Drug Development and Industrial Pharmacy最新文献

Objective: Bacterial infections caused by multidrug-resistant (MDR) strains pose a serious global health threat. This study aimed to evaluate the antibacterial efficacy of green-synthesized copper nanoparticles (G-CuNPs) against MDR strains of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella spp., and Escherichia coli.

Significance: Emerging MDR pathogens necessitate the development of novel, eco-friendly alternatives. G-CuNPs synthesized using Citrus pseudolimon peel extract may offer a biocompatible and sustainable approach to combating MDR infections.

Methodology: Clinical bacterial isolates were obtained from diagnostic specimens including urine, pus, wound swabs, sputum, and blood collected from hospitalized patients at a tertiary care hospital. Bacterial identification and antimicrobial susceptibility testing were performed using the VITEK 2 automated system. Phenotypic detection of metallo-β-lactamase (MBL) and extended-spectrum β-lactamase (ESBL) production was conducted. G-CuNPs were synthesized and characterized for physicochemical properties. Antibacterial activity was assessed using a CFU-based time-kill assay. Mechanistic studies included evaluation of cell membrane integrity, reactive oxygen species (ROS) generation, and DNA degradation. Interaction with bacterial enzymes was analyzed via molecular docking. Hemolytic and cytotoxicity assays were performed to assess biocompatibility.

Results: G-CuNPs (10 mg/mL) displayed potent antibacterial activity by disrupting cell membranes, inducing ROS accumulation, and degrading bacterial DNA. Molecular docking confirmed strong binding affinities to key bacterial enzymes. Compared to chemically synthesized CuNPs, G-CuNPs (Indian Patent No. 202111048797) exhibited minimal hemolytic and cytotoxic effects.

Conclusion: G-CuNPs demonstrate promising antibacterial potential and biocompatibility, highlighting their applicability in biomedical domains such as implant coatings and wound care. Further in vivo studies are warranted to validate their clinical utility.

Objective: To evaluate the anti-inflammatory activity and mechanism of Panaxadiol saponins (PDS), develop a PDS-based gel for periodontitis treatment, and evaluate its therapeutic efficacy using a rat model of periodontitis.

Methods: The anti-inflammatory effects of PDS were assessed using LPS-induced RAW264.7 cells. ELISA and RT-qPCR were performed to detect inflammatory factors; Western blotting analyzed MAPK/NF-κB pathway-related proteins. A single-factor experiment was used to examine the effects of the dosages of carbomer 940, propylene glycol, and triethanolamine on the properties of the PDS gel and to evaluate its in vitro release versus in vitro permeation and retention on oral mucosa. A rat periodontitis model was established by ligation plus high-sugar feeding, and the efficacy of PDS gel in ameliorating periodontitis in rats was evaluated using gingival index scoring, micro-CT, HE staining, ELISA, and RT-qPCR to assess the state of periodontal tissues and inflammatory responses, and salivary microbiota analysis using 16S rRNA sequencing.

Results: PDS significantly reduced NO, IL-6, IL-1β, and TNF-α release, inhibited their mRNA expression, and suppressed MAPK/NF-κB pathway-related proteins in LPS-induced RAW264.7 cells. The PDS gel exhibited good physicochemical properties, release performance, and mucosal permeability. PDS gel decreased gingival index, attenuated alveolar bone loss, reduced inflammatory cell infiltration, and lowered IL-6, IL-1β, TNF-α, and RANKL mRNA levels in serum and periodontal tissue. It also regulated and restored the balance of salivary flora.

Conclusion: PDS gel can inhibit the MAPK/NF-κB pathway-mediated inflammatory response, reduce bone destruction, and regulate bacterial dysbiosis, demonstrating good therapeutic prospects for periodontitis.

Background: Empagliflozin a sodium-glucose co-transporter 2 inhibitor, and Metoprolol succinate, a cardioselective β1-blocker, are co-formulated in a novel bilayer tablet currently under clinical evaluation. Reliable stability-indicating methods are required for simultaneous quantification of these drugs and to ensure environmental sustainability of pharmaceutical analysis.

Objective: To develop and validate a stability-indicating HPTLC method for concurrent quantification of EMP and METO in a novel combined oral formulation, in compliance with ICH Q2(R2) guidelines.

Methods: Chromatographic separation was achieved on HPTLC silica gel 60 F₂₅₄ plates using chloroform: methanol: toluene (3.0:2.5:4.5, v/v/v) as mobile phase. Detection was carried out at 222 nm. The method was validated for specificity, linearity, accuracy, precision, robustness, and sensitivity. Stressed degradation studies under acid, base, oxidative, thermal, and photolytic conditions were performed.

