Journal of pharmaceutical sciences最新文献

{"title":"Synthesis, characterization and physicochemical properties of ofloxacin in cocrystal form with nicotinic acid in aqueous and beta-cyclodextrin solutions.","authors":"Anita Ghobadian, Raha Kaviani, Ali Shayanfar","doi":"10.1016/j.xphs.2025.104027","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104027","url":null,"abstract":"<p><p>Ofloxacin (racemic form) and its L-isomer, levofloxacin, are fluoroquinolone-class antibiotics, effective against a wide range of microorganisms. Due to ofloxacin's low water solubility, various methods, such as cosolvency and the formation of new crystalline forms, including salts or cocrystals, have been employed to enhance its solubility. In this study, we aimed to prepare and characterize a novel ofloxacin-nicotinic acid cocrystal, evaluate its solubility in the presence of various concentrations of β-cyclodextrin (βCD), and synthesize a levofloxacin-nicotinic acid cocrystal followed by thermodynamic solubility analysis. The cocrystal of ofloxacin and nicotinic acid was prepared by solvent evaporation technique in a 1:1 molar ratio. Powder X-ray diffraction (PXRD) analysis and Differential Scanning Calorimetry (DSC) data were used to characterize the prepared cocrystals. The thermodynamic solubility of ofloxacin, levofloxacin, the coformers, and ofloxacin cocrystals was determined in water and βCD solutions. In general, cocrystallization of ofloxacin and levofloxacin with nicotinic acid improved their aqueous solubility, and this increase is more considerable for the racemic form. Increasing concentrations of βCD slightly decreased the thermodynamic solubility but improved the solution stability of the ofloxacin cocrystal. Cocrystallization and βCD had a noticeable effect on the physicochemical properties of ofloxacin, nicotinic acid and their cocrystal form.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104027"},"PeriodicalIF":3.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Monte Carlo simulation-based Approach to Define the Target Fill Volume and Stopper Insertion Depth for Manufacturing Pre-filled Syringe Combination Products.","authors":"Robert Kuo, Kavin Kowsari, Kaitlin Wang, Brian Wong, Ivy Birkhold, Wail Rasheed, Peng Li, Guangli Hu","doi":"10.1016/j.xphs.2025.104024","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104024","url":null,"abstract":"<p><p>Fill volume and stopper insertion depth are important parameters that require definition and de-risking prior to commercial-scale manufacture of pre-filled syringe combination products. Due to cost and time constraints, it is not practical to conduct extensive development runs in the manufacturing facility to optimize and validate process parameter settings. In response to this need, we used Monte Carlo simulations to predict the outcome variability by modeling input parameters using their expected statistical distributions. Governing equations were developed for the desired outcomes of deliverable volume and air gap size. Input variables included sterile barrier height, frictional force, and syringe and stopper dimensions, for which the values were determined either by laboratory measurement, specifications provided by vendors, or conservative assumptions representing worst-case scenarios. Results from these simulations were used to set the target values and tolerance ranges for both fill volume and stopper insertion depth to maximize the probability that manufactured PFS batches would meet acceptable criteria for deliverable volume and sterility.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104024"},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genistein-loaded nanostructured lipid carriers for intranasal brain delivery: Preparation, optimization, in-vitro evaluation, and amelioration of bioavailability.","authors":"Nabil K Alruwaili, Ameeduzzafar Zafar, Omar Awad Alsaidan, Mohd Yasir, Lubhan Singh, Mohammad Khalid, Md Ali Mujtaba, Dibya Sundar Panda","doi":"10.1016/j.xphs.2025.104025","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104025","url":null,"abstract":"<p><p>Genistein (GN) is a natural isoflavonoid phytoestrogen found in soybeans. It has various drawbacks, like poor solubility, high metabolism, and low oral bioavailability. This research work aimed to develop GN-loaded nanostructured lipid carriers (NLCs) for intranasal administration. The NLCs were developed by the emulsification homogenization technique and optimized by the Box Behnken design (BBD) using expert design software. The optimized formulation (GNNLCs13) has 215.6 ± 9.13 nm PS, 0.335 PDI, and -38.1mV zeta potential. The optimized formulation showed high entrapment efficiency of GN (82.25 %) and sustained release profile (80.0 ± 3.01 % in 24 h). The FTIR study showed no interaction between GN and excipients. The X-ray diffraction (XRD) study showed the amorphization of GN into the GNNLCs matrix. The optimized GNNLCs exhibited significantly higher flux and apparent permeability coefficient (1.785 µg/cm²/h and 1.785 × 10⁻³ cm/h) than pure GN-dispersion (6.377 µg/cm²/h and 6.377 × 10⁻³ cm/h). The relative bioavailability of optimized GNNLCs administered intranasally was 277.39 % higher than optimized GNNLCs orally and 414.04 % higher than intranasal GN-dispersion. The drug targeting potential (DTP) of intranasally optimized GNNLCs was significantly higher (66.0%) than that of intranasal GN-dispersion (25.87%). Similarly, drug targeting efficiency (DTE) of optimized GNNLCs in the brain was also determined and was significantly higher (294.05 %) compared to GN-dispersion (134.90 %) administered intranasally. From the outcomes, it can be established that NLCs are a promising novel carrier for intranasal brain delivery of GN with enhanced bioavailability and neuroprotective action.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104025"},"PeriodicalIF":3.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Empagliflozin.","authors":"Reiji Negoya, Mayuki Tsueoka, Xichen Sun, Shuto Nishida, Bertil Abrahamsson, Naseem A Charoo, Rodrigo Cristofoletti, Peter Langguth, Mehul Mehta, Alan Parr, James E Polli, Vinod P Shah, Jennifer Dressman, Atsushi Kambayashi","doi":"10.1016/j.xphs.2025.104023","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104023","url":null,"abstract":"<p><p>The objective of this monograph is to assess the applicability of the BCS-based biowaiver for empagliflozin, a sodium glucose co-transporter (SGLT2) inhibitor indicated for the oral management of Type 2 diabetes mellitus. In this assessment, published evidence on membrane permeability, solubility, and formulation performance was examined to determine whether the BCS-based biowaiver can be applied. Empagliflozin is highly soluble but not highly permeable. Therefore, it was concluded that empagliflozin is a BCS class III drug. In cases where a test formulation has a formulation similar to that of the innovator product (Jardiance) and both formulations show very rapid dissolution with 85% or more in 15 minutes, immediate-release solid oral formulation containing empagliflozin are eligible for a waiver of clinical studies. The ability to apply the biowaiver concept to empagliflozin, as proposed in this monograph, would contribute to the streamlined approval of generic versions of this essential medicine around the world.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104023"},"PeriodicalIF":3.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A self-assembled nanocomplex from starch-protein- fatty acid: Thermodynamics of self-assembly.","authors":"Deepak Bhopatkar, Bruce R Hamaker, Nawel Khalef, Aziz Bakri, Osvaldo H Campanella","doi":"10.1016/j.xphs.2025.104018","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104018","url":null,"abstract":"<p><p>A self-assembling, nanoscale complex formed from common biological molecules, starch, proteins, and fatty acids, was previously reported by our group. While the formation of this nanocomplex has been confirmed using various analytical techniques, its thermodynamic distinctiveness compared to conventional nano-emulsion systems has not yet been explored. This study aims to provide a physicochemical understanding of the self-assembly process by evaluating changes in thermodynamic properties, enthalpy, entropy, and the Gibbs free energy during complex formation. Interactions among these biological molecules, mixed in specific ratios, were monitored using modulated differential scanning calorimetry (MDSC). Changes in the reversing heat capacity during the initial cooling cycle were used to calculate the entropic and the Gibbs free energy changes associated with self-assembly. Applying classical equilibrium thermodynamics, it was demonstrated that the presence of protein thermodynamically favored the formation of a higher-order nanostructure, distinguishing it from typical emulsion systems. Moreover, this structure is more stable than binary complexes such as amylose-fatty acid and protein-fatty acid assemblies. Our findings provide compelling evidence that these self-assembling nanoscale complexes are not only chemically viable but also thermodynamically favored and stable.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104018"},"PeriodicalIF":3.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-obesity effects of novel Topiramate-Ferulic acid conjugate nanocrystals in high-fat diet-induced obese C57BL6/J mice.","authors":"Ipsa Padhy, Biswajit Banerjee, Biswakanth Kar, Sujata Mohapatra, Tripti Sharma","doi":"10.1016/j.xphs.2025.104022","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104022","url":null,"abstract":"<p><p>Curbing the enzymatic action of human pancreatic lipase has emerged as an effective strategy for designing and developing anti-obesity medications. We reported the 2D QSAR based design, synthesis and biological evaluation of novel Topiramate-phenolic acid conjugates in our previous work. Among the synthesized conjugates, T4 displayed potent pancreatic lipase inhibition as