Journal of Pharmaceutical Innovation最新文献

Purpose

The purpose of this study was to formulate and evaluate nanostructured lipid carriers (NLCs) of the poorly water soluble anticancer drug Flutamide.

Methods

Flutamide-loaded NLCs were formulated by the melt-emulsification ultrasonication method using solid lipid (Precirol ATO 5), liquid lipid (Linseed oil) and surfactants (Tween 80 and Koliphor RH 40). Box Behnken design using 3 factors and 3 levels were utilized to study key cause impact relationship between independent and dependent variables.

Results

The optimized Flutamide NLCs further evaluated for different parameters. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies showed spherical morphology and smooth texture of Flutamide NLCs. The optimized Flutamide-loaded NLCs showed high encapsulation efficiency of 97.7 ± 4.98%. The in vitro drug release of 88.15 ± 1.16% was shown by optimized Flutamide NLCs and followed Korsemeyer-peppas kinetics with Fickian diffusion as a drug release mechanism. The in vitro cell line studies on PC3 cells showed satisfactory results.

Conclusion

NLCs could have great potential to deliver Flutamide by oral route in the treatment and management of prostate cancer by oral route.

Purpose

The bioefficacy of accessible chemical structures has been established, leading to some optimization to address these constraints.

Methods

This study aimed to identify the computational interactions of molecular docking, molecular simulations, and Network Pharmacology, which were used to predict the anticancer efficacy of Capsaicin and Quinidine complexes.

Results

The molecular docking studies exhibited that the identified phytocompounds had excellent binding energy against all of these target receptors, with 6OP9 affinity binding energy at -8.62 kcal/mol and for 3VHE at -8.18 kcal/mol. Molecular dynamics simulation for 100 ns of MD studies with RMSD and RMSF plots indicated that the ligand is stable, as it establishes interactions within active site residues such as LYS868, ASP1046, PHE1447, LEU14035, and LEU1099, followed by hydrogen bond interactions with THR768, ASP833, PHE834, LEU726, SER728, VAL734, and MET801. Based on human intestinal absorption, bioavailability score, P-glycoprotein, and BBB penetrant data, these are positive physiochemical inhibitors of Capsaicin and Quinidine. In network pharmacology, the essential genes identified were associated with cancer development (HER-2, HER-3), not specific to those that play a role in the carcinogenesis of the breast as well discussed by the targeted therapy trials mentioned above, that is, VEGFR1-3 and FGFR2 versus identification of progression-related genes involved, including ESR1, SRC, and HSP.

Conclusions

In vivo studies are needed to confirm the anticancer action of cancer regulatory proteins, and clinical trials are required to prove its safety and efficacy in other human subjects.

Background

Psoriasis is a chronic inflammatory skin disorder characterized by the development of red, scaly patches (National Psoriasis Foundation). It affects a significant portion of the global population, with estimates suggesting around 2% worldwide and 0.44% in India. Acitretin, a second-generation retinoid derived from vitamin A, emerged as a recognized treatment for severe psoriasis following its approval by the US Food and Drug Administration (US-FDA) in 1997.

Aim

The objective of this study was to enhance the topical delivery of acitretin by formulating it into a transethosomal gel. Acitretin, being poorly water-soluble, has limited penetration into the deep layers of the skin. The incorporation of transethosomal technology in this formulation aims to enhance acitretin's penetration into the skin and potentially improve its bioavailability.

Method

Transethosomes were prepared using the cold method. A 17-batch Box-Behnken design (Design-Expert® software) was employed to optimize the formulation with varying concentrations of lipid, ethanol, and Tween 80. Entrapment efficiency, vesicle size, and zeta potential were determined to characterize the transethosomes. The optimized batch containing acitretin-loaded transethosomes was then incorporated into a xanthan gum gel base. In vitro and ex-vivo and flux studies were conducted to assess drug diffusion and release patterns. Additionally, the formulation's irritancy and anti-psoriatic activity were evaluated in-vivo using Wistar rats.

