

The physicochemical properties of Bai-Lvx-CsNPs were investigated using various characterization techniques. Furthermore, the effects of Bai-Lvx-CsNPs on P. aeruginosa growth, virulence traits, and toxin-associated genes were assessed.

Results

Characterization of Bai-Lvx-CsNPs revealed that the particles were spherical, with an average size of 69.26 ± 17.8 nm. The release kinetics of baicalin and levofloxacin from Bai-CsNPs and Lvx-CsNPs demonstrated a gradual and sustained release profile. The highest growth inhibitory activity was observed for Bai-Lvx-CsNPs, with a MIC value of 1.56 mg/mL. Furthermore, the MBC value of Bai-Lvx-CsNPs was determined to be 12.5 mg/mL. In addition, cells treated with ½ MIC of dual-loaded nanoparticles exhibited the highest DNA leakage (24.08 ± 0.43 ng/µL). A reduction in LasA protease activity and pyocyanin production to 48.92 ± 5.72% and 13.33 ± 4.57%, respectively, confirmed the efficient effect of Bai-Lvx-CsNPs in suppressing secreted virulence factors. Treatment with the dually encapsulated nanoparticles significantly reduced swarming motility and the metabolic activity of bacterial biofilm to 1.7 ± 1.6% and 19.09 ± 0.33%, respectively. Furthermore, qPCR analysis showed the greatest reduction in the expression level of the toxA and exoS genes in P. aeruginosa PAO1 following treatment with Bai-Lvx-CsNPs, which decreased to 0.37 ± 0.05 and 0.45 ± 0.07 folds, respectively.

Conclusion

Collectively, these findings highlight the promising antivirulence activity of Bai-Lvx-CsNPs against P. aeruginosa PAO1. Bai-Lvx-CsNPs not only inhibit bacterial growth but also effectively suppress multiple virulence traits, highlighting their potential as a novel therapeutic strategy for the management P. aeruginosa infections. Future in vivo studies are warranted to validate their effectiveness and explore their applicability as alternative or adjunctive treatments against this pathogen.

Background

Developing effective topical therapies for inflammation remains a challenge due to the limitations of conventional treatments, including poor bioavailability, instability, and systemic side effects. Here, we present a novel Ipomoea cairica loaded silver nanoparticle (AgNP) nanogel, integrating natural anti-inflammatory phytochemicals with nanotechnology under a Quality by Design (QbD) framework to achieve enhanced stability, targeted delivery, and therapeutic efficacy.

Methods

AgNPs were synthesized using aqueous Ipomoea cairica leaf extract and incorporated into a nanogel by using Carbopol 940 as the gelling agent. The formulation was optimized using Central Composite Design (CCD) for critical factors such as pH, viscosity, and spreadability. Comprehensive characterization included analysis of particle size, zeta potential, PDI, physicochemical properties, in-vitro release, ex-vivo skin permeation, and in-vivo anti-inflammatory efficacy. Histopathological analysis and stability studies further evaluated formulation performance.

Results

Synthesized AgNPs revealed an average particle size of 98 nm and a zeta potential of -30.35 mV with PDI of 0.3. The optimized nanogel exhibited homogeneity, stability, neutral pH (7.21), viscosity of 706 cps, and spreadability of 53.33 g.cm/s, ensuring skin compatibility. In-vitro release study revealed 77.20% sustained drug release, while ex-vivo skin permeation reached 85.95% demonstrating efficient drug penetration. In-vivo studies confirmed significant anti-inflammatory activity, with a 90.14% reduction in carrageenan-induced edema. Histopathological analysis confirmed minimal tissue damage in the nanogel-treated group compared to control. These findings highlight the synergistic effect of plant phytochemicals and nanogel delivery on AgNP stability and anti-inflammatory efficacy.

Conclusion

The optimized Ipomoea cairica-derived AgNP nanogel demonstrated desirable physicochemical properties, sustained release, efficient skin permeation, and significant anti-inflammatory efficacy. Guided by a QbD approach, this nanogel represents a promising and stable topical delivery system for effective inflammation management.

Graphical Abstract

Background

Artificial Intelligence (AI) is becoming a game-changer in pharmaceutical sciences, especially in drug formulation. Traditional methods of formulation often face challenges such as long timelines, high costs, and repeated trial-and-error processes.