Results: EMP and METO exhibited Rf values of 0.54 and 0.26, respectively. Linearity was observed over 100-600 ng/band for EMP (r² = 0.9987) and 500-3000 ng/band for METO (r² = 0.9998). Recovery ranged from 99.54-101.21% (EMP) and 98.23-100.73% (METO). LOD/LOQ values were 24.67/74.76 ng/band (EMP) and 45.29/137.25 ng/band (METO). The method demonstrated precision in both intraday (EMP-8738.68 ± 80.86 and METO- 4510.93 ± 27.61) and interday (EMP-8744.97 ± 131.91 and MET0-4492.87 ± 32.53) analyses and repeatability, with the %RSD of the peak area remaining below 2%. The stressed degradation conditions were optimized to induce degradation ranging from 5% to 20%.

Conclusion: The validated HPTLC method is precise, accurate, and stability-indicating, making it suitable for routine quality control and stability testing of EMP-METO bilayer tablets.

Lyophilization is the preferred method to stabilize labile protein formulations in order to attain longer shelf life. Thus, the understanding of different parameters of lyophilization along with inherent properties of plasma protein formulations is very essential to achieve improved stability.

Objective: The present study aims to optimize the lyophilization cycle of one of the plasma proteins, Alpha-1 proteinase inhibitor (A1PI) to obtain a homogeneous and consistent cake structure using different lyophilization cycle parameters: slow freezing, fast freezing, and fast freezing with annealing.

Methods: Process analytical technology (PAT) tools like product probe temperature, Lyo Rx, LyoLogplus software were implemented for continuous lyophilization cycle monitoring, determination of freezing and eutectic points. Formulation parameters like fill volume and solid content were screened to study the impact on the product quality. Fast freezing with annealing demonstrated homogenized cake appearance, similar size crystals with more number of pores, optimum reconstitution time as well as moisture content. High fill volume proved to be beneficial for obtaining a homogenized cake structure.

Results: The product quality attributes demonstrated similarity with the market comparator. Desired quality attributes of A1PI freeze dried cake were achieved by optimizing lyophilization cycle parameters along with formulation parameters.

Conclusion: The understanding of different concepts of lyophilization can be utilized for the optimization of lyophilization parameters of other plasma proteins.

Objective: To develop ionically cross-linked pH-responsive interpenetrating polysaccharide network hydrogel tablets for the colon-targeted delivery of budesonide (BUD).

Context: The pH-responsive behaviour ensures protection of the drug during its transit through the stomach and small intestine, limiting drug release to less than 10% over a 5 h period.

Methods: We developed a series of BUD loaded pH-responsive single network and interpenetrating double network hydrogel tablets using natural polysaccharides cross-linked with Ca²⁺ ions.

Results: Both the single network hydrogel and the interpenetrating polymer network (IPN) double network hydrogel were unable to restrict drug release during the initial 5 h transit through the gastrointestinal tract (GIT). An important finding of the study was that the semi-interpenetrating polymer network (semi-IPN) hydrogel matrix tablets exhibited acceptable swelling, erosion, and drug release profiles compared to the single network and IPN hydrogels. The optimized semi-IPN hydrogel matrix tablets, prepared with equal amounts of guar gum (GG) and carboxymethyl cellulose (CMC) cross-linked with calcium ions, exhibited no drug release within the first 4 h, and only a small amount of drug of about 9% was released after 5 h of the dissolution study.

Conclusion: This semi-IPN hydrogel matrix was found to be suitable for the effective colon-specific delivery of the hydrophobic drug BUD.

Introduction: Valrubicin (VAL) is an N-trifluoroacetyl 14-valerate derivative of the anthracycline doxorubicin (DOX)and is known to have anti-tumor activity. Unfortunately, itis characterized by low solubility and instability in aqueous solutions, which hampers its applications and reduces its therapeutic efficacy.

Objective: To address this limitation, different types of cucurbiturils (CBs) were employed to explore VAL-CB complexation to enhance VAL's physicochemical characteristics in aqueous solutions.

Methods: Complexes were prepared and characterized using entrapment efficiency (EE %). UV-Vis spectroscopic titration, molecular dynamics (MD), and quantum mechanics (QM) simulations were used to predict binding interactions. In vitro release studies assessed drug release, while stability in water-based solutions was analyzed at 4, 25, and 50 °C.

Results: VAL formed stable host-guest complexes within CB in 1:1 stoichiometry, with a binding affinity of (6.29 ± 0.32 × 10³M^-1) and (2.02 ± 0.11 × 10⁴ M^-1), respectively. Additionally, molecular modeling supported a partial inclusion of the VAL structure in the CB cavity. The VAL-CB complex exhibited a 220,000-fold solubility increase, enhanced stability, and a sustained release profile.

