Pharmaceutical Development and Technology最新文献

Clobetasol propionate (CP) is a potent Class I corticosteroid widely used to treat dermatological conditions; however, its poor aqueous solubility limits bioavailability. In this study, a nanostructured lipid carrier (NLC)-based gel was developed via the microemulsion method to improve the topical delivery of CP. The formulation was optimized using stearic acid (solid lipid), Captex 300 (liquid lipid), Tween 20 and Span 80 (surfactants), and propylene glycol (co-surfactant), based on solubility and thermodynamic stability assessments. Vitamin E acetate was incorporated as an antioxidant to inhibit lipid oxidation and enhance formulation stability. The optimized CP-NLC (F5) formulation had a particle size of 75.96 ± 4.87 nm, a zeta potential of -23.88 ± 4.10 mV, and a polydispersity index (PDI) of 0.27 ± 0.11. Encapsulation efficiency was 93.72 ± 0.26%, and drug loading reached 100.69 ± 0.62%. Transmission electron microscopy (TEM) confirmed spherical morphology. The gel (CP-NLC-F5-G) prepared with Carbopol 934 demonstrated a pH of 5.58 ± 0.68 and drug content uniformity of 99.03 ± 1.18%. In vitro release studies using Franz diffusion cells revealed sustained CP release compared to a commercial product. Stability studies indicated long-term encapsulation retention, attributed to the antioxidant effect of Vitamin E acetate. These findings suggest the potential of CP-NLC systems for effective, sustained corticosteroid delivery with enhanced dermal retention.

Felodipine is traditionally delivered as extended-release tablets, but a push-pull osmotic pump (PPOP) capsule represents a promising alternative platform for controlled-release delivery. This work sought to characterize properties of the felodipine drug substance and crosslinked hard gelatin capsules (HGCs) for the preparation of the PPOP capsule. Additionally, drug release profiles of felodipine PPOP capsules under various formulation and medium conditions were investigated. Felodipine drug substances and crosslinked HGCs were evaluated for their physicochemical properties. Moreover, the type of release medium, number of Corelease CA coating rounds, amounts of Polyox WSR N80 and Polyox WSR Coagulant, sodium chloride content, and source of the drug substance were studied. Results showed that the physicochemical properties of felodipine drug substances exhibited statistically significant but minor variations between the two sources. Crosslinked HGCs remained insoluble in all tested media and exhibited spectral changes consistent with formaldehyde-induced crosslinking. Drug release approached Higuchi's kinetics when the formulation comprised 10 mg felodipine from a specific manufacturer, 120 mg of Polyox WSR N80, 35 mg of Polyox WSR Coagulant, and 20 mg of sodium chloride, with 10 coating rounds of Corelease CA and 1% sodium lauryl sulfate as the release medium. In conclusion, these findings highlight the significant influence of formulation parameters on drug-release behavior and provide a basis for developing PPOP capsules with consistent and predictable performance.

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.

The present paper provides a detailed overview of surfactants' function in HIV/AIDS therapy, with a focus on medication administration, direct antiviral mechanisms, and microbicide formulations. The use of surfactant-based nanotechnology into antiretroviral therapy has resulted in the development of liposomes, polymeric micelles, nanoemulsions, and surfactant-modified biomaterials that provide controlled release and increased bioavailability of antiretrovirals. Furthermore, many surfactants have inherent antiviral activity, which disrupts the viral lipid envelope, inhibits viral replication, and prevents HIV from entering host cells. The paper also explores the potential of surfactant-based biosensors for HIV diagnostics, emphasizing their role in improving sensitivity and selectivity and recent progress in formulation design using surfactants such as sodium lauryl sulfate, poloxamers, and biosurfactants, emphasizing their safety, biocompatibility, and clinical potential. Key challenges including scalability, environmental impact, and user acceptability are discussed alongside emerging AI-driven approaches for personalized nanomedicine. Surfactant toxicity and limited biocompatibility remain key barriers. Developing safer, more effective surfactants is essential for future clinical progress.

Baicalin is a flavonoid glycoside with substantial biological activity and pharmacological effects, primarily extracted from Scutellaria baicalensis Georgi. However, its clinical implementation has been impeded by suboptimal aqueous solubility and unfavorable bioavailability. This study employed a supercritical anti-solvent (SAS) process to prepare amorphous solid dispersions of baicalin, aiming to enhance its dissolution and bioavailability. The effects of supercritical temperature, supercritical pressure, and CO₂ flow rate on encapsulation were thoroughly investigated using the Box-Behnken Design (BBD) response surface methodology. SEM, FTIR, DSC, and XRD analyses confirmed that the baicalin solid dispersion prepared via the SAS method was in an amorphous state. In vitro dissolution tests indicated that the solubility of baicalin in the solid dispersion was 9.4 times (pH = 6.8) greater than that of the raw baicalin particles. Furthermore, rat experiments revealed that the bioavailability of baicalin in the solid dispersions was 1.8 times higher than that in traditional particles. Notably, BASD exhibited strong inhibitory effects on the growth of Bacillus subtilis and Escherichia coli. Consequently, a solid dispersion of baicalin was successfully prepared using the BBD-optimized SAS process, significantly enhancing the performance of baicalin.

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.