Pharmaceutical Development and Technology最新文献

Acute alcohol intoxication (AAI) poses serious health risks. Currently, no approved therapy effectively treats both CNS depression and tissue damage in AAI. Standard care, including supportive measures and off-label naloxone, manages respiratory depression but fails to prevent oxidative organ injury. We identified morin (MOR) as a promising candidate for addressing these challenges. Given that MOR is limited by poor water solubility and low oral bioavailability, we developed water-soluble nano-micelle formulations (MOR-Ms) using Kolliphor HS15 (HS15) as a surfactant for intravenous administration. The resulting MOR-Ms exhibited a uniform size of 13.84 ± 0.23 nm and a zeta potential of -9.99 ± 0.21 mV. In vivo, MOR-Ms accelerated alcohol metabolism by enhancing hepatic enzyme activity. In an AAI mouse model induced by intraperitoneal injection of 50% alcohol (10 ml/kg), MOR-Ms (3 mg/kg) significantly shortened the duration of loss of righting reflex (LORR) by 58.01%, which was comparable to the 67.83% reduction achieved by naloxone (1 mg/kg). Furthermore, MOR-Ms markedly lessened tissue damage by decreasing malondialdehyde (MDA) levels (by 32.01% in liver and 53.75% in brain compared to the model group) and boosting antioxidant enzyme activity. These results highlight the potential of MOR-Ms as a promising therapeutic approach for AAI.

Ledipasvir is one of the direct-acting antiviral agents used for treating hepatitis C virus (HCV) infection. To achieve dose reduction and cost-effective therapy, this study aimed to enhance the interaction of ledipasvir with HCV-infected hepatocytes through the development of cationic bilosomes (CBs) and galactosylated bilosomes (GBs). These delivery systems were designed to promote hepatocellular targeting via the asialoglycoprotein receptors (ASGPRs). Eight bilosomal formulations were developed by the ethanol injection method following a 2³ full factorial design, and numerical optimization using Design Expert^® software identified the optimized formulation. In parallel, galactosylated stearylamine (GSA) was synthesized through conjugation of stearylamine (SA) with lactobionic acid (LB). The successful synthesis of GSA was verified through FTIR and ¹H NMR spectroscopic analyses. SA and GSA were subsequently incorporated into the optimized bilosomes to obtain CBs and GBs, respectively. The prepared systems were evaluated for particle size, polydispersity index, entrapment efficiency, and zeta potential, and their morphology was identified using transmission electron microscopy. Following 8-h incubation with HepG2 cells, CBs and GBs achieved significantly higher cumulative cellular uptake of ledipasvir (31.79% ± 3.11% and 20.62% ± 2.12%, respectively) compared to the ledipasvir free dispersion (11.02% ± 3.02%). These findings highlight CBs and GBs as promising nanocarriers for targeted delivery of ledipasvir to hepatocytes.

Purpose: In order to develop reduction-responsive nano-drug delivery system for encapsulating antifungal drugs.

Methods: Herein, with poly (isobutene-alt-maleic anhydride) as skeleton, we synthesized a polymer containing cross-linked disulfide bonds to prepare reduction-responsive ketoconazole-loaded nanoparticles (MPEG-P-KET). The in vitro reduction-responsive behavior and antifungal activity of MPEG-P-KET were investigated.

Results: The MPEG-P-KET improved the dispersion and solubility of lipophilic KET. KET's imidazole group formed a salt with the free carboxyl groups in the polymer carrier, resulting in delayed drug release from MPEG-P-KET. However, MPEG-P-KET still exhibited reduction-sensitive drug release behavior, and showed comparable antifungal activity with KET in vitro. Interestingly, MPEG-P-KET demonstrated higher ability to inhibit biofilm formation and disrupt mature biofilms than KET.

Conclusion: The polymeric nanoparticles with disulfide bonds could be used for the encapsulation and controlled delivery of antifungal drugs in the field of fungal infection treatment.

