Journal of Pharmaceutical Innovation最新文献

Osteoarthritis (OA), a debilitating degenerative joint disease characterized by progressive cartilage degradation, chronic inflammation, and oxidative stress, necessitates innovative therapeutic interventions. This study aimed to develop and evaluate a transdermal delivery system comprising Ibudilast, a novel PDE4 inhibitor, to establish its effectiveness in the management of osteoarthritis. Ibudilast-BSA nanoparticles were prepared by desolvation and then incorporated into Carbopol 980 gel to form a nanogel formulation. Both the nanoparticles and the nanogel were evaluated by in vitro release, ex vivo permeation, and other parameters. The therapeutic efficacy of the nanogel batch was assessed in monosodium iodoacetate (MIA)-induced osteoarthritic rats using biochemical analysis, hematological assessment, radiographic examination, and histopathological evaluation. The developed nanoparticles had a uniform size of about 270.4 nm, a zeta potential of − 23.3 mV, and a drug encapsulation efficiency of 69.11%. The nanogel showed a skin-friendly pH (6.0), suitable viscosity, good spreadability, and sustained drug release (87.6% in 24 h). Ex vivo tests confirmed higher skin penetration (78.6%) compared to plain drug (24.3%). The topical PDE4 inhibitor nanogel showed significant therapeutic efficacy compared with the plain dispersion in MIA-induced OA rats, underscoring its therapeutic promise. The Ibudilast-loaded nanogel significantly reduced oxidative stress and inflammatory biomarkers while improving antioxidant levels and cartilage integrity in osteoarthritic rats. The Ibudilast-loaded BSA nanoparticle-incorporated Carbopol nanogel demonstrated therapeutic promise as an effective transdermal strategy for managing osteoarthritis. These findings deserve further investigation in chronic models and clinical settings to validate the translational potential of this novel formulation.

Liver cancer (LC) is the fourth most prevalent cause of cancer-related death worldwide. However, existing treatment options have limitations, as they do not consistently provide benefits to all patients. With an emphasis on pyrimidine derivatives, this study uses virtual screening approaches to find possible therapeutic agents against LC. These techniques include ADMET prediction, molecular docking, molecular dynamics (MD) simulations, density functional theory (DFT), and network pharmacology analysis. Fifteen compounds (1, 4, 6, 9, 16, 18, 27, 33, 38, 39, 40, 43, 44, 49, and 50) were selected for molecular docking studies against the EGFR kinase mutant T790M/L858R (PDB ID: 3W2Q) based on their favorable drug-like properties as determined by ADMET analysis. Compound 9 had the best Prime MM/GBSA score of -51.55 kcal/mol and the strongest binding affinity of -7.9 kcal/mol among the compounds that were chosen. It formed several hydrogen bonds with significant residues, including Lys745, Thr854, Met793, and Gln791, in the active site of the EGFR kinase mutant T790M/L858R. These interactions were superior to those of the reference compound (Erlotinib), which had a binding affinity of -6.4 kcal/mol and an MM/GBSA score of -52.51 kcal/mol. The enhanced stability of compound-9 over Erlotinib and the apo protein was also confirmed by molecular dynamics (MD) simulations, as evidenced by significant parameters such as RMSD, RMSF, radius of gyration (RoG), hydrogen bond interactions, principal component analysis (PCA), dynamic cross-correlation matrix (DCCM), and free energy landscape (FEL) analysis. Furthermore, the binding free energy of compound-9 was − 39.62 kcal/mol, while that of Erlotinib was − 42.13 kcal/mol. Network pharmacology research identified EGFR as a key target in the development of liver cancer (LC), since Gene Ontology (GO) and KEGG enrichment studies indicate that compound-9 may exert its inhibitory effects through several pathways, including the EGFR kinase pathway. These findings highlight the potential of compound-9 as a drug to treat LC.

Background

An important risk factor for cardiovascular illnesses, hyperlipidaemia is defined by increased lipid levels and frequently need long-term medication. Because of its limited water solubility and substantial first-pass metabolism, rosuvastatin calcium, a powerful lipid-lowering medication, has a low oral bioavailability (~ 20%).

Objective

In order to increase the bioavailability and sustained release of rosuvastatin calcium, this study set out to create and assess a liposomal mucoadhesive buccal film.

