Journal of Pharmaceutical Innovation最新文献

Purpose

The study of nanoparticles for antibacterial, antifungal, and anticancer action is an important sector in nanoscience. The use of plant extracts in nanoparticle synthesis is among the most simple, cost-effective, and ecologically acceptable strategies. The goal is to use Artocarpus altilis fruit extract to generate plant-mediated silver nanoparticles for its biological activity.

Methods

Phytochemical profiling of methanolic extract of Artocarpus altilis fruit was carried out. UV visible spectroscopy and scanning electron microscopy (SEM) are used to characterize the sample. The disc diffusion method was used to interpret antimicrobial activity. The MTT assay was used to determine the cytotoxicity.

Results

The presence of flavonoids, terpenoids, phenolic compounds, and others was discovered by phytochemical profiling. UV-visible spectroscopy was used to establish the existence of AgNPs, and a maximum absorbance range was obtained. The optimized nanoparticles were shown to have a spherical shape by the SEM pictures. Using the disc diffusion method, the defined AgNPs demonstrated antibacterial efficacy against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus at various doses, as well as antifungal efficacy against Aspergillus fumigates. When compared to doxorubicin, the lung cancer cell lines (A549 cell line) demonstrated potential anticancer activity of silver nanoparticles.

Conclusion

We discovered that silver nanoparticles made from Artocarpus altilis fruit extract have a similar effect to ciprofloxacin. The cytotoxic activity anticipated against the lung cancer cell line (A549 cell line) shows that the percentage of cell viability is identical to that of doxorubicin which indicates the potential for the treatment of lung tumors.

Purpose

The growing demand for effective pharmaceutical treatments, notably amidst health challenges like COVID, highlights the urgency for improved drug production techniques. This study examines the simulation of the Sulzer SMX static mixer in laminar conditions for the continuous pharmaceutical manufacturing of significant pharmaceuticals, notably imatinib.

Methods

Computational fluid dynamics (CFD) were employed to assess the SMX static mixer’s hydrodynamics and mixing performance. Emphasis was on mixing efficiency and residence time distributions (RTD) in a mixer with SMX elements. We refined the model’s reliability and explored the correlation between friction factor and Reynolds number. The Definitive Screening Design (DSD) was used to determine major factors impacting mixer dynamics.

Results

We established a novel correlation between friction factor and Reynolds number. The study reveal that lower flowrates significantly impact mixing efficiency, with different solvents inducing mixing delays. The RTD study identified the total inlet flowrate’s influence on distribution, with higher flowrates leading to more distinct RTD profiles and decreased axial mixing. The screening analysis highlighted flowrate’s dominance over other factors in determining mixing efficiency and residence time.

Conclusions

Through precise computational fluid dynamics (CFD) simulations, the study affirms the robustness of the developed model and underscores the novel correlation between the friction factor and Reynolds number. Insights into flow rate’s pivotal role in dictating mixer efficiency and residence time distribution are discerned, culminating in a comprehensive guide for refining static mixer operations for optimized drug manufacturing.

Purpose

Aceclofenac is a nonsteroidal anti-inflammatory drug (NSAID) belonging to BCS Class II, has a constraint over its therapeutic benefits owing to its poor aqueous solubility.

Methods

In this study, co-amorphous mixtures of Aceclofenac (ACE) with Aspartame (ASPA) of various molar ratios at specific milling times were produced through ball milling (BM) technique. The characterization was done using FTIR, DSC and PXRD. The pellets formulation was prepared by extrusion spheronization method using 3² full factorial design. The optimized formulation was evaluated for in-vitro and in-vivo performance.

Results

Amongst the co amorphous mixtures and pure ACE studied for solubility, ACE: ASPA (1:1) showed the significant increase in solubility and was further formulated as pellets. Solid-state characterization of mixture revealed amorphization of ACE after 120 min of ball milling. In-vitro dissolution study data of F4 pellets formulation revealed (99.00 ± 3.59%) significant increase (P < 0.005) compared to pure drug (50.12 ± 2.52%) and other formulations. The in-vivo studies reveal a significant increase in percent inhibition of inflammation (61.7%) of the prepared formulation (p < 0.05) as compared to the marketed formulation (53.19%), and pure drug (46.8%).

Conclusion

Therefore, the prepared pellets of co-amorphous mixture of aceclofenac and aspartame, boost the solubility and stability of aceclofenac which has a potential to be a promising approach in the management of pain.

Graphical Abstract

Purpose

The purpose of this study was to develop fluconazole microsponges loaded bioadhesive film, rolled into a torpedo-shaped capsule, to achieve ease of application and reduce application frequency for the treatment of vulvovaginal candidiasis. This was accomplished by using biodegradable polymer blend specifically designed to cater the busy lifestyle of working women.