Insights

AI offers solutions by using smart algorithms to speed up development, reduce failures, and improve precision. Machine learning techniques, including neural networks, support vector machines, and reinforcement learning, are being used to predict the best excipients, check drug–drug interactions, improve stability, and even suggest personalized dosages. These tools help researchers make better decisions and cut down on unnecessary experiments. Several AI-driven platforms like IBM Watson, Atomwise, and Schrödinger are already supporting drug discovery and formulation. They combine with existing processes to make workflows more reliable and efficient. Still, challenges remain. Issues with the quality and availability of data, limited computing resources, and regulatory concerns can slow down wider adoption. In addition, questions around ethics and the need for AI systems to be transparent and interpretable are important for building trust. Looking ahead, AI has the potential to transform formulation by integrating omics data, monitoring patients in real time, and creating adaptive formulations that respond to individual needs. Collaboration between pharmacists, AI specialists, and regulators will be essential to make this vision a reality.

Conclusion

AI is paving the way toward faster, cheaper, and more tailored drug development. With continued innovation, it is set to play an indispensable role in pharmaceutical formulation and the advancement of personalized medicine.

Background

Lilium Polyphyllum D. Don ex Royle (Himalayan lily) has long been valued in traditional medicine for managing pain, rheumatism, bronchitis, and intermittent fever. Despite its ethnomedicinal relevance, robust scientific evidence supporting its anti-inflammatory and analgesic effects remains limited.

Objectives

This study aims to validate the traditional anti-inflammatory and analgesic uses of L. polyphyllum bulb by characterizing its phytochemical constituents and elucidating the underlying mechanisms of action through integrated in silico, in vitro and in vivo approaches.

Methods

LC-MS/MS and GC-MS analyses were conducted for the most bioactive chloroform (Chl-fr) and ethyl acetate fractions (EtOAc-fr) respectively. Toxicity was assessed via fibroblast viability, brine shrimp lethality, and acute in vivo testing up to 2400 mg/kg, supported by SwissADMET predictions. Anti-inflammatory effects were determined using chemiluminescence and carrageenan-induced paw edema models, while antinociceptive activity was evaluated through acetic acid-induced writhing and hot plate assays. Molecular docking was performed to explore interactions of identified compounds with myeloperoxidase (MPO) and P2X purinergic receptor 7 (P2X7R).

Results

LCMS/MS and GC-MS analyses of Chl-fr and EtOAc-fr identified 55 bioactive compounds, including phenolic acids, glycosides, alkaloids, flavonoids, and fatty acid esters. The Cr. MeOH-Ext and fractions were non-toxic in fibroblast cells, brine shrimp assay, and in vivo up to 2400 mg/kg, with SwissADMET predictions further supporting their safety profile. The in vitro anti-inflammatory results revealed that Chl-fr, EtOAc-fr, and n-Hex-fr exhibited significant inhibition of oxidative burst for whole blood. In carrageenan-induced anti-inflammatory test, significant decrease in paw edema was observed at 50 and 100 mg/kg for Cr. MeOH-Ext and at 100 mg/kg for n-Hex-fr, Chl-fr and EtOAc-fr. In abdominal constriction test, EtOAc-fr at 50 and 100 mg/kg significantly reduced abdominal writhing followed by n-Hex-fr, Cr. MeOH-Ext, and Chl-fr. In hot plate test, the latency time was significantly increased at 100 mg by EtOAc-fr followed by Chl-fr, and n-Hex-fr. Molecular docking analysis revealed that the identified compounds exhibit strong binding affinities with MPO and P2X7R, further supporting their potential anti-inflammatory and antinociceptive mechanisms.

Conclusion

To our knowledge, this study provides the first comprehensive characterization of the phytochemical profiles of chloroform and ethyl acetate fractions of L. polyphyllum bulb, demonstrating significant analgesic and anti-inflammatory potential that scientifically validate the ethnomedicinal applications in pain and inflammation.

Purpose

In this study, we assessed the effectiveness of micelle solutions of essential oil from Origanum onites L. against clinical strains of Acinetobacter baumannii isolated from intensive care units. The monoterpene p-cymene is also evaluated as a promising mediator targeting A. baumannii AbaR and TnpA by using molecular docking analysis.

