Drug Development and Industrial Pharmacy最新文献

Objective: Periodontitis, characterized by chronic gingival inflammation driven by polymicrobial biofilm formation, presents a significant therapeutic challenge due to the inherent difficulty of antimicrobial penetration through the biofilm matrix and limited drug retention.

Methods: To address these challenges, this study developed a metronidazole-loaded spanlastic-based mucoadhesive hydrogel (MTZ-SPLG) for direct intra-pocket delivery, designed to overcome biofilm barriers and prolong drug residence time. The spanlastics (SPL) formulation achieved optimal characteristics (93% EE, 0.168 PDI, 280.8 nm size) through Design Expert^® 13 optimization, utilizing Span 80 (15 mg/ml) and Tween 80 (6.5 mg/ml) with 4-min sonication in the ethanol injection process. FTIR analysis confirmed the absence of chemical interactions, while DSC and XRD demonstrated successful transformation of metronidazole (MTZ) from crystalline to amorphous form. The optimized metronidazole loaded spanlastics (MTZ-SPL) incorporated into a Carbopol^® hydrogel base, exhibited suitable intra-periodontal properties including homogeneity, appropriate pH, and optimal spreadability, with mucoadhesive strength of 2256.3 N/m².

Results: In vitro studies at pH 6.8 revealed sustained drug release following Korsmeyer-Peppas model with Fickian diffusion, outperforming conventional MTZ formulations. The MTZ-SPLG formulation demonstrated superior antibacterial efficacy with the largest inhibition zones (29.0-30.5 mm), lowest MIC values (2.2-5.9 μg/mL), and highest biofilm inhibition (60-89%) and degradation (43.6-64.3%) across all tested pathogens. Despite lower permeation than MTZ-SPL, MTZ-SPLG achieved optimal tissue retention (81.6 μg/cm²).

Conclusions: Based on our study findings, the formulation significantly reduced inflammation and demonstrated superior efficacy in periodontitis treatment.

Objective: The primary aim of the study is to highlight the application of Quality by Design (QbD) in the formulation of parenterals, with a focus on academic and industrial aspects.

Significance: Parenteral formulations, particularly those administered intravenously, provide substantial therapeutic benefits and 100% bioavailability. However, problems like drug solubility, stability, sterility, and manufacturing viability hinder their development. By methodically tackling these issues, QbD helps guarantee consistent patient safety and product quality, while minimizing wastage of time and resources.

Methods: This review was carried out by focusing on the implementation of ICH Q8-Q10 guidelines and QbD frameworks to parenteral drug development, while emphasizing tools such as critical process parameters (CPPs), critical quality attributes (CQAs), design of experiments (DoE), and process analytical technology (PAT). To illustrate real-world applications, case studies from academia and industries were additionally examined.

Key findings: The study demonstrates how QbD enables robust parenteral formulations by facilitating a thorough understanding and control of both formulation and process factors. QbD implementation, as shown in the case studies, improved formulation robustness, risk mitigation, regulatory compliance, and lifecycle management.

Conclusion: The review concludes that QbD implementations in parenteral formulation increase the quality of the product. It also states that the safety of parenteral products can be ensured by considering factors such as contamination, particle size, osmolarity, and others when designing the formulation.

Objective: This study aimed to develop and characterize orodispersible tablets (ODTs) containing solidagenone (SLG), a bioactive constituent of Solidago chilensis Meyen with described anti-inflammatory properties and potential relevance to asthma management.

Significance: ODTs offer advantages for patients with swallowing difficulties and may improve adherence in chronic respiratory conditions.

Methods: SLG underwent physicochemical and solid-state characterization (FTIR, particle size, SEM morphology, XRPD, DSC, and TGA). Two SLG-loaded ODT formulations (3 mg) and their respective placebos were produced by direct compression and assessed for weight uniformity, hardness, friability, diameter, thickness, disintegration time, and SLG content.

Results: SLG exhibited a predominantly crystalline hexagonal-pyramidal morphology and thermal stability up to approximately 190 °C. All ODT formulations complied with the friability specifications of the Brazilian Pharmacopeia, 6th edition (≤1%), with hardness values ranging from approximately 40-60 N. SLG-loaded tablets demonstrated fast disintegration (12.6 ± 2.6-17.0 ± 4.0 s), with the optimized formulation meeting both European Pharmacopeia (≤180 s) and FDA/USP (<30 s) criteria for ODTs. Chromatographic analysis confirmed SLG content and integrity in the optimized formulation.

