Journal of Pharmaceutical Innovation最新文献

Purpose

Intravaginal drug administration offers a notable alternative to traditional oral delivery methods, allowing for precise targeting of effects both locally and systemically. In response to this, there has been a notable increase in the development of advanced in silico techniques for predicting drug permeability. These methods prove to be advantageous by bypassing the lengthy and resource-intensive processes typically associated with in vitro and in vivo experiments.

Methods

This particular study delved into the creation of in silico models specifically tailored for predicting vaginal permeability. The models were meticulously constructed using SMILES descriptors and local molecular graph invariants, ensuring a conformation-independent QSAR model. Leveraging a Monte Carlo optimization strategy, the models were iteratively refined across three distinct molecular splits for training and testing purposes.

Results

For the best developed QSAR model following statistical parameters were obtained for training set r² = 0.7152, CCC = 0.8340, IIC = 0.7572, q² = 0.7011, RMSE = 0.0055, MAE = 0.0044 and F = 196; and for test set r² = 0.8657, CCC = 0.8902, IIC = 0.6180, q² = 0.8412, R_m² = 0.6722, RMSE = 0.0040, MAE = 0.0030 and F = 168.

Conclusions

These results underscored the exceptional predictive capabilities and robustness of the QSAR models developed in this study. Furthermore, the analysis pinpointed key molecular fragments derived from SMILES descriptors that significantly influence placental permeability. Given the prevalence of SMILES notation in most molecular databases, these well-constructed QSAR models can effectively serve as a rapid and precise screening tool for evaluating vaginal permeability.

Graphical Abstract

Purpose

In this study, coconut oil (liquid lipid) and shea butter (solid lipid) were used to formulate ciprofloxacin-loaded nanoparticles (nanostructured lipid carriers, NLC, solid lipid nanoparticles, SLN, or nanoemulsions, NE) which were then evaluated for pharmaceutical and antibacterial properties.

Methods

The nanoparticles were produced by hot homogenisation high-pressure technique with a combination of the solid and liquid lipids for the NLC, solid lipid alone for the SLN, and liquid lipid alone for the NE. The nanoparticles were characterised by size, polydispersity index (PDI), zeta potential, FTIR, drug entrapment efficiency, drug dissolution (in vitro) and release kinetics, antibacterial action, and stability.

Results

The nanoparticle sizes ranged from 157.0 ± 83.8 to 205.4 ± 95.6 nm, with PDI of 0.229–0.255, and zeta potential of -25.2 ± 5.6 to -45.3 ± 6.1mV. FTIR revealed no interaction between the drug and lipids. Drug entrapment was > 95.0%; only NLC had a t₈₀ of < 45 min. Drug release kinetics followed the Korsmeyer-Peppas model showing a Super case II transport mechanism. The ranking of the antibacterial activity was SLN > NLC > NE against both Staphylococcus aureus and Salmonella typhi. Stability studies indicated that phase separation occurred, drug content was reduced (p > 0.05), while release kinetics and mechanism remained largely unchanged.

Conclusion

Coconut oil and shea butter lipids were effective for the formulation of ciprofloxacin-loaded nanoparticles, with the solid lipid nanoparticles and nanostructured lipid carriers demonstrating suitable pharmaceutical properties and antibacterial activity.

Purpose

The present study aims to overcome the poor oral bioavailability of ezetimibe (EZ), a selective Biopharmaceutics Classification System (BCS) Class II cholesterol absorption inhibitor drug. EZ-loaded nanostructured lipid carriers (EZ-NLCs) were dried by lyophilization and incorporated in a convenient oral solid dosage form to enhance its dissolution, and absorption and increase patient compliance. Response surface methodology (RSM) was employed to systematically optimize formulation variables, improving the efficiency of disintegration and drug release characteristics.

Methods

RSM was adopted to study the effects of (A) increasing the amount of the super-disintegrant, crosscarmelose sodium, (CCS), and (B) varying the ratio between the used drying excipients Avicel and mannitol (A: M) on the disintegration time (R1), and the percentage drug released after 24 h (R2). Thirteen EZ-NLCs tablets were prepared and subjected to pre-compression and post-compression evaluation. Furthermore, a bioequivalence study was conducted by administering EZ-NLCs and ezetrol^® tablets to Sprague Dawley male rats.

