Journal of Pharmaceutical Innovation最新文献

Purpose

This study aimed to investigate the impact of moisture content on the assay of amoxycillin and potassium clavulanate dry oral suspension.

Methods

For this purpose, 35 samples of different brands and strengths of amoxycillin and potassium clavulanate dry oral suspension were collected from various high-humidity locations in India. All collected samples were subjected to moisture content test, while selected samples were subjected to amoxycillin and clavulanic acid assay; both were performed as specified in the corresponding Indian Pharmacopoeia (IP) 2022 monograph for amoxycillin and potassium clavulanate dry oral suspension.

Results

The moisture content of the samples ranged from 4.6% to 9.3% for amoxycillin 200 mg/clavulanic acid 28.5 mg per 5 ml strength and from 6.3% to 10.5% for the amoxycillin 400 mg/clavulanic acid 57 mg per 5 ml strength. Of the 35 samples analysed, 2 samples of amoxycillin 200 mg strength failed the IP 2022 moisture limit (not more than 8.5%), with observed values of 9.3% and 9.1%. The amoxycillin content in the two failed samples was 74.52% and 73.36%, respectively, which is below IP 2022 limits (90.0%–120.0%). However, clavulanic acid content remained within acceptable IP 2022 limits (90.0%–125.0%).

Conclusion

These findings indicate that moisture may affect amoxycillin content, stability, and assay performance of amoxycillin and potassium clavulanate dry oral suspension, suggesting that moisture content could be a vital quality control parameter in its formulation and storage.

Purpose

This study compared the phytochemical and antioxidant profiles of argan kernel oil (AMO) and argan leaf extract (EEL) from the Stidia region of Algeria to characterize and evaluate the lesser-studied bioactive compounds of argan leaves.

Methods

Standard colorimetric assays measured total phenolics, flavonoids, and condensed tannins. Chemical profiles of the two extracts were performed using GC-MS. Antioxidant activity was assessed using four assays: FRAP, DPPH radical scavenging, β-carotene bleaching, and Total Antioxidant Capacity (TAC).

Results

GC-MS identified oleic acid (45.16%) and linoleic acid (32.59%) as predominant in AMO, whereas the leaf extract was rich in quinic acid (42.32%). EEL contained significantly higher concentrations of total polyphenols (193.48 ± 13.96 mg GAE/g DW) and flavonoids (445.88 ± 5.20 mg QE/g DW) compared to the oil. AMO exhibited the highest antioxidant activity in the ferric reducing antioxidant power (FRAP) assay (0.200 ± 0.04 mg/mL) and β-carotene bleaching assay (0.070 ± 0.02 mg/mL). In contrast, EEL showed stronger free radical scavenging (IC₅₀: 0.084 ± 0.03 mg/mL) and higher total TAC (IC₅₀: EEL 0.018 ± 0.02 mg/mL).

Conclusion

These findings reveal distinct bioactive profiles, highlighting that EEL is a better source of phenolics, flavonoids, and quinic acid with strong radical scavenging activity, while AMO demonstrates greater potential against lipid oxidation. This comparative investigation gives new evidence for the distinct benefits of argan leaves and oil in nutraceutical and pharmaceutical applications. However, based on the foundational in vitro nature of the antioxidant assays, further in vivo and clinical studies are required to fully validate the therapeutic potential of these extracts.

Purpose

Topical delivery of lidocaine is often limited by poor aqueous solubility, restricted skin permeation, and rapid drug release. This study aimed to improve the water solubility of lidocaine and to develop a microemulsion (ME)-based gel capable of providing controlled release and enhanced ex-vivo skin permeation.

Methods

Lidocaine-loaded microemulsions (MEs) were prepared using castor oil, Tween 80, and propylene glycol through aqueous titration and optimized using a Box–Behnken Design. All prepared MEs were characterized for droplet size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), and thermodynamic stability. The optimized ME was further examined by transmission electron microscopy (TEM). This optimized ME was then incorporated into a Carbopol gel base to obtain a ME gel suitable for topical application. In-vitro release and ex-vivo permeation studies across excised goat skin were performed for the optimized ME gel and compared with a conventional lidocaine gel. Release kinetics were evaluated using mathematical models. Stability studies were conducted at 25 ± 2 °C/60 ± 5% RH and 4 ± 2 °C for 60 days.