well as antioxidant property. Although, low aqueous solubility of T4 raised concerns regarding its further development into an orally active antiobesity drug candidate. To address the poor water solubility and hence to alleviate bioavailiblity concerns, in the current study we focused on the fabrication of nanocrystals of pure conjugate T4. The fabricated nanocrystals were characterised by FTIR, XRD, DSC, SEM along with particle size analysis. Further, tin vitro dissolution was carried out to study he drug release pattern in PBS (pH 6.8). The anti-obesity effect of T4NC was investigated in HFD-induced obese male C57BL6/J mice model in a 14-week study period. A reduction in crystalline nature of T4NC nanocrystals was evident from the PXRD and DSC analysis. The nanocrystals displayed enhanced dissolution as depicted by about 75% cumulative drug release in contrast to only 39% cumulative drug release from the parent conjugate. Administration of T4NC nanocrystals in HFD induced obese mice reduced increased body weight, feed intake, food efficiency ratio and organ weights. Elevated levels of serum TG, TC, LDL-C, AST and ALT were reduced to normal, while reduced HDL-C levels were improved in T4NC treated mice. T4NC nanocrystals administration in obese mice also ameliorated high fat diet induced insulin resistance as observed from the HOMA-IR values. High lipid percentage in fecal matter of mice treated with T4NC indicated decreased catalytic activity of pancreatic lipase leading to reduced dietary lipid digestion and absorption. Furthermore, gene expression studies revealed the inhibitory effect of T4NC on adipocyte differentiation via downregulating PPARγ expression. The antiobesity effects of T4NC nanocrystals were significantly higher (p < 0.05) than the conventional lipase inhibitor orlistat. Conclusively, the results of the study warranty the development of novel T4NC nanocrystals as potential antiobesity medication.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104022"},"PeriodicalIF":3.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of synergistic effects of β-defensin, vesatolimod and resiquimod in increasing the potency of a therapeutic HIV-1 vaccine candidate.","authors":"Seyedeh Somayeh Hosseini Alarzi, Azam Bolhassani, Elnaz Agi, Reza Nekouian","doi":"10.1016/j.xphs.2025.104019","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104019","url":null,"abstract":"<p><p>Improvement of therapeutic vaccination strategies is critical to control the human immunodeficiency virus-1 (HIV-1) infection. The goal of this study is to determine the immunostimulatory effects of toll-like receptor (TLR) agonists including β-defensin (TLR4 agonist), vesatolimod (GS-9620: TLR7 agonist) and resiquimod (R848: TLR7/8 agonist) as individual or combined with the Nef^mut-Tat antigen candidate in BALB/c mice. The results of immune responses for groups receiving the recombinant Nef^mut-Tat protein (∼ 35 kDa) and the recombinant β-defensin-Nef^mut-Tat protein (∼ 45 kDa) showed that the linkage of β-defensin to Nef^mut-Tat protein could significantly increase the secretion of IFN-γ, TNF-α and Granzyme B. Furthermore, the highest levels of IFN-γ, TNF-α and Granzyme B was observed in group receiving β-defensin-Nef^mut-Tat protein + GS-9620 + R848 regimen indicating the potent synergistic effects of TLR agonists on induction of cellular immunity (i.e., stimulation of T-helper 1 cells and cytotoxic T lymphocytes). This regimen could significantly induce IFN-γ and TNF-α in splenocytes infected with single-cycle replicable (SCR) HIV-1 in vitro, as well. It was interesting that no significant differences in TNF-α and Granzyme B secretion were observed between groups receiving β-defensin-Nef^mut-Tat protein + GS-9620 and β-defensin-Nef^mut-Tat protein + R848; although group receiving β-defensin-Nef^mut-Tat protein + R848 could significantly induce IFN-γ secretion in uninfected and infected splenocytes compared to group receiving β-defensin-Nef^mut-Tat protein + GS-9620. These findings demonstrated that the simultaneous use of TLR 4, 7 and 8 agonists could improve and maintain cellular immunity against SCR HIV-1 infection suggesting an effective approach for eradication of latent HIV reservoir.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104019"},"PeriodicalIF":3.