Results

The optimized EZ-NLCs tablet (prepared with the ratio of Avicel: mannitol (7.5:0) using 30 mg CCS), revealed a disintegration time of 3.85 ± 0.03 min, and 98 ± 3.09% of the drug were released at the end of the 24 h. EZ-NLCs tablet displayed a maximum concentration (Cmax) of 3.57 ± 0.27 ng/mL and an area under the curve (AUC_0− 24) of 22.44 ± 2.68 ng.hr/mL, while those of ezetrol^® were 2.79 ± 0.15 ng/mL and 15.36 ± 0.86 ng.hr/mL, respectively.

Conclusion

The assessed relative bioavailability demonstrated the superiority of EZ-NLCs tablet over ezetrol^® with 1.5 fold improvement which proves that EZ-NLCs tablet could be a good candidate to enhance the oral bioavailability of EZ.

Graphical Abstract

Purpose

This study aimed to develop a normal-phase TLC densitometry/ high-performance thin-layer chromatography (HPTLC) protocol, assisted with an Automatic Development Chamber 2 (ADC 2) for the efficient and robust pharmaceutical quantification of a thrombopoietin receptor agonist Eltrombopag Olamine (ELTO) using experimental design.

Methods

The effect of various factors on HPTLC outcomes has been studied using the Box-Behnken Design (BBD) to enhance method robustness. The ADC 2 was employed as an advancement in the development of a validated normal-phase HPTLC protocol, improving the method’s reproducibility and accuracy.

Results

TLC densitometry scans were performed at 399 nm in reflectance mode optimizing the retention of ELTO at an R_f value of 0.47 ± 0.02. The application of ADC 2 during the development minimized the impact of temperature and humidity. The BBD, supported with response surface methodology (RSM), was used to assess the method’s operable design region for increased robustness. The established linearity range was from 250 to 1500 ng per spot, with a regression coefficient (r²) of 0.9998. The developed protocol was validated according to Q2(R2) recommendations of the International Council for Harmonization (ICH).

Conclusion

NP-HPTLC is unique, efficient, precise, reproducible, and robust for the rapid quantification of ELTO. The method also uses minimal amount of organic solvents compared to well-known techniques such as high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). The protocol is timesaving, allowing the simultaneous analysis of multiple samples, making it an effective alternative for determining ELTO in pharmaceutical formulations.

Graphical Abstract

Purpose

Nanotechnology creates materials for medical purposes, such as nanocarriers or smart polymers that target and treat diseases like cancer.

Methods

In this study, hybrid carriers based on doxorubicin/poly(N-vinylcaprolactam) (DOX-PVCL) and doxorubicin-loaded niosome /poly(N-vinylcaprolactam) (DOX-Nio-PVCL) have been constructed as thermoresponsive polymers. At first, PVCL was synthesized and purified. Then, the DOX-Nio was prepared by the thin layer evaporation method and loaded into the PVCL. Furthermore, doxorubicin was loaded on PVCL by the same method. The structure features and morphology of the synthesized particles were determined using Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), Raman spectroscopy, and electron microscopy. The synthesized particles’ size was measured at 25˚C and 37˚C by dynamic light scattering (DLS).

Results

The lower critical solution temperature (LCST) was determined and showed 32.5, 28.5, 28.5 ˚C values for PVCL, DOX-Nio-PVCl, and DOX-PVCL dissolved in phosphate-buffered saline, respectively. The release behavior of doxorubicin showed that the synthesized formulations had more potential release at pH 5.5 than pH 7.4. Evaluation of the cytotoxicity of PVCL on MCF-7 did not show any significant toxicity for concentrations 5.8–29 µg/mL. MCF-7 cell viability was investigated in the presence of DOX, DOX-Nio, DOX-Nio-PVCL, and DOX-PVCL at a final concentration of 29 µg/mL and 1.1 µg/mL of polymer and drug, respectively. Our results showed the highest MCF-7 cell death in DOX-PVCL-treated cells.

Conclusion

While the synthetic polymer displayed promising abilities in eliminating cancer cells, further study is necessary to explore its potential as a medicinal treatment, particularly in understanding its impact on in vivo structures.

Purpose

The primary purpose of this perspective article is to challenge the conventional approach of spray angle measurement in pharmaceutical sprays, which has long relied on the formula θ = (:{text{tan}}^{-1}frac{l}{r}). This article introduces and justifies the use of the correct formula, θ =(:2{text{tan}}^{-1}frac{r}{l}), which provides a more accurate method for calculating spray angles. Accurate spray angle measurement is crucial for determining drug dispersion and coverage, ensuring uniform deposition on target areas such as wounds and topical treatments,optimizing formulation and device performance. Inaccurate measurement may lead to under-dosing or over-dosing. Consistent spray patterns also guarantee reproducibility, which is essential for maintaining product quality and ensuring effective clinical outcomes.