Methods

Four strains of A. baumannii were molecularly identified; the oil was examined using gas chromatography/mass spectrometry; MIC was determined using the sonicated method; and the inhibitory zones were read using the well agar diffusion method in comparison to colistin. Using AutoDock Vina, a molecular docking analysis was conducted.

Results

Micelle-homogenous solutions of the oil showed low minimum inhibitory concentrations against A. baumannii (Ab OR792201, OR792204, OR792202, and OR792203), ranging from 0.20% to 0.39% v/v. Carvacrol was the major component of O. onites essential oil, accounting for 76.67% of the total, followed by p-cymene at 7.77%. According to the AbaR and TnpA proteins' molecular docking, the ligand was detected in the active site and had conformations that would allow it to create connections. The hydrophobic contacts between the proteins and p-cymene showed that there were eight different hydrophobic interactions between the ligand and TnpA and six between the ligand and AbaR.

Conclusion

The findings of the study indicated that the chemical components of O. onites essential oil had a strong ability to eliminate the highly lethal A. baumannii, which is encouraging. Molecular docking research also demonstrated the potential for interactions between p-cymene and A. baumannii resistance-related proteins.

Purpose

Ebastine, a BCS Class II medication, serves as an antihistamine for treating various allergic reactions. However, its poor aqueous solubility and low oral bioavailability lead to extensive first-pass hepatic metabolism, significantly limiting its therapeutic effectiveness. To address these limitations, the current study aimed to develop and evaluate a nanofiber-based transdermal gel formulation to enhance Ebastine delivery through the skin.

Methods

Ebastine-loaded nanofibers were prepared using the electrospinning method and optimized with a “Box-Behnken experimental design.” The optimized formulation was incorporated into a gel for transdermal application. The formulation was evaluated using Scanning Electron Microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), in vitro drug release performed using a dialysis membrane, and ex vivo permeation tested through goat skin. Additionally, antimicrobial activity against Staphylococcus aureus was evaluated.

Result

The optimized NF5G2 formulation had a uniform diameter of less than 300 nm with a higher drug entrapment efficiency of 95.23%. The cumulative drug release and skin permeation at 12 h were 88.90% and 87.19%, respectively, following the Korsmeyer-Peppas kinetic model. The antimicrobial study showed significant inhibition of S. aureus, a common skin pathogen linked to chronic urticaria.

Conclusion

The developed Ebastine-loaded nanofiber transdermal gel offers improved drug release, high skin permeability, and effective antimicrobial action. This formulation presents a novel and efficient strategy for treating allergic conditions, paving the way for future applications of nanofiber-based therapies in dermatological care.

Graphical Abstract

Purpose

This study explores emerging digital innovations in pharmaceutical manufacturing, as well as the opportunities and challenges they present for product quality and batch release. A secondary objective was to discuss the regulatory compliance of these digital innovations.

Method

A comprehensive systematised literature review was performed using Web of Science, PubMed, and Scopus research databases. Screening of the identified studies was performed using Covidence online software. The Mixed Methods Appraisal Tool (MMAT) was adapted for the risk of bias assessment.

Results

38 studies were included after screening and risk of bias assessment. The thematic analysis identified 5 empirical themes: ‘PAT and RTRT’ ‘AI’, ‘Process Modelling’ ‘IoT’, and ‘Data Management’. The main opportunities identified included prediction of product quality and variability, deviation root cause analysis, real-time process monitoring, and adaptive control to prevent out of specification products. This study didn’t identify any regulatory challenges to these technologies, however challenges included a lack of personnel with the required technical expertise, data security risks, validation challenges, and potential for inaccuracy.

Conclusions

Emerging digital technologies are being used to support pharmaceutical quality. A review of current guidance did not uncover any regulatory obstacles to theimplementation of the identified technologies, once part of the registered manufacturing process. More opportunities than challenges were identified in the literature. Based on this study, we propose a responsible strategy for future digital innovation implementation and conclude that there is value in (1) Adopting digital innovations in pharmaceutical manufacturing and (2) Supporting digital education for QPs and other quality professionals in pharmaceutical manufacturing.