Journal of pharmaceutical sciences最新文献

{"title":"Clotrimazole mucoadhesive films with extended-release properties for vaginal candidiasis-A hot-melt extrusion application.","authors":"Kirti Sawant, Rasha M Elkanayati, Ahmed Almotairy, Michael A Repka, Mashan Almutairi","doi":"10.1016/j.xphs.2025.01.011","DOIUrl":"10.1016/j.xphs.2025.01.011","url":null,"abstract":"<p><p>Clotrimazole, an antifungal agent for treating vaginal candidiasis, faces challenges in localized delivery due to poor solubility, complexity of the vaginal environment, limited fluid for dissolution, and rapid self washout of the vagina. The study aimed to enhance clotrimazole solubility using hot-melt extrusion (HME) to develop vaginal films with adequate bioadhesion, mechanical strength, and extended-release properties. Different formulations were created by varying the ratios of polyethylene oxide (PEO) grades (N750 and N10) to adjust the films' properties. The films demonstrated extended-release profiles, prolonging clotrimazole release for up to eight hours, with a cumulative gradual and complete in- vitro release in 100 mL of simulated vaginal fluid with 0.5% sodium dodecyl sulfate. In contrast, the marketed vaginal ovules exhibited a rapid and complete release within 30 minutes of shell rupture. The release kinetics followed Krosmeyer-Peppas model, and zero-order release mechanism. Films containing 25% clotrimazole, 56.25% PEO N750, and 18.75% PEO N10 exhibited strength of 87.9 N, stiffness of 35 N/sec, and adhesive force of 3.85 N.mm. In conclusion, the novel clotrimazole-loaded vaginal films developed using HME technology enhanced the solubility and localized vaginal delivery of clotrimazole. The extended-release profile may reduce the dosing frequency, enhance patient adherence, and improve therapeutic outcomes.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007284","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":"M1 macrophage membrane-coated nickel-arsenic nanocomplex promoting synergistic treatment of hepatocellular carcinoma.","authors":"Shu Wang, Ye Gong, Yang Ji, Dandan Liu, Hao Pan, Weisan Pan","doi":"10.1016/j.xphs.2025.01.010","DOIUrl":"10.1016/j.xphs.2025.01.010","url":null,"abstract":"<p><p>By inducing apoptosis, promoting differentiation and reducing the migration of cancer cells, arsenic has a higher therapeutic effect and lower risk of recurrence and metastasis than conventional anticancer drugs. However, the low bioavailability and adverse side effects of arsenic hinder its application in hepatocellular carcinoma (HCC). Therefore, a M1 macrophage membrane-coated nickel-arsenic/polydopamine nanocomplex (NiAsOx@P@M) was constructed to enhance the combined antitumor effects of chemotherapy and immunotherapy. The nanocomplex consisted of a nickel-arsenic oxide core, a polydopamine (PDA) shell and a M1 macrophage membrane (MM) coating. MM endowed the nanocomplex with natural tumor homing and immune escape properties, and the nanocomplex was gradually accumulated in the tumor tissue during the internal circulation. The acid response of PDA led to its degradation in the tumor microenvironment (TME). The degradation product dopamine (DA) and MM jointly promoted tumor immunity and regulated tumor-associated macrophages (TAMs) to repolarization M1 phenotype. The nickel-arsenic oxide core dissociated in an acid environment and released arsenic, thus killing tumor cells. In summary, the nanocomplex provided a promising delivery strategy for arsenic therapy of HCC and a novel design idea for the conversion of inorganic drugs into organic preparations.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007136","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":"Representative training data sets are critical for accurate machine-learning classification of microscopy images of particles formed by lipase-catalyzed polysorbate hydrolysis.","authors":"David N Greenblott, Christopher P Calderon, Theodore W Randolph","doi":"10.1016/j.xphs.2024.12.031","DOIUrl":"10.1016/j.xphs.2024.12.031","url":null,"abstract":"<p><p>Polysorbate 20 (PS20) is commonly used as an excipient in therapeutic protein formulations. However, over the course of a therapeutic protein product's shelf life, minute amounts of co-purified host-cell lipases may cause slow hydrolysis of PS20, releasing fatty acids (FAs). These FAs may precipitate to form subvisible particles that can be detected and imaged by various