Methods and Results

Thin film hydration was used to make the liposomes, and Box-Behnken Design (BBD) was used to optimize them. The sonication time, cholesterol content, and lipid concentration were all considered independent variables. The improved formulation showed an entrapment effectiveness of 84.42%, a zeta potential of -24.73 mV, and a vesicle size of 164.3 nm. Through solvent casting, the liposomes were integrated into mucoadhesive buccal films using HPMC K4M and HPMC E5. The films were assessed for their physical characteristics, drug content, mucoadhesive strength, swelling index, and in vitro and ex vivo drug release. Superior properties, such as 80.23% in vitro drug release and 80.96% ex vivo permeation over 24 h, were shown by formulation F1 (containing HPMC K4M), which followed Higuchi kinetics. Under expedited settings, stability experiments verified constant medication release and film integrity after three months.

Conclusion

The liposomal buccal film exhibited sustained In vitro drug release, indicating its potential as a patient-friendly formulation approach for the effective delivery of rosuvastatin calcium in hyperlipidaemia.

Artemether (AE), which is a highly active antimalarial possessing newly found neuro‑protective potential, suffers from low aqueous solubility, high first‑pass metabolism, and minimal blood–brain‑barrier (BBB) penetration. The research aimed at developing an in-situ gel with AE-loaded solid lipid nanoparticles (SLNs) and optimizing it employing a 3² complete factorial design. Glyceryl monostearate (GMS)‑based SLNs were prepared by high‑pressure homogenization (HPH) (356.9 ± 2.3 nm; PDI 0.442; ζ‑potential − 16.7 mV; entrapment efficiency 86.5 ± 1.5%). Lyophilized nanoparticles retained spherical shape, structural integrity, and a shifted DSC endotherm at 62.2 °C, establishing molecular dispersion of AE. In situ gels were developed using gellan gum (0.30–0.50% w/v) and Carbopol 934P (0.05–0.25% w/v). Design‑Expert^® revealed an optimum formulation composition of 0.36% gellan gum + 0.14% Carbopol, providing viscosity 548 ± 12 CP, mucoadhesive strength 701 ± 17 dyne cm⁻², and 93.0 ± 1.1% cumulative release in 6 h. Release kinetics obeyed the Higuchi model (R² 0.981) with a Korsmeyer–Peppas exponent 1.08, demonstrating super‑case‑II transport regulated through diffusion and polymer relaxation. Ex vivo permeation through goat nasal mucosa reflected an 8.3‑fold increase in flux compared to plain AE, while a one‑month accelerated‑stability study validated physicochemical stability. Together, these results show that an ion-activated, SLN-loaded gellan–Carbopol matrix can release AE in a sustained form and significantly increase nose-to-brain permeation, presenting an appealing platform for both antimalarial and neuro-therapeutic uses.

Regioselective elaboration of a 4-bromobenzyl-1H-1,2,3-triazole scaffold was achieved through a concise, metal-free sequence that preserves the C-4 carboxylate as a metal-coordinating handle while diversifying the C-5 position. Thermal azide–alkyne cycloaddition between 1-(azidomethyl)-4-bromobenzene and dimethyl but-2-ynedioate furnished the 4,5-diester core, followed by LTBA-mediated, chemoselective reduction of the C-5 ester to an aldehyde at − 10 °C in THF. Modular condensation of the aldehyde delivered three derivatives—Schiff base (a2), hydrazone (a3), and benzimidazole (a1)—in 95–98% yields, with structures confirmed by NMR and HRMS. The regioselective design maximized metal coordination (Ni²⁺, Zn²⁺, Fe³⁺) and produced multi-target inhibition against urease, collagenase, and 15-LOX; the imine derivative a2 was most potent (IC₅₀: 7.21 µM, 27.36 µM, 2.76 µM, respectively), consistent with docking, MD, and MM/GBSA analyses. This synthesis-first strategy establishes a privileged, polypharmacological platform for gastric-injury targets.

Graphical Abstract

Purpose

Vonoprazan fumarate (VPF) is a novel potassium-competitive acid blocker with promising therapeutic potential for acid related disorders and as an adjunct to Helicobacter pylori eradication, yet its clinical utility is limited by poor solubility and low bioavailability. Here, we explore the development of amorphous solid dispersion (ASD)-loaded orodispersible films (ODFs) to overcome these barriers.