Results

The Box-Behnken design optimization identified a formulation with a combination of 38.1% ethanol, 1.9% lipid, and 0.3% Tween 80 as optimal. This formulation exhibited a vesicle size of 105 nm, an entrapment efficiency of 80.4%, and a zeta potential of -28.25 mV. An optimized transethosome-based gel formulation was developed for its potential application in psoriasis therapy. The gel underwent a comprehensive evaluation of its physicochemical properties (pH, viscosity, spreadability) and in-vitro antimicrobial efficacy against Staphylococcus aureus. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and zone of inhibition assays were employed, demonstrating the gel's potent antibacterial activity. In-vivo studies on Wistar rats were subsequently conducted to evaluate skin irritation and imiquimod-induced anti-psoriatic activity. A pharmacokinetic study further compared the bioavailability of the transethosome gel with a conventional gel formulation. Notably, the results revealed a significant enhancement in bioavailability with the Transethosomal formulation.

Conclusion

The acitretin-loaded transethosomal gel demonstrated enhanced skin penetration and efficacy in managing psoriasis, achieving better outcomes than conventional treatments, while maintaining biocompatibility and minimal local side effects such as erythema, edema, and irritation.

Purpose

Lycopene (LYC) is a natural carotenoid, which has antioxidant, anti-inflammatory and anti-cancer properties. Nevertheless, its inherent instability has hindered oral formulation and administration due to sensitivity of LYC to environmental conditions.

Methods

We tested different methods of tomato extraction to provide an extract with the highest yield of extracted LYC and prepared double coated pellets to enhance the physiochemical properties of LYC and improve its efficacy. The pellets were prepared by extrusion-spheronization technique and were coated by Eudragit L 100 − 55 to protect LYC from gastric acidic pH. To increase the protection of LYC from environmental conditions and provide an opaque, thick layer on the pellets, a layer of sugar-coating was added around the film-coated pellets. Particle size, sphericity, morphology, dissolution, and stability of the pellets were analyzed.

Results

The highest yield of extracted LYC achieved by the mixture of ethyl acetate-acetone (1:1 v/v) applying for 5 h at 40 °C. The dissolution test of the pellets demonstrated that the dual-coating could protect LYC in the simulated gastric medium and release it in the simulated intestinal medium. The result of the stability test confirmed the efficiency of the additional sugar-coat to the film layer of the pellets since the amount of remaining LYC in dual-coated pallets was significantly higher than the film-coated pellets after six months of accelerated stability test.

Conclusion

The dual-coating of the pellets could protect LYC from environmental conditions and increase its stability. However, addition of substances to the formulation which might maximize the stability of LYC requires further study.

Purpose

Here, utilizing of microneedle roller as a physical enhancer of drug permeation through third-degree burn eschar has been investigated. This study was also conducted to investigate the effect of physicochemical properties of different drugs on permeation through perforated and unperforated eschar.

Method

1000 μm and 1500 μm height microneedle rollers were used to study the effect of microneedle pretreatment on permeation of diclofenac sodium, vancomycin hydrochloride, and sirolimus through human third-degree burn eschar. Optical microscopy and histological sectioning were used to visualize perforation and characterize the penetration depth, respectively. Franz-diffusion cells were utilized to study the permeation over 10 h.

Results

There were visible pores in eschar after treatment for both microneedle heights. Despite different physicochemical properties of drug models, microneedle rollers enhanced the permeation percentage through eschar in the range of 1.4 to 3.7 times for 1000 μm and 3.3 to 5.53 times for 1500 μm microneedle. Diclofenac as a molecule with the lowest MW and moderate log P had the highest permeation percentage in unperforated and perforated conditions. In the control condition, despite the higher MW of vancomycin compared to sirolimus, a higher percentage of vancomycin (about 2.7 times) permeated through eschar, indicating the higher permeability of hydrophilic drug in unperforated eschar. This behavior was also observed after eschar treatment with both heights of microneedle rollers.

Conclusion

Commercially available microneedle rollers enhance the drug permeation through eschar. Microneedle pretreatment has the potential to be used for burn management in situations where early eschar removal is not possible.