techniques, e.g., flow imaging microscopy (FIM). Images of particles can then be classified using supervised convolutional neural networks (CNNs). However, CNNs should be trained on representative images of particles which, as we demonstrate in this work, may be challenging to obtain. Here, we tested several rapid techniques to create FA particles and examined whether CNNs trained on microscopy images of these rapidly formed particles could accurately classify images of particles that had been produced by kinetically slower lipase-catalyzed hydrolysis of PS20. CNNs trained on images of rapidly produced particles were less accurate in classifying images of FA particles that had been produced by enzymatic hydrolysis of PS20 than CNNs trained with images of particles generated by the same slow hydrolysis, highlighting the importance of using representative image data sets for training CNN classifiers.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007093","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":"Optimizing etodolac and quercetin loaded MSNs using taguchi design: an approach for enhancing drug loading efficiency.","authors":"Sourav Chougule, Hafiz Ahmed, Snigdha Singh, Mukta Agrawal, Ravish J Patel, Amit Alexander","doi":"10.1016/j.xphs.2024.12.026","DOIUrl":"10.1016/j.xphs.2024.12.026","url":null,"abstract":"<p><p>The application of mesoporous silica nanoparticles (MSN) as a drug carrier system got immense attention in the past few years due to their exceptional high drug loading efficiency. However, the process of drug loading is quite challenging compared to other lipid-based drug delivery systems. Hence, the MSNs using different catalysts were synthesized, and their mesoporous material characteristic was confirmed by the type IV adsorption-desorption isotherm using BET analyzer. The effect of solvent selection and other process parameters (drug to MSNs ratio, period of loading, and stirring speed) on the loading of BCS class II and IV model drugs etodolac(ETD) and quercetin(QUR) respectively were investigated with the help of Taguchi DOE. The predicted value for the highest % drug loading was close to the experimental value(19.04 ± 0.50 % and 11.40 ± 0.18 % for ETD and QUR respectively). It was interesting to note, that the solvent selection had the highest impact on the drug loading of ETD into the MSNs, whereas for QUR this parameter was insignificant. Hence reflecting that a generalized procedure for the drug loading into the MSNs cannot be followed and had to be critically studied. Also, the loading of ETD and QUR into the MSNs improved the aqueous solubility (3.08 and 2.5 folds respectively). Further the in-vitro drug release properties were evaluated for ETD and QUR from MSNs in various drug release mediums to explore their release mechanism from MSNs using in vitro drug release kinetic modelling.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007077","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":"Higher concentration of trehalose dihydrate stabilizes recombinant IgG1 under forced stress conditions.","authors":"Deepika Sarin, Debasmita Chakraborty, Shravan Sreenivasan, Avinash Mishra, Anurag S Rathore","doi":"10.1016/j.xphs.2024.12.017","DOIUrl":"https://doi.org/10.1016/j.xphs.2024.12.017","url":null,"abstract":"<p><p>Stability of complex biotherapeutics like monoclonal antibodies is paramount for their safe and efficacious use. Excipients are inactive ingredients that are added to the purified product so as to offer it a stable environment. Trehalose dihydrate is a non-reducing sugar that is commonly used as a stabilizing agent in biotherapeutic formulations under liquid and frozen states. The stabilizing effect of trehalose against aggregation in protein formulations is well known. The present study aims to offer insights into the stability effects of higher trehalose concentration (230 mM) on liquid trastuzumab under different forced stress conditions including thermal, light with and without hydrogen peroxide (H₂O₂), humidity and extraction stresses. Under thermal stress, while high molecular weight (HMW) accounted for 38.80% in the trastuzumab sample without trehalose, it was 4.89% at high trehalose concentration. Similarly, under light stress with H₂O₂, the trastuzumab sample without trehalose had >80% more HMW than at high trehalose concentration. Two other IgG1 mAbs (rituximab and bevacizumab) were also evaluated for stability at higher