Results

The developed MEs exhibited nanosized droplets (< 100 nm), low PDI (0.27), ZP ranging from − 31.5 to − 9.43 mV, high EE% (> 90%), and satisfactory thermodynamic stability. TEM confirmed spherical nanoscale droplets. The ME gel demonstrated suitable viscosity and spreadability for topical use. In-vitro release showed sustained diffusion-controlled behavior (85.6 ± 2.7% in 24 h) following Higuchi kinetics (R² = 0.971). Ex-vivo permeation from the ME gel was significantly higher than the conventional gel, with approximately two-fold higher steady-state flux (26.57 ± 2.41 µg/cm²/h). Stability assessment showed no significant changes in PS, PDI, ZP, EE%, pH, or viscosity over 60 days.

Conclusion

The lidocaine-loaded ME gel improved drug solubility, provided controlled release, and enhanced ex-vivo permeation while maintaining physicochemical stability. These findings support its potential as a formulation-level strategy for topical lidocaine delivery, pending further in-vivo and pharmacodynamic evaluation.

Niosomes are a novel vesicular drug delivery system made from the self-build of non-ionic surfactants in aqueous media. Niosomes vesicles can encapsulate hydrophilic and lipophilic drugs in an aqueous layer or in vesicular lipid membrane. The purpose in this study was to formulate clotrimazole loaded niosomes using Span 60 with cholesterol in three ratios (w/w) namely; (1:1), (2:1), and (3:1), along with three different amounts of total lipids; 150, 225, and 300 mg. All the prepared niosomal formulas had high encapsulation efficiency (EE%), small vesicle size (VS), and high zeta potential (ZP) values. Software of Design Expert^® was utilized for optimization of the prepared niosomes applying 3² complete factorial design. The results showed that the optimized formula is F5, which was composed of Span 60: cholesterol with a ratio (2:1) (w/w) and 225 mg total lipid content. F5 had EE% of 95.83 ± 0.17%, VS of 598.30 ± 7.92 nm, polydispersity index of 0.73 ± 0.07, and ZP of -56.75 ± 2.47 mV. It showed spherical shape carriers without aggregation. Further, a stability study at 4 °C and 25 °C after 45 and 90 days indicated the high stability of F5. Moreover, F5 exhibited a slower in vitro release and a greater permeability across the rabbit cornea compared with clotrimazole suspension. Besides, F5 showed a greater inhibition of Candida albicans development in comparison with clotrimazole suspension, detected via 2,3-bis (2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction method. Additionally, the histopathological inspection on mature male albino rabbits’ eyes verified the safety of F5 after ocular administration.

Graphical Abstract

Aim

In the present study, matrices of metoprolol tartrate (200 mg) were developed with two individual polymers (Ethocel 7 premium and Ethocel 7FP premium) at various w/w drug-to-polymer ratios (10:3, 10:4, and 10:5), with a filler (spray-dried lactose) and lubricant (magnesium stearate).

Methodology

The direct compression method was used to prepare the matrices, and their diameter, thickness, friability, hardness, weight variation, in vitro dissolution tests (24-h drug release profiles), and uniformity of content were used to evaluate them.

Results

The matrices comprising Ethocel 10 FP at a 10:3 ratio showed pseudo-zero-order kinetics (n-value of 0.989), but the dissolving data from the test matrices and reference tablets did not match. The following pharmacokinetic characteristics were studied: Cmax (196.0 ± 0.025 µg/mL), half-life (11.210 ± 0.169), Tmax (4.11 ± 0.091 h), AUCo (2121.23 ± 0.215 µg.mL), AUCo-inf (4234.46 ± 0.105 µg.h/mL), Cl (0.013 ± 0.011 mL/min), and MRTo-48 h (11.48 ± 0.391). A correlation value of 0.9836 was found between the in vitro and in vivo results for the test-optimized matrices, showing a level-A relationship (point-to-point correlation between the percentages of drug released in vitro and the percentage of drug absorbed in vivo).

Conclusion

The matrices may increase patient adherence to once-a-day drug and therapy effects.

Aim

The current research aimed on the preparation of floating beads, which were then transformed into floating tablets to enhance gastric residence time.

Methodology

The beads (B1 to B5) were synthesized via the solvent evaporation method and subsequently characterized for Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC), flow properties, entrapment efficiency, percent yield, percent drug loading, floating behaviors, scanning electron microscopy (SEM), The optimized B5 (based on floating behaviors) was directly compressed into floating tablets, which were characterized for their physical and chemical properties, floating behaviors, and drug release mechanisms and compared with marketed products. Adult male rabbits were given B5 and a reference preparation to evaluate floating behaviors and pharmacokinetic parameters.