Methods

A comprehensive review of existing literature was conducted to identify and analyse the use of the θ = (:{text{tan}}^{-1}frac{l}{r}) formula in spray angle measurement. The mathematical and geometric principles underlying both formulas were examined and compared. Additionally, the implications of using the correct formula, θ =(:2{text{tan}}^{-1}frac{r}{l}), were explored in the context of pharmaceutical spray performance.

Results

The analysis revealed that the traditional formula, θ = (:{text{tan}}^{-1}frac{l}{r}), often leads to inaccuracies in determining the spray angle, which can result in suboptimal spray performance and drug delivery. The correct formula, θ =(:2{text{tan}}^{-1}frac{r}{l}), addresses these inaccuracies, offering a more precise and reliable method for measuring spray angles ensuring accurate spray characterization.

Conclusion

This article advocates for the adoption of the θ = (:2{text{tan}}^{-1}frac{r}{l})formula as the standard for spray angle measurement in pharmaceutical sprays. By correcting the longstanding error in the methodology, this new approach enhances the accuracy of spray characterization, ultimately contributing to better drug delivery outcomes. Further research and validation are encouraged to solidify this method as the industry standard.

Background

Lornoxicam microspheres are promising for targeted, controlled, or extended drug release, and the incorporation of mucoadhesive properties can significantly enhance bioavailability and absorption. This study focuses on the development of bioadhesive microspheres utilizing the ionotropic gelation and emulsion crosslinking methods.

Purpose

The primary aim of this research is to formulate bioadhesive microspheres of Lornoxicam using Sodium Alginate, Carbopol 934, and Chitosan as polymers, while simultaneously evaluating Lornoxicam’s interactions within Alginate-Carbopol 934 and Chitosan matrices through molecular dynamics simulations.

Methods

Formulations T1 to T4 employed drug-to-polymer ratios of 1:1, 1:2, 1:3, and 1:4 for Sodium Alginate and Carbopol 934, while formulations T5 to T8 utilized the same ratios for Chitosan and glutaraldehyde as the crosslinking agent. Comprehensive assessments were conducted on particle size, drug entrapment efficiency, and dissolution rates. Molecular dynamics simulations were performed to analyze Lornoxicam’s interactions within the polymer matrices.

Results

Formulation T7 emerged as the optimal formulation based on extensive evaluation tests. Molecular dynamics simulations revealed stable RMSD values for Lornoxicam across both matrices, with the Chitosan matrix displaying greater fluctuations. Notably, stronger hydrogen bond interactions were observed in the Chitosan matrix, which corresponded to a marginally higher binding energy than the Alginate-Carbopol 934 matrix.

Conclusion

These findings indicate that Chitosan may significantly enhance the pharmaceutical potential of Lornoxicam as a drug delivery system, highlighting the need for further exploration of its therapeutic applications.

Purpose

The study intended to develop and investigate controlled release non-effervescent floating polymeric tablets of Clarithromycin and Pantoprazole to enhance their bioavailability by prolonging the gastrointestinal transit time of drugs, a system for Helicobacter pylori elimination.

Methods

The gastro-retentive tablets were prepared via direct compression method using different concentrations and combinations of hydroxypropyl methylcellulose (HPMC) K4M, Carbopol and guar gum as hydrophilic polymers and Avicel 102 as a filler. The pre-compression solid mixture was characterized for angle of repose and compressibility index, applying Hausner’s ratio to predict the flowability, as well as fourier transform infrared spectroscopy for drug-excipient interaction evaluation. The prepared tablets were investigated for dimension, hardness and friability, weight variation and content uniformity, swelling index, density, buoyancy and in-vitro drug release.

Results

All the formulations exhibited desired floating and flow attributes. Solid-state characterization revealed no chemical interaction between excipients and the drugs. With reference to in-vitro study results, all formulations, except F7, have displayed slow drug release and reduced burst effect (F6). The lowest lag buoyancy of 5 min was achieved in F2. This study develops a non-effervescent floating system for dual drug delivery to enhance gastric residence time, thereby optimizing local therapeutic effects. This innovative approach aims to reduce dosing frequency and associated side effects, improving patient compliance and treatment efficacy for gastric ulcer. This innovative approach can provide effective ulcer healing with shortened treatment time, reduced side effects and improved patient compliance.

Conclusion

This study also highlights the effectiveness of non-effervescent approach to improve dissolution and bioavailability.