Conclusion: The CB-VAL complex significantly enhanced physicochemical properties of VAL in aqueous solutions, with superiority for CB8. These results highlight the potential of CB7 and CB8 as novel drug delivery systems for hydrophobic drugs, offering a strategy to overcome the limitations of existing solubilization approaches in cancer therapy.

Objective: To establish an in vitro release (IVR) method for butenafine hydrochloride cream using Immersion Cells and compare the drug release characteristics of commercial samples.

Significance: Reevaluating post-listing semisolid drug products based on quality attributes of IVR performance is crucial for guaranteeing clinical efficacy.

Methods: An in vitro release testing (IVRT) method using Immersion Cells was developed and validated for sensitivity, linearity, and reproducibility. It was adapted for use with Vertical Diffusion Cells (VDCs) to compare two devices. Univariate tests were conducted to assess the effect of excipients on in vitro release rates (IVRRs). Three regulatory guidelines recommended by FDA, NMPA and EMA for IVR performance consistency assessment were compared to evaluate the sameness of marketed samples.

Results: For IVRT of butenafine hydrochloride cream, Immersion Cells exhibited the same functionality as VDCs. Stearyl alcohol which serves as oil phase matrix and thickener in the cream had a significant impact on IVRRs. Regarding the consistency of marketed samples, FDA guidelines supported a consistent conclusion, while NMPA and EMA guidelines reached the opposite conclusion, which were primarily attributed to different acceptance criteria outlined in the three regulatory guidelines.

Conclusions: Additional strategies are needed to ensure consistent therapeutic outcomes of butenafine hydrochloride cream throughout its life cycles, such as stricter control of stearyl alcohol dosage during manufacturing. Further research is needed to explore appropriate limits for consistency assessment of it. Immersion Cells offers the advantage of lower cost in routine quality control and its application in IVRT for semisolid formulations merits further expansion.

Objective: To provide a comprehensive overview of recent advancements in transdermal drug delivery systems (TDDSs), with a focus on their design, development, evaluation, and therapeutic importance.

Significance of review: TDDSs offer a noninvasive route of drug administration that bypasses gastrointestinal metabolism, enhances patient compliance, and improves pharmacokinetic profiles. Over the past two decades, their role in controlled drug delivery has increased significantly.

Key findings: This review traces the evolution of TDDSs from first-generation systems to modern formulations, highlighting key properties such as drug lipophilicity, molecular size, optimal pH, and potential for skin irritation. Major formulation strategies-membrane permeation, matrix diffusion, and microreservoir systems-are discussed. Testing methodologies, including physicochemical characterization, in vitro diffusion studies, and in vivo evaluations, have also been explored. Advancements in TDDSs have led to the development of more effective transdermal patches capable of increasing skin permeability and expanding the range of drugs that can be delivered. Despite limitations such as difficulty in delivering large- or high-dose molecules, TDDSs demonstrate improved therapeutic efficiency and better patient adherence.

Conclusions: TDDSs represent a significant innovation in drug delivery, offering several advantages over conventional routes. The ongoing development of these materials holds promise for broader clinical applications and improved therapeutic outcomes.

Objective: Silver nanoparticles (AgNPs) are widely utilized in anti-migratory applications due to their beneficial physicochemical and biological properties. This study aimed to evaluate the in vitro cytotoxic and anti-migratory effects of AgNPs synthesized using the above-ground parts (stems, flowers, and leaves) of Onosma mutabilis (O. mutabilis).

Significance: Green-synthesized AgNPs derived from O. mutabilis exhibit notable cytotoxic and anti-migratory effects on A549 cells, offering dual-functional potential. Their biocompatibility and capacity for targeted release in acidic tumor microenvironments make them promising candidates for sustainable cancer therapies.

Methods: AgNPs were green-synthesized using aqueous plant extracts and characterized by ultraviolet-visible spectroscopy (UV-Vis spectroscopy), X-ray diffraction (XRD), fourier transform infrared (FTIR), and scanning electron microscopy (SEM). Cytotoxicity against A549 cells was assessed via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and anti-migratory effects were examined using a scratch assay.

Results: UV-Vis spectroscopy confirmed the formation of AgNPs synthesized from O. mutabilis extracts by showing a characteristic absorption band around 420-480 nm. XRD analysis revealed their crystalline structure, while SEM demonstrated predominantly spherical morphology. MTT assay indicated that the AgNPs, especially those derived from the flower extract, significantly reduced A549 cell viability in a dose- and time-dependent manner, with an IC₅₀ value of 5.28 µg/mL. In addition, wound healing assays confirmed their strong anti-migratory activity.

Conclusion: These findings suggest that green-synthesized AgNPs induce cytotoxic and anti-migratory effects, highlighting their potential as therapeutic agents against A549 lung cancer cells.