Conclusion: These results support SLG as a promising candidate for orodispersible tablet formulation development, encouraging further pharmacodynamic and clinical studies to explore its potential application in asthma management.

Objective: Rosuvastatin has been used to treat hyperlipidemia commercially by reducing triglycerides, apolipoproteins, and low-density lipoproteins, increasing high-density lipoproteins, and decreasing triglycerides.

Significance: However, it is a BCS class II drug and has the problems of low aqueous solubility and low bioavailability. The cocrystal approach has been repeatedly used to improve the solubility of poorly soluble drugs, with potential to enhance other physicochemical properties. The cocrystal approach also shows a high degree of dependence on the manufacturing methods used to produce the same.

Methods: In this study, cocrystals of Rosuvastatin calcium have been synthesized using the amino acid coformers L-Glutamine and L-Asparagine. These cocrystals have been produced using two separate manufacturing techniques: spray drying and solvent evaporation.

Results: Solubility studies were used to identify the manufacturing technique with better solubility parameters. The spray-drying approach showed a clear improvement in solubility compared to the solvent evaporation method, with cocrystals of Rosuvastatin:L-Asparagine showing a 4.95-fold increase in solubility, the highest observed. Solid-state characterization, such as Fourier-Transform Infrared spectroscopy, Differential Scanning calorimetry, and Powder X-Ray Diffraction, was performed on the shortlisted cocrystals, and dissolution studies were conducted to quantify the solubility enhancement observed upon cocrystallisation.

Conclusions: This study demonstrated that different manufacturing techniques significantly affect the solubility of rosuvastatin cocrystals. Cocrystals synthesized using two distinct coformers and methods showed notable differences, with spray drying producing superior cocrystals. These spray-dried cocrystals offer advantages for scaling up into continuous manufacturing suitable for industrial production.

Objective: This study evaluated the hydrolytic behavior of dodecyl nicotinate under chemical and biological conditions to determine its suitability as a controlled-release prodrug of niacin.

Significance: Niacin therapy is limited by a short half-life and dose-dependent flushing, which compromise adherence despite its lipid-modifying benefits. Prodrug design provides a strategy to enhance stability, prolong release, and facilitate enzymatic activation. Dodecyl nicotinate, a lipophilic C12 ester of niacin, is expected to balance membrane permeability with enzymatic lability. While shorter (octyl) and longer (myristyl) analogs have been examined, systematic kinetic data for the C12 ester remain scarce. This study provides new insights into its stability and enzymatic conversion, highlighting translational potential for oral and transdermal controlled-release systems.

Methods: Hydrolysis kinetics were investigated in buffered aqueous media (pH 5-10) at 80 °C using HPLC. Pseudo-first-order rate constants and pH-rate profiles were derived, and buffer catalysis was assessed in phosphate, borate, and carbonate systems. Enzymatic hydrolysis was studied in rat liver and skin homogenates at 37 °C, with Michaelis-Menten modeling applied to characterize kinetics.

Results: Dodecyl nicotinate showed pH-dependent pseudo-first-order hydrolysis, with carbonate buffer exerting the greatest catalytic effect. Enzymatic cleavage was markedly faster than chemical hydrolysis, with half-lives of 24.8 min in liver and 63 min in skin homogenates. Michaelis-Menten analysis confirmed saturable enzyme kinetics.

Conclusions: Dodecyl nicotinate combines chemical stability with efficient tissue-mediated bioconversion, supporting its promise as a controlled-release niacin prodrug suitable for both oral and transdermal delivery.

Objective: To enhance the dermal delivery and therapeutic potential of psoralen from Psoralea corylifolia in psoriasis through phytosomal encapsulation.

Significance: Psoriasis is a chronic inflammatory skin disorder affecting 2-4% of the Western population, characterized by abnormal keratinocyte proliferation and immune system dysregulation. Conventional treatments are limited by their side effects and poor adherence. Psoralen shows anti-psoriatic activity, but its therapeutic use is limited by poor dermal penetration and low bioavailability; enhancing its solubility and skin permeation could potentially improve its local effectiveness. To our knowledge, this is the first report of psoralen encapsulation into phytosomes and the first comparative evaluation of soya lecithin (SL) vs. egg lecithin (EL) as phospholipid carriers for psoralen dermal delivery.