Results

The microbeads demonstrated free-flowing properties, and the findings adhered to USP standards. The particle size varied from 10 ± 0.16 to 10 ± 0.21 µm. The entrapment efficiency ranged from 72.42 ± 0.08 to 85.22 ± 0.12%. The percent yield was measured at 61.19 ± 0.02 to 67.52 ± 0.72%. The percent drug loading varied between 30.26 ± 0.25 and 38.29 ± 0.09%. The floating lag time ranged from 0.4 ± 0.22 to 1.0 ± 0.29 min, whereas the total floating time was recorded as 10.0 ± 0.16 to 12.5 ± 0.14 h. The surface morphology displayed roughness and irregularity. FTIR and DSC analyses validated that the drug and ingredients were not interacting with each other. The tablets' physical characteristics were found to comply with USP limits. B5 exhibited prolonged drug release rates for 20 h in 0.1 N HCl, achieving complete release in phosphate buffer at pH 6.8. The drug was released via pseudo-zero-order kinetics, characterized by swelling or erosion and non-Fickian mechanisms. The in vivo buoyancy of B5 was quantified at 20 ± 0.07 h. The pharmacokinetic parameters for B5 are as follows: t_max 5.03 ± 1.5 h, C_max 186 ± 0.59 µg/mL, T_1/2 10.0 ± 0.52 h, AUC_o 4832.1 ± 1.34 µg·h/mL, AUC_o-inf 6438 ± 0.42 µg·h/mL, MRT_o-24 14.65 h, and Cl 0.023 mL/min. The pharmacokinetic parameters for the reference tablets are detailed below: Tmax was 1.3 ± 0.06 h, C_max was 185 ± 0.24 µg/mL, T_1/2 was 5.65 ± 1.94 h, AUC_o was 38,581 ± 1.15 µg.h/mL, AUC_o-inf was 4347 ± 1.24 µg.h/mL, MRT _o-24 was 8.83 h, and Cl was 0.021 mL/min.

Conclusion

This study concludes that floating tablets can improve therapeutic effects by extending gastric residence time.

Background

Oxidative stress and inflammation are central to the pathogenesis of numerous diseases, including skin disorders, arthritis, and neurodegenerative conditions. UV-induced skin damage is largely attributed to the generation of reactive oxygen species (ROS), leading to oxidative stress, inflammation, and melanogenesis. Oxalis corniculata, a traditional medicinal herb rich in polyphenolic compounds such as syringic acid, exhibits notable antioxidant and anti-inflammatory activities. However, its therapeutic efficacy is limited by poor bioavailability.

Aim and Objective

This study aimed to develop, characterize, and evaluate a phytosomal delivery system of O. corniculata to enhance its biological efficacy. Additionally, a robust High-Performance Thin-Layer Chromatography (HPTLC) method was developed and validated for the quantification of syringic acid using an Analytical Quality by Design approach.

Methods

Phytosomes were prepared using phosphatidylcholine via the thin-film hydration method and evaluated for particle size, zeta potential, entrapment efficiency, and yield. A DoE-optimized HPTLC method using toluene: ethyl acetate: formic acid (7.5:2.5:0.5, v/v/v) was validated. Biological evaluation included in vitro antioxidant, anti-inflammatory, and UV protection assays. Molecular docking of syringic acid was performed against key protein targets (1N8Q, 1XKK), showing strong binding affinities (–6.4 and –6.1 kcal/mol, respectively), supporting its therapeutic potential.

Results

F5 was the optimized formulation with superior characteristics. The phytosome exhibited enhanced biological activities compared to the extract. SPF values improved significantly upon phytosomal encapsulation.

Conclusion

The integration of molecular docking, AQbD-based HPTLC quantification, and phytosomal delivery significantly enhanced the bioefficacy of syringic acid, supporting its potential in managing oxidative stress-induced skin disorders.

Graphical Abstract

Purpose

Ulcerative colitis is a chronic inflammatory disorder of the gastrointestinal tract often accompanied by extraintestinal complications, including neurobehavioral disturbances. This study aimed to evaluate the therapeutic potential of phenytoin in a rat model of acetic acid–induced colitis, with a focus on its anti-inflammatory effects and associated depression-like behavioral disturbances.

Methods

Forty male Wistar rats were randomly assigned to five groups (n = 8): Control, Acetic Acid (A.A), Phenytoin 30 mg/kg (intraperitoneal) (Phe 30), A.A + Phe 30, and A.A + Phe 60. Colitis was induced using 3% acetic acid. Macroscopic and histological evaluations of the colon were performed. Hippocampal NF-κB expression, inflammatory cytokines (TNF-α, IL-6), and regulatory mediators associated with neuroinflammatory modulation (Sirt1, PGC1-α, NRF2, HO-1) were quantified. Behavioral performance was assessed using the tail suspension and forced swim tests, and locomotor activity was evaluated by the open field test.