Polymeric nanoparticles are promising drug carriers due to their biocompatibility, sustained release, and improved therapeutic efficacy; however, conventional fabrication methods often suffer from broad size distribution, low encapsulation efficiency, and instability. To address these limitations, Sonication Assisted Particle Production using Supercritical Solution (SAPSS®), a modified RESS technique integrating ultrasonication and mechanical mixing, was developed to prepare and optimize HPMC K-100M hydrogel nanoparticles encapsulating retinol acetate using DOE, RSM, and ANOVA. The optimized formulation (retinol acetate: HPMC K-100M, 1:1 w/w) produced at 290 bar and 75 °C for 45 min with 1% Tween 80 yielded nanoparticles of 138.6 ± 1 nm, PDI 0.583 ± 0.03, zeta potential -14.9 ± 2.0 mV, encapsulation efficiency 99.02 ± 0.2%, and yield 66.4 ± 0.3%. FTIR, DSC, and XRD confirmed amorphous encapsulation and drug-polymer interactions, while SEM demonstrated spherical, discrete morphology. In vitro release studies revealed sustained drug release across physiological pH, with mucoadhesive strength supporting gastrointestinal retention. Cytotoxicity assays on COLO-205 cells, doxorubicin showed >90% cytotoxicity, free retinol acetate caused only 10-25% cell death, while HPMC-encapsulated retinol acetate nanoparticles produced enhanced, dose-dependent cytotoxicity of 25%, 35%, and 55% at 100, 200, and 300 µg/mL, respectively, with negligible toxicity from blank HPMC. Overall, SAPSS® provides a green, scalable approach for fabricating stable therapeutic nanoparticles.

Background: The incidence of central nervous system (CNS) disorders is rising globally, particularly as the prevalence of neurodegenerative diseases increases. The primary challenge in such cases is limited transport of therapeutics through the blood-brain barrier (BBB). Statins, widely used for hypercholesterolemia, exhibit pleiotropic neuroprotective effects; however, their therapeutic potential in CNS disorders is restricted by poor brain bioavailability with conventional routes. Intranasal (IN) delivery has long been recognized as a plausible pathway for brain targeting.

Scope of the review: This narrative review critically examines preclinical literature on IN nanocarrier-based delivery systems developed specifically for statins, with emphasis on nose-to-brain transport, formulation strategies, pharmacokinetics (PK), and neuroprotective outcomes. Novelty and Contribution: This work uniquely integrates a formulation-centric comparison of IN nanocarriers for statins. It highlights the potential of IN delivery, discussing the influence of carrier type, physicochemical properties, and delivery strategy on brain targeting efficiency and therapeutic relevance across different neurological indications.

Conclusions and limitations: IN nanocarrier systems display potential to enhance statin brain delivery by bypassing the BBB and first-pass metabolism. Nevertheless, current evidence is predominantly preclinical, with significant variability in study design, pharmacokinetic reporting, and safety evaluation. Translation to clinics will require standardized nose-to-brain metrics, long-term safety studies, scalable manufacturing processes, and early regulatory alignment.

The therapeutic effectiveness of the most antihyperlipidemic drugs, particularly Biopharmaceutics Classification system Class II drugs like statins, is severely limited by their low aqueous solubility and resulting low and variable oral bioavailability (e.g. ∼5% for simvastatin). Deep Eutectic solvents and Therapeutic Deep Eutectic System are explored in this review as an environmentally friendly and innovative next-generation platform designed to overcome these fundamental biopharmaceutical limitations. These systems function as good solubilizers, improving the dissolution rate and the thermodynamic stability of antihyperlipidemic drugs significantly. This directly enhances the drug absorption kinetics, resulting in more predictable and enhanced oral bioavailability. Commercialization of DESs still faces major challenges. Large-scale-up is difficult because their high viscosity reduces mixing and mass transfer efficiency. Also, a complete evaluation of their cytotoxicity, biodegradability, and long-term thermal stability is still needed to ensure their safe and sustainable use as effective pharmaceutical excipients.