Methods: Psoralen-loaded phytosomes were prepared using the thin-film hydration method, with SL or EL. A Box-Behnken Design (a response surface methodology) was used to optimize formulation variables (X1: psoralen extract: soya/egg lecithin w/w, X2: psoralen extract: cholesterol w/w, and X3: reaction temperature °C) and responses (Y1: entrapment efficiency % and Y2: particle size nm). Optimized formulations were characterized for particle size, PDI, entrapment efficiency (EE%), loading capacity, zeta potential, drug content, FTIR, DSC, and in-vitro release.

Results: SL-based phytosomes (PPST5) exhibited a small mean particle size (≈ 140.2 ± 2.8 nm) and higher entrapment efficiency (≈ 90.89 ± 0.82%), compared to EL-based phytosomes (PPET2). Both formulations demonstrated acceptable colloidal stability (zeta potential > |22 mV|) and high drug content. In vitro release studies showed that SL-based phytosomes provided sustained and significantly higher psoralen release (98.98 ± 1.31%) in 24h compared to the psoralen suspension (63.15 ± 13.48%) and EL-based phytosomes (88.54 ± 2.04%). FTIR and DSC data are consistent with psoralen-phospholipid interactions/complexation. Statistical analysis (ANOVA) showed that lecithin type and phospholipid:drug ratio significantly affected formulation performance (see Table X, ANOVA in Supplementary Table S1).

Conclusions: SL-based phytosomes improved psoralen dermal delivery by enhancing entrapment, penetration, and providing sustained release. These findings support phytosomal encapsulation as a promising topical delivery strategy for psoralen; however, direct bioavailability and in vivo/ex vivo validation are required to confirm therapeutic efficacy in psoriasis.

Objective: Molecular motors are nanoscale devices capable of converting chemical, light, or magnetic energy into mechanical motion. This review aims to provide a comprehensive overview of recent advancements in molecular motor technology, with a specific focus on their applications in cargo transport and drug delivery systems. It systematically examines both biomolecular and artificial molecular motors, emphasizing the regulatory mechanisms governing their operation.

Significance of the review: Traditional drug delivery systems often suffer from low bioavailability, poor targeting, and uncontrollable release. Molecular motors are renowned for their ability to convert various energy forms into mechanical motion, making them highly promising for biomedical applications such as biosensing, anticancer therapy, drug delivery, and diagnostics. Through comparative analysis of natural and artificial systems, this review highlights how energy conversion mechanisms and motion control strategies can enhance the efficacy, specificity, and safety of drug delivery.

Key findings: The review discusses recent progress in molecular motor design and function, particularly in cargo transport and targeted drug delivery. It analyzes the advantages of these systems, such as precise control and efficient energy conversion, while also addressing current challenges, including scalability and biocompatibility.

Conclusion: Despite remarkable advances, several critical bottlenecks persist, including scalability, material toxicity, and controllability in physiological environments. Molecular motors with tunable motion control and adaptive regulation hold significant potential for advancing drug delivery and biomedical applications.

Nanoformulated androgen receptor (AR) antagonists constitute a cutting-edge advancement in the treatment of AR-driven cancers by significantly enhancing the precision and effectiveness of therapy. These nanoparticle-based formulations are uniquely designed to simultaneously inhibit AR-driven transcription and critical signaling pathways involved in tumor progression and drug resistance, including PI3K/AKT and MAPK cascades. The distinctive properties of nanoparticles, such as improved bioavailability, controlled and sustained drug release, and active tumor targeting, enable these AR antagonists to achieve higher intratumoral concentrations and minimize off-target effects. This targeted delivery system not only overcomes common resistance mechanisms seen with conventional AR antagonists but also facilitates the co-delivery of multiple agents for synergistic therapeutic action. This review highlights how nanoformulated AR antagonists hold immense potential to transform cancer management by providing more effective, durable responses and a foundation for personalized, multi-pathway-targeted treatment strategies in advanced and resistant cancers. Their development addresses critical clinical challenges, offering a promising pathway to improve patient outcomes and fill significant gaps in current oncologic therapies.

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.