Results

Phenytoin treatment was associated with attenuation of colitis severity, reduction of the colon weight-to-length ratio, and improvement of histopathological alterations. It was accompanied by decreased NF-κB, TNF-α, and IL-6 expression in the colon and hippocampus, as well as increased hippocampal Sirt1, PGC1-α, NRF2, and HO-1 levels. Behavioral testing showed reduced immobility time with no effect on locomotor activity.

Conclusion

Phenytoin administration was associated with attenuation of acetic acid–induced colitis and concurrent changes in hippocampal inflammatory markers, together with improved depression-like behavioral outcomes in rats. These observations suggest a potential modulatory effect of phenytoin on gut–brain axis–related neuroinflammation, which merits further investigation.

Purpose

The goal of this study is to develop a High-Performance Thin Layer Chromatography method for baricitinib determination, which lowers the cost of analysis. Based on the literature survey, no previously published HPTLC method has been reported for the analysis of baricitinib, which encouraged the development of an HPTLC method with an environmentally friendly approach.

Method

A precoated TLC plate uses silica gel 60 F254 as the stationary phase, which is run in a mobile phase of ethyl acetate, toluene, and methanol in a ratio of 5:3.5:1.5 (v/v). Densitometric analysis was conducted at 310 nm in an absorbance mode. According to ICH Q2(R2) criteria, the developed method was validated. Stability was performed as per ICH guidelines Q1A(R2) and Q1B, which includes acid, alkaline, oxidation, neutral, thermal, and photolytic stress conditions.

Results

The Rf value of baricitinib was found to be 0.498 ± 0.037. The linearity range lies between 300 and 900 ng/band with a correlation coefficient of 0.9958. The developed method has been successfully applied to tablet formulation, with excellent recoveries ranging from 98.11% to 102%. The % content of the baricitinib tablet was found to be 98.2-100.35%. Baricitinib shows excellent sensitivity, with a limit of detection of 50 ng/band and a limit of quantitation of 153 ng/band. Stability was found to be more susceptible to alkaline degradation. Based on the greenness assessment tools, the analytical eco-score of 76 and the pictograms for GAPI, AGREE, and AGREE prep indicated the method’s greenness. The multi-color assessment (MA) tool further confirmed high sustainability (GEMAM 95.2%), excellent practicality (BAGI 90%), superior analytical performance (RAPI 87.5%) and good innovation (VIGI 60%). The final whiteness score is 83.2% with excellent score.

Conclusion

The developed method exhibited excellent greenness. A sensitive, precise, rapid, simple, and robust HPTLC method has been proposed and validated for determining the amount of baricitinib in API and pharmaceutical formulation and can be successfully applied for the routine quantitative analysis.

Background and Aim

Brucellosis is an infectious disease caused by different Brucella species which is a highly contagious infection that causes severe symptoms like fever, joint and muscle pain, neurological complications and many others that significantly affect quality of life. The associated symptoms will usually cause life discomfort for infected patients. In addition, brucellosis is a worldwide recognized major zoonotic disease that still present in low- and middle-income countries. The aim of this research is to evaluate the physical characteristic and the biological activity of ciprofloxacin-loaded with niosomes and compared them with the previously studied silica and silver nanoparticles for the possible improvement in drug potency and for lowering side effects.

Materials and methods

Silica, silver, and niosome nanoparticles were formulated as empty or loaded with ciprofloxacin and evaluated for their characteristics and activity. Ciprofloxacin loading efficiency, optical absorption, particles size and size distribution were measured. Moreover, cytotoxicity, minimum inhibitory, and hemolysis assays were done to determine the potency of nanoparticles-loaded with ciprofloxacin and to assess the possible side effects associated with the use of these nano-delivery systems. Cost analysis was performed by using cost of raw material for 14 local laboratories equipment market.

Results

Silica nanoparticles and nano-delivery system had better physical characteristic with a diameter of 80 and 113 nm, polydispersity index of 0.41 and 0.43 and with a higher zeta potential greater than 30mv respectively when compared to silver nanoparticles. All three nanoparticle systems improved the biological activity with MIC values of 0.046, 0.039 and 0.042 µg/ml for silver, niosome, and silica nanoparticles respectively with a concentration range between 25 and 1000 µg/ml compared to 0.72 µg/ml for free ciprofloxacin. Niosomes nano-delivery system had no effect on red blood cells haemolysis. Other nanoparticle systems had a measurable effect on red blood cells hemolysis. Finally, the cost of niosome formulation (17$) was much lower than silica nanoparticle (31$) and silver nanoparticles (74$) per 100 mg of loaded ciprofloxacin.

Conclusion

Niosome nano-delivery system may be used as a safer and more cost-effective alternative to metallic nanoparticles with a comparable biological activity, lower toxicity, and a lower cost.