This study aimed to assess two parabens, methylparaben and propylparaben, as additives to study their effects on the ability of the eudragit S100 (EU) in stabilizing the supersaturation of dipyridamole (DP). Capability of EU/parabens binary compositions to stabilize DP supersaturation was compared with EU/parabens physical mixtures to recognize the influence of parabens on the EU-mediated DP supersaturation stabilization. The interaction between EU and parabens was studied by FT-IR studies. For EU/parabens binary compositions, the capability of EU in supersaturation stabilization of DP increased compared with the EU alone. When the EU was physically blended with parabens, DP supersaturation was not affected by the presence of parabens. This demonstrated that the impact of parabens on the supersaturation of DP could not be attributed to a higher stabilization influence on DP supersaturation exerted by the combination of the EU and parabens, but rather may be attributed to the enhancement effect of parabens on the dissolution rate of EU. FT-IR results demonstrated intermolecular interactions between EU and parabens which may contribute to enhancing the dissolution rate of EU. The recently revealed supersaturation improvement found in the present study is interesting and has the benefit of providing a higher drug supersaturation maintenance by polymers through the use of suitable additives.

This study optimized nintedanib dry powder for inhalation (DPI) and compared it with organic solvent-based spray drying and jet milling. A solid dispersion of nintedanib, polyvinyl alcohol (PVA), and leucine was produced by spray drying from an ammonium carbonate (Ab) aqueous solution. Formulation and process variables-API:(PVA+leucine (L)) mass ratio, PVA:L ratio, API: Ab ratio, total solids, and feed flow-were systematically screened to yield particles with geometric size ≤5 μm. Powders were characterized for morphology, moisture, density, particle size distribution, crystallinity, assay, and aerodynamic deposition. The optimized formulation showed good flowability and stability, with API content >80% in DPI particles; mass median aerodynamic diameter (MMAD) was 4.18 μm and fine particle fraction (FPF) 36.59%, indicating effective deep-lung delivery potential. Compared with conventional methods, the aqueous spray drying route delivered comparable or superior in vitro inhalation performance and delivery efficiency, while improving safety during the preparation and usage process (such as reducing the risk of organic solvent residue and dust exposure). These results provide a practical strategy for safe, efficient nintedanib inhalation formulations and a platform to spray dry other poorly water-soluble drugs into DPI particles.

Aim/background: Ensuring smooth and consistent vial flow on pharmaceutical filling line conveyors is essential for maintaining sterility, reducing downtime, and avoiding costly disruptions. However, irregular vial movement such as spacing gaps, clustering, and vial flipping is often seen, leading to filling delays, broken glass, machine stoppages, and extended batch times. Existing systems lack the ability to detect such irregularities in real time and provide actionable alerts.

Materials and methods: A lightweight, AI-guided framework was developed for detecting vial flow irregularities and classifying bottleneck risks using computer vision. A high-speed camera positioned above the conveyor captured video frames processed by YOLOv8 for real-time object detection. OpenCV was used to extract vial positions and calculate flow metrics (average spacing, standard deviation, inter-vial gap thresholds). A rule-based classification system assigned bottleneck risk levels: low, medium, or high. Operational conveyor footage from a pharmaceutical filling line was analyzed; to protect confidentiality, frames were de-identified and re-rendered as schematic visualizations that preserve vial geometry and spacing statistics.

Results: Across 15 operational frames, the classifier achieved an accuracy of 93.3%, F1-macro 95.21%. On throughput, the end-to-end pipeline processed frames at ∼18 FPS on CPU and ∼25 FPS on Jetson Nano. Detector evaluation yielded mAP@0.5 = 100.00%, mAP@[0.5:0.95] = 70.09%, precision = 98.65%, recall = 100.00%, F1 = 99.32% at confidence 0.50.

Conclusion: This scalable, non-invasive solution can be integrated into existing pharmaceutical lines to improve operational efficiency and product integrity. The rule-based approach offers interpretability, making it suitable for GMP-regulated environments. Across the operational validation set, the risk classifier achieved macro average precision of 95.24%, recall of 95.83%, and F1 of 95.21%.