Graphical Abstract

Introduction

The generation of biofilms by bacteria has become a major factor in the rise of antibiotic resistance. Lipid nano-capsules (LNCs) have recently emerged as an innovative platform for drug delivery, due to their unique properties and ability to carry a wide array of therapeutic chemical compounds.

Objectives

The objective of this research was to create, optimize, and evaluate the antibiofilm efficacy of a peppermint oil emulsion (o/w) containing levofloxacin against resistant bacteria via biofilm formation.

Methods

Essential oils, particularly peppermint oil known for its antifungal properties, were employed instead of traditional medium chain triglycerides to formulate lipid nanocarriers, utilizing alternating surfactant types (Solutol HS 15 and Cremophor EL) and differing oil to surfactant ratios (2:1 and 1:1). The LFX-LNCs formula, with a 2:1 oil to surfactant ratio, was selected for further investigation due to its physical properties, including particle size, zeta potential, transmission electron microscopy, and polydispersity index. The antibacterial efficiency of LFX-LNCs was evaluated, revealing their ability to eradicate established biofilms of Gram-negative pathogens, including Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), as well as Gram-positive strains such as Staphylococcus aureus (S. aureus).

Results

The mean particle size of LFX-LNCs varied from 30.86 ± 0.54 nm to 68.36 ± 0.56 nm, demonstrating a narrow size distribution, a negative zeta potential (-1.56 ± 0.24 to -20.2 ± 2.15 mV), and a polydispersity index (PDI) ranging from 0.062 ± 0.006 to 0.26 ± 0.002. Lipid nanocapsules generally exhibit a spherical morphology within the nanometric size range when analyzed by transmission electron microscopy (TEM). The antimicrobial activity assessment revealed that EL 2:1 exhibited the most significant antimicrobial efficacy, characterized by a reduced particle size and an inhibition zone measuring up to (2.43 ± 0.24 cm), demonstrating promising results against several pathogenic strains, including P. aeruginosa, S. aureus, and E. coli.

Conclusion

This study illustrates the efficacy of LFX-LNCs in the treatment of non-healing wounds infected with biofilm-forming bacteria.

Graphical Abstract

Background

The treatment of recurrent vaginal fungal infections by topical application of antifungal agent is limited mainly due to poor solubility and low levels of the drug available at the site of action in the affected tissues. For this reason, research is being done on novel drug-delivery technologies and new therapeutic compounds. Posaconazole (POS) is a broad-spectrum antifungal reported to be effective in managing serious infections and drug-resistant fungal strains.

Purpose

In the present study, lipid polymer hybrid nanoparticles (LPHNP) were prepared to achieve site-specific targeting and improve tissue uptake of POS. A sustained release profile and higher drug encapsulation are both rendered possible by the structural benefits of polymers and the biomimetic characteristics of lipids.

Material and Methods

In the present study, LPHNP were prepared using POS, polycaprolactone (PCL), soya lecithin, and polyvinyl alcohol (PVA) as structural constituents by emulsification followed by solvent evaporation. The formulation batches were subsequently optimized using a 3-factor 3-level Box Behnken statistical design. Particle size, zeta potential, surface morphology by transmission electron microscopy (TEM), drug entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), and in vitro drug release were all employed to characterize the formulations. A cell viability assay was used to conduct cytotoxicity studies of the LPHNP on the SiHa cell line. The cellular uptake was assessed using a confocal laser scanning microscope and flow cytometry.

Results

The particle size, polydispersity index (PDI), and zeta potential of the optimized LPHNP batch were found to be 465 ± 58.13 nm, 0.17 ± 0.07, and -12 mV respectively. The entrapment efficiency was found to be 90.92 ± 0.22%. The antifungal activity of POS-loaded LPHNP was significantly higher than the pure drug. The release of drug from the LPHNP system was observed to be sustained for up to 24 h. The in vitro cell cytotoxicity (MTT assay) and cellular uptake were evaluated using SiHa cell lines. The MTT assay of the developed LPHNP formulation demonstrated negligible cytotoxicity as compared to that of pure POS. The cell uptake studies by flow cytometry showed greater cell internalization of the formulation (58.4% after 4 h incubation) owing to the smaller particle size of the nanoparticles. Similar results (78% after 4 h incubation) were observed in confocal microscopy indicating probable higher therapeutic efficacy for deep-seated fungal infections.

Conclusion

Conclusively, LPHNP is a promising drug delivery system for vaginal targeting of therapeutic moieties.