Methods

Microsponges were prepared using the quasi-emulsion solvent diffusion method. Herein, fluconazole: ethyl cellulose (1:2.5, 1:3, 1:3.5) and polyvinyl alcohol (used as the external phase) were dissolved in dichloromethane (12.5, 15, 17.5 ml). Three-level, two-factor full-factorial design optimized the above process. Next, the developed microsponges were thoroughly evaluated for entrapment efficiency, drug release and antimicrobial study. Lastly, film was developed which was made up of blend of bioadhesive polymers, namely pectin and xanthan gum. Subsequently, film was rolled into a torpedo-shaped capsule shell.

Results

The spherical-shaped porous microsponges exhibited a notable entrapment efficiency (94.17%), size 14.68 μm and rapid drug release of 91.1 ± 1.54% within 10 h. Further, bioadhesive film revealed thickness 92 μm, folding endurance 440, moisture content 5.66 ± 0.51% w/w, and good tensile strength to withstand vaginal pressure and remarkable zone of inhibition against Candida albicans (19.1 mm).

Conclusion

Fluconazole microsponges loaded bioadhesive film, rolled into a torpedo-shaped capsule, exhibited an excellent aesthetic appearance. Moreover, strong bioadhesivity ensured a high efficacy in combating disease.

Introduction

High-shear wet granulation (HSWG) is most commonly used in the pharmaceutical industry, with the advantages of being fully enclosed, having a good mixing effect, and being highly efficient. However, only a few studies are geared toward an in-depth understanding of the pre-mixing process in the high-shear wet granulator (HSWGr).

Objectives

In this paper, the effect of impeller speed and fill level on the mixing performance of particles is investigated using the discrete element method (DEM), which provides theoretical references for the energy-saving operation in HSWGr.

Methods

Relative standard deviation (RSD) was used as a mixing index to quantify mixing quality, particle temperature over a vertical distance to quantify particle motion bias, and total power consumption per unit mass to monitor the loss effect.

Results

The simulation results show that the impeller speed only affects the mixing process and does not change the mixing uniformity; the fill level has a significant effect on the particle mixing, and a higher fill level will inhibit the particle mixing; based on the uniform mixing, the fill level has little effect on the total power consumption per unit mass.

Conclusion

The results of the study show that increasing the fill level and impeller speed contributes to the energy-saving operation of HSWGr.

Purpose

This work seeks to improve the particle processability of needle-like lovastatin crystals and develop a small-footprint continuous MicroFactory for its production.

Methods

General conditions for optimal spherical agglomeration of lovastatin crystals and subsequent product isolation are developed, first as batch processes, and then transferred to continuous MicroFactory operation.

Results

Methyl isobutyl ketone is a suitable bridging liquid for the spherical agglomeration of lovastatin. Practical challenges including coupling unit operations and solvent systems; mismatched flow rates and inconsistent suspension solid loading were resolved. The successful continuous production of lovastatin spherical agglomerates (D₅₀ = 336 µm) was achieved. Spherical agglomeration increased the density of the bulk lovastatin powder and improved product flowability from poor to good, whilst maintaining lovastatin tablet performance.

Conclusion

A continuous, integrated MicroFactory for the crystallisation, spherical agglomeration, and filtration of lovastatin is presented with improved product particle processability. Up to 16,800 doses of lovastatin (60 mg) can be produced per day using a footprint of 23 m².

Purpose

Silicone oil droplets in biopharmaceutical products can originate from sources such as siliconized surfaces of primary packaging materials, potentially triggering the formation of protein–silicone oil particles. To better understand this phenomenon, there is a need for particle detection devices that cannot only distinguish between protein particles and silicone oil droplets but also determine particle sizes ranging from nanometers to micrometers.

Method

In this study, we conducted a systematic assessment of imaging flow cytometry (IFC) using the FlowSight® instrument. Our first step was to investigate specific instrument settings using protein particle samples spiked with silicone oil for particle classification. Based on these findings, we established suitable, harmonized working templates. Next, we evaluated the instrument’s accuracy and precision for particle sizes within the range of 0.5 to 100 µm and their respective concentrations. Finally, we investigated any constraints in particle concentration within this size range.

Results

This study demonstrates that IFC can effectively distinguish protein particles from silicone oil droplets when the latter is labeled with a specific fluorescent dye. Our findings suggest that fluorescently labeled particles ≥ 0.5 µm can be reliably detected. Through our research, we determined the particle concentration limits for each particle size in the range of 0.5 to 10 µm, with a precision deviation of less than 15%. However, our study also revealed that IFC exhibited insufficient accuracy for the tested particle concentrations within this size range. Additionally, we showed that the measurements were significantly influenced by the instrument settings.