Purpose

This study aims to meticulously analyse the trends and recurrent challenges that emerge from Warning Letters (WLs) issued by the United States Food and Drug Administration (USFDA), focusing on current Good Manufacturing Practices (cGMP) voilations. By investigating the organizational, procedural, and systemic factors that precipitate these non-compliances, the research provides a comprehensive overview of the obstacles to cGMP adherence.

Methods

The framework for this study involved a detailed statistical analysis of WLs issued from 2019 to 2024, accessible through the USFDA database. Each letter was categorized and analysed according to violation type, frequency, and underlying causes. This approach facilitated a nuanced understanding of the major and minor compliance issues affecting the pharmaceutical industry.

Results

The analysis of total 186 WLs reveals a predominance of violations related to cGMP standards and adulteration of drug products, pinpointing these areas as significant compliance. The study further categorizes and discusses minor violations to offer a holistic view of the compliance landscape in pharmaceutical insdustries.

Conclusion

The findings from the WLs suggests a critical need for enhanced regulatory vigilance and quality assurance processes within pharmaceutical companies. The recurrent nature of certain violations highlights potential systemic flaws in how cGMP guidelines are implemented and adhered to across the industry. This research advocates for a proactive regulatory strategy by forecasting regulatory trends and identifying cGMP enforcement challenges, aiming to strengthen quality, streamline inspections, reduce compliance discrepancies, and improve public health outcomes.

Purpose

The primary aim of this study was to optimize, characterize, and test a controlled-release organogel of nifedipine for oral delivery. The formulation employed 12-hydroxy stearic acid as a gelator with soybean oil as a base. This research sought to investigate the potential of this organogel system to provide a controlled release alternative for nifedipine administration.

Methods

Preformulation studies and drug-excipient compatibility tests were conducted for nifedipine and the selected excipients. A controlled release organogel was created using the heating method. A quadratic model was applied to design formulations (F1-F14) with varying concentrations of 12-hydroxy stearic acid and distinct cooling rates (gradual and quick cooling) at five levels, utilizing a one-factor response surface approach. The prepared formulations were evaluated using various assessment parameters. Design Expert 7.0 was employed to statistically derive the optimized batch. Differential scanning calorimetry and Fourier-transform infrared spectroscopy were used to compare the preformulation test results between nifedipine and the excipients.

Results

The optimized controlled-release organogel exhibited a drug release profile of 86.02% at 10 h, which increased to 96.04% after 12 h. The data for the optimized formulation revealed a significant correlation between expected and actual responses, indicating the efficacy of the quadratic model and the response surface approach in predicting formulation behavior.

Conclusions

The study concluded that an organogel formulation using 12-hydroxy stearic acid as an organogelator and soybean oil as a base could be beneficial for controlled-release formulations of nifedipine. The results suggest that this organogel system is a viable alternative for the controlled release of nifedipine, offering a promising method for its oral administration.

Purpose

Ampoules are widely used in medical settings worldwide. However, there is a lack of research comparing the safety and efficiency of various ampoule-opening methods. This exploratory study aimed to compare several parameters regarding the safety and efficiency of an innovative ampoule opener with two other methods for opening ampoules.

Methods

Six participants were recruited from a university and a medical center in Eastern Taiwan. They were instructed to open ampoules of three different capacities (2 mL, 5 mL, and 20 mL) in duplicates using three distinct methods: by hand, with scissors, and with an innovative ampoule opener. This led to a total of 18 ampoules being opened per participant.

Results

Analysis with Generalized Estimating Equations revealed significant risks associated with using scissors, especially for larger ampoules, resulting in more spikes, indentations, and glass shards. Moreover, opening a 2 mL ampoule with scissors took significantly longer than doing so by hand. Conversely, the correct use of ampoule openers was found to result in fewer spikes and glass shards.

Conclusion

This exploratory study showed the importance of using ampoule openers and providing adequate training in their use to improve safety for healthcare workers and patients. Our findings also serve as a preliminary guide for future research to help in developing comprehensive safe-opening guidelines and inform best practices in healthcare settings.

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