Journal of Pharmaceutical Innovation最新文献

Background

Traditional routes of administration of fluconazole such as eye drops have a low therapeutic efficacy due to insufficient bioavailability.

Purpose

Herein, a fluconazole noisome-laden contact lens was prepared to control and prolong the drug release and improve its bioavailability.

Methods

Two methods have been used to prepare fluconazole niosomes: solvent injection method and thin film hydration method utilizing span 60 and cholesterol mixture. Subsequently, formulations were optimized using three factors and a two-level factorial design and were subjected to in-vitro characterization for the size of niosomes, zeta potential, entrapment efficiency percent, and cytotoxicity study. The optimized fluconazole niosomes were further entrapped in contact lenses by the soaking method and were evaluated according to in-vitro release profile, and antimicrobial activity.

Results

The results revealed that the investigated fluconazole niosomes are of nano-size ranging from 228.2 to 769.2 nm with zeta-potential values between − 18.1 and − 60.2 mV. The entrapment efficiency percentage ranged from 51.3 to 75%. Fluconazole was released from fluconazole noisome-laden contact lens and showed a prolonged release up to 48–72 h with a cumulative release of 79.62%. Statistical analysis showed that fluconazole-noisome-laden contact lenses have a significant impressive fungal adhesion reduction as compared to fluconazole-laden contact lenses.

Conclusion

Fluconazole noisome-laden contact lenses are a promising therapeutic way for effective and prolonged treatment of ocular fungal infection.

Purpose

To improve azithromycin’s antibacterial activity at different pH through combination therapy.

Method

Azithromycin- and ibuprofen-loaded micelles were fabricated by the self-assembly of MPEG-PVL copolymer, respectively.

Results

The drug-loaded micelles had controlled drug release property with water-solubility improvement. Notably, at pH 7.4 or 6.0, the in vitro antibacterial experiments demonstrated that there was no synergistic effect for the two native drugs against S. aureus, but a significant synergy was observed when the two preparations were used in combination. In vitro PI fluorescence staining experiment demonstrated that the introduction of ibuprofen-loaded micelles obviously increased cellular uptake under low concentration of azithromycin-loaded micelles. Through SEM and spectral evaluation experiments, it was found that ibuprofen-loaded micelles could increase the cell permeability by interacting with proteins and phospholipids in the cell membrane, which was conducive to promoting azithromycin-loaded micelles to enter the cells and play a drug effect.

Conclusion

The azithromycin- and ibuprofen-loaded micelles with synergistically enhanced antibacterial activity are potential candidates for effective bacterial combination therapy.

Graphical Abstract

This study focused on the preparation and characterization of rilpivirine-loaded nanobilosomes. Formulations were developed using rilpivirine, phosphatidylcholine S-100 (SPC), and sodium deoxycholate (SDC) via the thin film hydration method. The nanobilosomes were characterized for vesicle size, polydispersity index (PDI), surface charge, and entrapment efficiency (%EE). Thermal behavior and drug-excipient interactions were analyzed using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Transmission electron microscopy (TEM) revealed that BS-06 nanobilosomes possess a smooth and uniform surface morphology. In vitro cytotoxicity assays were conducted on HeLa and HEK 293 cell lines, and minimum inhibitory concentration (MIC) was assessed against S. aureus and E. coli. Stability was monitored over 3 months at various temperatures. The optimized formulation (BS-06) exhibited a vesicle size of 132.8 ± 4.0 nm, a zeta potential of -30.10 ± 0.8 mV, and a PDI of 0.20, demonstrating optimal surface characteristics and maximum entrapment efficiency. In vitro release studies indicated a maximum drug release of 84.81 ± 4.6% over 24 h. Cytotoxicity studies showed that BS-06 improved cell viability in HeLa and HEK 293 cell lines at 24 and 48 h and enhanced antibacterial activity against S. aureus and E. coli. Overall, our findings highlight the potential of rilpivirine-loaded nanobilosomes as a promising drug delivery system for HIV/AIDS, with enhanced dissolution, stability and biocompatibility.

Purpose

The manufacturing industry is changing quickly because of trends like automation and high-volume customization. Industry 4.0 is a movement towards digitization that incorporates cutting-edge technologies to improve consumer experiences and provide better control over production operations. The primary objective of this study is to identify and prioritize the significant obstacles hindering the implementation of Industry 4.0 technologies within the Indian pharmaceutical sector.

Methods

A multi-methodological approach was taken, consisting of the following steps: (1) creating a keyword string based on the PICO framework to collect pertinent literature; (2) using the Delphi technique to interview industry experts; and (3) using the Analytical Hierarchy Process (AHP) to rank challenges by significance.

Result

The study identified and ranked fifteen critical obstacles that Indian pharmaceutical companies must overcome to implement Industry 4.0. The analysis revealed that ‘lack of awareness’ is the most significant barrier.

Conclusion

Promoting awareness through focused education and industry engagement is crucial to realizing the impending of Industry 4.0.

Introduction

This current research reports the synthesis and characterization of a cocrystal of Fluconazole (FLU), a widely used antifungal drug, with a nutraceutical coformer (NCF) that has potential health benefits as well as improving its solubility and antifungal activity.

Method

The co-crystal was obtained by solvent evaporation in a stoichiometric ratio using three natural coformers: Ferulic acid, caffeic acid, and glycerine, and characterized by various analytical techniques, including Powder x-ray diffraction (PXRD), Differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy.

Results

The cocrystals showed lower heats of fusion (ΔH) compared to pure Fluconazole, indicating the possibility of increased entropy and solubility for all cocrystals. Using the solvent evaporation method with ferulic acid, caffeic acid, and glycine showed significant enhancement of solubility, ranging from 1.06-fold to 4.80-fold, depending on the co-former and different media used.