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Law of Static Solute Transport in Degenerated Cartilage.","authors":"Lilan Gao, Heng Liu, Weichao Dai, Jie Liu, Jiayu Wu, Chunqiu Zhang","doi":"10.1016/j.xphs.2025.104020","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104020","url":null,"abstract":"<p><p>Results indicate that mass transport within cartilage exhibits pronounced anisotropy along the surface pathway, with molecular concentrations showing significant gradients across cartilage thickness and effective diffusion coefficients decreasing sharply from superficial to deep layers. The effective diffusion coefficients in all cartilage layers decrease by more than 50% as molecular weight increases from 400 Dalton to 150 kDa. The larger molecules (LMT) exhibit lower diffusivity than smaller ones (SMT) across all layers. In the side pathway, molecular concentrations remained nearly constant between superficial, intermediate, and deep layers, forming gradients primarily along the width (i.e., diffusion direction), indicating minimal influence of interlayer structure on diffusion behavior. In the composite pathway, mass transfer patterns resembled the surface pathway, with clear concentration gradients forming along the thickness while maintaining uniformity across the width, demonstrating significant differences in transport efficiency among the different molecules. It was also demonstrated that cartilage degeneration significantly enhances the transport efficiency of solutes across all molecular weight ranges when diffused via the composite patrway. The results provides valuable references for optimizing OA drug delivery systems and enhancing intra-articular drug retention time.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104020"},"PeriodicalIF":3.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the impact of excipient variability on oral solid dosage form performance: a possible role for multivariate data analysis, in the form of principal component analysis.","authors":"Pauline H M Janssen, Bastiaan H J Dickhoff, Ana Ferreira, John Gamble, Rachael Shinebaum, Mike Tobyn","doi":"10.1016/j.xphs.2025.104021","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104021","url":null,"abstract":"<p><p>The development of a robust oral solid dosage form requires knowledge of all the sources of variation that could impact the dosage form's performance and stability. One of those sources of variability is in the excipients that can make up the bulk of the dosage form. Raw material and manufacturing variability can make a difference to the physical properties and performance of the excipient. It is, however, also important to note that sources of variation in data include analytical and sampling variation, which affect the reported data without directly impacting the performance of the dosage form. Working closely with an excipient supplier, drug product manufacturers can substantially improve their understanding of the sources of variability in the excipients that they use. This helps to strengthen the regulatory design space for their asset and will helps stabilise the product during its commercial life cycle. The use of multivariate analysis to examine reported data, along with targeted experimentation, is a demonstrated way to work towards this goal. In this paper we give examples of how this can be achieved.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104021"},"PeriodicalIF":3.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Hydrodynamic, Mechanical, and Interfacial Stress during Downstream Processing on Adeno-Associated Virus Serotype 8 and 9.","authors":"Angela Picciano, Kelly Wilson, Katherine Joyner, Michaela Wendeler","doi":"10.1016/j.xphs.2025.104017","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.104017","url":null,"abstract":"<p><p>Adeno-associated virus (AAV) is now well established as one of the most promising delivery vectors for gene therapy. During the manufacturing process, solutions of AAV are exposed to hydrodynamic and mechanical forces, and their impact on AAV integrity and product quality are still poorly understood. In this work, we studied the effects of different physical stress factors encountered during bioprocessing, including pumping, extensional flow, cavitation, mechanical stress, air-liquid interfaces, and high shear rates on two of the most employed serotypes, AAV8 and AAV9. The influence of stress factors was assessed in scale-down models, and the impact was determined by measuring soluble AAV concentration in solution, full-to-total capsid ratio, AAV aggregation and fragmentation, capsid molecular weight, capsid size, particle content, and thermal stability. Our data demonstrate that significant losses of soluble AAV occur through all operations that included pumping, and this effect was more pronounced for AAV8. This serotype also showed higher propensity for particle formation in response to the physical strains. None of the stresses resulted in the appearance of size or weight variants of soluble AAV, and no effect on capsid thermal stability or temperature of aggregation onset was observed. In addition, no changes in full-to-total capsid ratio were detected. Remarkably, both AAV8 and AAV9 experienced little impact and no reduction in titer when exposed to isolated high shear rates (20,000 s^-1). This illustrates the stability of AAV viral vectors towards shear forces but highlights the need to carefully optimize parameters for pumping operations to enhance performance and ensure consistency during AAV bioprocessing.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104017"},"PeriodicalIF":3.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}