Conclusion

Although we addressed numerous new aspects to enhance the experimental procedure of IFC measurements, we conclude that IFC is not an ideal technique for quantifying sub-visible particles. Instead, it should be employed to provide supportive characterization data in conjunction with commonly used sub-visible particle detection methods. If distinguishing between protein particles and silicone oil droplets is essential, IFC is an option, as long as the fluorescent dye is carefully selected.

Graphical Abstract

Background

Isoformononetin (IFN) is a methoxyl derivative of daidzein and has been stated as a potent osteogenic isoflavone. However, IFN has low oral bioavailability. Advancement in the technology has led to the development of newer drug carrier systems, featuring the delivery of drugs with low oral bioavailability to advance their clinical application.

Methods

The IFN nanoemulsion (IFN-NE) was developed and optimized using the design of the experiment tool and technique approaches.

Results

The optimized IFN-NE has a particle size of 174.65 ± 1.63 nm, PDI of 0.244 ± 0.004, and zeta potential of − 30.69 ± 4.99 mV, respectively. The TEM images of optimized IFN-NE showed the spherical globular size of the nanoemulsion. The entrapment efficiency showed higher entrapment of IFN in the NE (96.04 ± 1.28%). The compatibility of IFN with excipients was confirmed by physical state characterization such as FTIR and DSC, illustrating no interaction. Optimized IFN-NE formulation was stable at different temperature conditions. In comparison to a free drug suspension, IFN-NE showed sustained drug release over a 24-h period of time. Additionally, in situ, single-pass intestinal perfusion (SPIP) results displayed significant enhancement of IFN permeability through the intestine of rats from IFN-NE when compared to free IFN.

Conclusions

Pharmacokinetics results revealed the enhanced relative oral bioavailability of IFN-NE compared to IFN suspension using female Sprague–Dawley (SD) rats as animal models. The developed IFN-NE can be a promising candidate to overcome the low oral bioavailability of IFN.

Graphical Abstract

Drug repurposing has emerged as an enigmatic clinical approach in disorders affecting the cardiovascular system. The concept of drug repurposing has become feasible due to an interim in performing trials for new entities in cardiovascular diseases (CVDs) rather than cancer and diabetes. One of the naïve pathologies brought to the forefront was IL-33/ST2. After delving deeply into this pathway, mitigated levels of sST2 (a decoy receptor for IL-33) were found to prevent plaque formation and fibrosis. This novelty demands the identification of novel therapeutic targets. In this study, the chronopharmacology of frequently prescribed conventional cardiovascular medications was evaluated, and a hypothesis on β-blockers and mineralocorticoid receptor antagonists in modulating the IL-33/ST2 pathway was proposed for their ability to upregulate IL-33, which specifically exhibits cardioprotective activity. This future perspective advocates precise influences in aiming for IL-33 as a key factor for repurposing these medications in CVDs that reduce inflammation and help to unravel potential cardioprotective action and promising outcomes.

Purpose

Amoxicillin, a treatment option widely employed against H. pylori infection, is becoming ineffective due to the rising antimicrobial resistance. The poor stability of amoxicillin in gastric juice, as well as amoxicillin resistance in H. pylori, has a negative impact on amoxicillin’s therapeutic efficacy. Because of its metal chelating capacity, phytic acid has been shown to improve the antibacterial effectiveness of adjunct antimicrobials. Gastroretentive drug delivery carriers present a viable approach for treating gastric conditions owing to their higher gastric residence time and controlled drug release properties.

Methods

In the current investigation, amoxicillin and phytic acid loaded benzalkonium chloride (BAC) cross-linked pectin microparticles were prepared via ionic gelation technique with 83.65 ± 3.12% yield. Microparticles were evaluated based on drug release profile, drug degradation, permeation, mucoadhesion, β-lactamase inhibition, in vitro antimicrobial activity, in vivo gastro retention, in vivo gastroprotection and in vitro cytotoxicity parameters to ensure their therapeutic outcomes.

Results

In silico investigation predicted higher binding affinity (− 5.752 kcal/mol) of phytic acid with β-lactamase enzyme than clavulanic acid (− 4.870 kcal/mol). The microparticles that demonstrated 85.21 ± 1.12% entrapment efficiency and good mucoadhesive profile (~ 40%) showed high gastric stability and sustained release profile (~ 82% release in 14 h). SEM examination portrayed non-spherical particles with porous surfaces. FTIR and DSC analyses revealed no interaction between the drug and the polymer matrix. Microparticles were found to have superior β-lactamase inhibition potential and higher zone of inhibition (27.66 ± 2.49 mm)) compared with pure drug (18.33 ± 1.69). X-ray radiography study indicated that the prepared microparticles retained in the stomach for over 4 h.

Conclusion

In conclusion, provided with tremendous improvement in the drug’s stability in the gastric environment, these microparticles pose a viable option in the treatment of H. pylori infections.

Graphical Abstract