Discussion and Conclusion

The zone of inhibition assay showed that cocrystals of Fluconazole with nutraceuticals (FLU+CAF, FLU+GLY, and FLU+FER) exhibited higher zones of inhibition compared to pure Fluconazole and DMSO control. Solubility and dissolution studies revealed that cocrystals of Fluconazole with nutraceutical coformers could be an effective approach to enhancing the solubility and antifungal activity of Fluconazole.

Graphical Abstract

Purpose

The primary aim of this study is to develop a cubosome nanoformulation for the optimized delivery of nimesulide, with a focus on improving its efficacy and reducing adverse effects. The ultimate goal is to advance the pharmaceutical application of nimesulide by achieving sustained release kinetics.

Method

A systematic approach was employed to develop nine cubosomal formulations using a top-down strategy with the primary focus on optimizing the lipid (glyceryl monooleate - GMO: X₁) and surfactant (Pluronic F-127 - PF-127: X₂) concentrations. The selection of these variables was based on a 3²-factorial design. The impact of varying concentrations of GMO and PF-127 on critical parameters such as particle size distribution and entrapment efficiency were thoroughly investigated.

Results

The optimized formulation demonstrated favorable characteristics, including a particle size ranging from 153.5 ± 4.99 to 199.6 ± 10.23 nm, and EE between 70.5 ± 1.85 to 88 ± 2.17%. Zeta potential values ranged from − 35.6 to -40.5 mV, while PDI values fell within the range of 0.32 to 0.51. In vitro investigations revealed a meticulously sustained drug release profile with regulated kinetics observed over a 24 h period. Rheological studies provided insights into the viscoelastic behaviour and structural integrity of the cubosomal gel formulation. Ex vivo absorption studies conducted on goat skin demonstrated superior drug absorption and sustained release patterns compared to a commercially available gel.

Conclusions

The study concludes that the application of nimesulide-loaded cubosomal gel has the potential to enhance drug absorption and facilitate sustained release. This nanoformulation presents a promising strategy for improving the topical delivery of nimesulide while minimizing adverse effects.

The expansion of spectroscopic process analytical technology (PAT) within the pharmaceutical industry requires chemometric models to enable spectral interpretation. However, calibration of chemometric models often require an intense time, material, and financial burden which may discourage PAT deployment. The advancement of modeling strategies that reduce this calibration burden necessitates consistent terminology for describing model inputs and overall calibration burden throughout chemometric literature. The goal of this article is to define levels of calibration burden by clarifying dataset classifications and model inputs during PAT method development. The scope of this work is specific to calibration of chemometric models incorporated in PAT methods. Harmonizing the language used in the field of chemometrics to describe calibration burden benefits both pharmaceutical manufacturers and regulatory agencies.

Purpose

Decitabine is an inhibitor of DNA methyltransferase used to treat various types of leukemias. However, it is highly unstable in nature thereby needing an innovative intervention to harness its benefits. Thus, the study aimed to develop a stable nano-formulation of decitabine with improved pharmacokinetic characteristics.

Method

In the present study, the Quality by Design approach was employed to systematically design and optimize decitabine-loaded nanoparticles. The nanoparticles were fabricated with emulsion solvent diffusion method and screened by 2^K-1 fractional factorial design followed by Box-Behnken design to obtain nanoparticles with desirable characteristics. The optimized uncoated formulation was surface-modified to obtain PEGylated nanoparticles. The developed nanoparticles were further lyophilized using a suitable lyophilization cycle to obtain highly stable decitabine-loaded nanoparticles. The developed nanoformulations were assessed with in vitro and in vivo evaluation.

Result

The lyophilized decitabine-loaded, uncoated and PEGylated nanoparticles exhibited a particle size of 194.5 nm and 177.9 nm and zeta potential of -32.9 mV and − 31.0 mV, respectively. Also, these exhibited a desirable encapsulation efficiency of 85.2% and 90.9%, respectively. The developed nanoformulations indicated a prolonged drug release over a period of 7 h. The in vivo study confirmed the improved pharmacokinetic parameters for drug-loaded nanoparticles in comparison to drug solution.

Conclusion

The drug-loaded lyophilized nanoparticles were successfully developed and showcased superior quality attributes in both in vitro and in vivo assessments. This study thereby underscores the possible application of this nano-therapeutic system for leukemia treatment with implications for the broader landscape of nanomedicine and precision technology.

Purpose

Although pharmaceutical high-speed filling lines are fully automated, interventions are still performed by hand via glove ports. Bringing robots into the high-speed production lines for the handling of interventions could increase both the thoughput and the sterility of the system. The work presented in this manuscript proposes a semi-autonomous intervention strategy for the removal of erroneous plungers.

Methods

A YOLOv8-based computer vision algorithm continuously monitors the state of the plunger feed. Autonomous motion planning is used for large, general movements, while human-operated teleoperation with system guidance allows for small, precise motions. The combination of both creates a intuitive, gloveless intervention method.

Results

A user test with a group of 22 volunteers shows that an untrained operator can perform the teleoperated intervention via this system in an average of (pm 30)s and (pm 21)s when the plungers are static and dynamic respectively. Via a Likert-scale based questionnaire, it was found that the test group experienced the haptic system as very intuitive. Additionally, the system is capable of running completely remotely via a two-laptop setup, which has been tested at distances up to 100km.

Conclusion

An intuitive, haptic semi-autonomous teleoperation system is created for the execution of a plunger removal intervention. Both in a static and dynamic scenario, an improvement of the operating time is observed compared to the current glove-based method (2 to 3 min). The system can run fully remotely and was found to be very intuitive by the user group.