Methods

ASDs of VPF were prepared and characterized using hydroxypropyl methylcellulose (HPMC K4M), polyethylene glycol 4000, and Poloxamer 407. ODFs were fabricated by solvent-casting with sodium carboxymethyl cellulose, HPMC K4M, and polyvinyl alcohol (PVA) as film-forming polymers, incorporating glycerin as a plasticizer. Various parameters as weight and thickness variation, in-vitro drug release, disintegration time, moisture uptake, and in-vivo pharmacokinetic parameters were investigated.

Results

VPF ASDs were achieved the optimal dissolution at a 1:6 (w/w) drug-to-polymer (HPMC K4M) ratio with Higuchi-diffusion kinetics. Stability studies confirmed VPF integrity in the ASD form. Among the ODF formulations, ODF7 (contains 75 mg PVA) demonstrated superior performance with rapid disintegration, lowest moisture uptake, and maximum drug release within 10 min. In-vivo pharmacokinetic evaluation in rabbits revealed a 2.2-fold increase in relative bioavailability (221.98%) compared to the VPF marketed tablet, while palatability testing confirmed its acceptability.

Conclusion

These findings demonstrate the potential of VPF-ASD-loaded ODFs as a viable approach to enhance drug solubility, stability, and systemic exposure.

Purpose

Cyclodextrins (CDs) are cyclic oligosaccharides widely employed in pharmaceutical formulations due to their unique ability to form inclusion complexes with a broad range of drugs thus improving their solubility and bioavailability. In recent years, chemical modification of CDs has emerged as a powerful strategy to enhance their drug delivery capabilities. This review provides a focused overview of chemically modified CDs developed in the last 15 years (2010–2025) with the aim of improving solubility, drug encapsulation efficiency, and delivery.

Methods

Particular attention is given to the synthetic strategies employed to obtain functionalized CDs capable of providing enhanced biopharmaceutical properties such as improved drug solubility, receptor binding features, drug retention and permeation on absorption sites.

Conclusions

Tailored chemical modifications have been reported to improve the pharmacokinetics, bioavailability, and controlled release of encapsulated drugs, thereby helping to address some limitations of native CDs and potentially supporting the development of advanced drug delivery systems with improved selectivity and reduced side effects. Progress in this field underscores the importance of molecular design in the development of next-generation pharmaceutical excipients.

Purpose

This study introduces an innovative mixed-mode high-performance liquid chromatography (HPLC) method employing a Hi-Plex H column that synergistically combines size exclusion and ion exchange mechanisms, enabling precise and reproducible quantification of PVP K30 in diverse matrices, including pharmaceutical, cosmetic, and environmental water.

Methods

This study introduces an innovative mixed-mode high-performance liquid chromatography (HPLC) method employing a Hi-Plex H column using an isocratic 1:1 mix of 70% perchloric acid (pH ~1.5) and acetonitrile at 1.5 mL/min flow, 25°C, with detection at 210 nm and a 12-minute run time. A solid phase extraction pretreatment method was used to enhance their detection in wastewater. The method’s environmental impact was rigorously audited using established greenness metrics (AGREE, AGREEprep, MoGAPI, BAGI, and RGB12), providing a transparent assessment of its sustainability profile.

Results

The validated method demonstrated excellent linearity (4-500 μg/mL; r²= 0.9997) with limits of detection and quantification of 1.2 μg/mL and 3.8 μg/mL, respectively. Implementation of an optimized SPE protocol, providing a 500-fold preconcentration, enabled exceptional environmental sensitivity (LOD: 2.4 ng/L in the original water sample). High accuracy was achieved with recovery rates of 98.35-99.45% in commercial products and 82.02-85.10% in water samples. A comprehensive evaluation using AGREE, AGREEprep, MoGAPI, BAGI, and RGB12 tools provided a multi-faceted perspective on the method's practicality and environmental footprint, with a high practical applicability score (BAGI = 70.0) and an overall whiteness score of 72.0.

Conclusion

The developed method represents a significant advancement in polymer analysis, providing a sensitive and versatile solution for PVP K30 monitoring in both industrial quality control and environmental protection applications. The integrated greenness assessment provides a benchmark for the environmental impact of this analysis and identifies areas for future improvement. 

Graphical Abstract

Highlights