trehalose concentrations (230 mM). Similar to trastuzumab, stabilization was observed under thermal stress for rituximab and bevacizumab at higher trehalose concentration compared to samples without trehalose (21.90% and 29.90% HMW, respectively). Likewise, accelerated (under humidity stress) and extraction stress induced secondary and tertiary structure disruptions were reduced at higher trehalose concentration. An in-silico study between binding interactions of trehalose and trastuzumab Fab region at different concentrations depicted an increase in hydrogen bonding with trastuzumab Fab when the trehalose concentration is increased, thereby reducing aggregation. Overall, mAb stability under forced stress conditions improved significantly at higher trehalose concentrations. While higher trehalose concentration (>200 mM) is used in mAb formulations and is known to minimise aggregation under thermal stress, however, the current study aims to also explore the stability imparted under light (with H₂O₂), humidity and extraction stresses for three different mAbs and attempts to explain the underlying mechanisms via in-silico studies.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971392","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":"Pneumatic tube transport of trastuzumab in IV bags-Effect of headspace and surfactant on subvisible particle formation.","authors":"Anna Kjellström, Ida Cederwall, Clàudia Sabaté Martínez, Stanley Kwok, Florian Rosenthal, Ulla Elofsson, Mattias Paulsson, Marie Wahlgren","doi":"10.1016/j.xphs.2024.12.003","DOIUrl":"10.1016/j.xphs.2024.12.003","url":null,"abstract":"<p><p>In hospitals, IV bags can be prepared in advance for logistical and microbial safety reasons in a compounding unit and then transported to wards. Transport of protein drugs using a pneumatic tube system has been reported to result in high particle levels. In this study, pneumatic tube transport of trastuzumab in saline polyolefin bags was compared to delivery by hospital porters using an electric platform truck in an underground tunnel system. The transport was tracked using designed smart labels. Two strategies to prevent particle formation, removing headspace and adding the surfactant polysorbate 20 were evaluated. The transport by pneumatic tube had a higher level of shock and vibration than truck delivery. The total particle count measured using flow microscopy also increased more for pneumatic transport than for transport by vehicle. Removing the headspace decreased particle formation for both transports. Surfactant decreases particles over 10 µm for trastuzumab in saline IV bags but increases the total particle levels. Pneumatic tube transport of saline in polyolefin bags resulted in high particle levels and surfactant increased the total particle count. Removing headspace is a measure that can be incorporated into compounding practices to cover for inadequate surfactant levels in IV bags.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964695","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":"Analytical characterization of aberrant trisulfide bond formation in therapeutic proteins and their impact on product quality.","authors":"Jordan D Pritts, Vincent M Falkowski, Thomas G Biel, Mattias Embretsen, Baikuntha Aryal, Joseph Tillotson, Frances Namuswe, V Ashutosh Rao","doi":"10.1016/j.xphs.2024.12.028","DOIUrl":"10.1016/j.xphs.2024.12.028","url":null,"abstract":"<p><p>Post translational modifications (PTMs) of proteins play an integral role in maintaining the overall structure and function of proteins including their proper folding, binding, and potency. However, not all PTMs play a positive role in protein drugs as some can lead to product-related impurities that negatively impact protein function. One example of a PTM is trisulfide formation, which appears as a product related species in multiple biologic drug products. The impacts of trisulfide formation on protein structure, stability, potency, and safety remains under investigation. Herein, we investigated and report the impact of aberrant trisulfides on erythropoietin (EPO) and somatropin (growth hormone/GH) therapeutic proteins. Utilizing LC-MS we show that one EPO product contains measurable basal levels of trisulfide bonds in its formulation and exposure to H₂S induced aberrant trisulfides in all products investigated. We report that exposure to H₂S produces moderate effects on protein stability via thermal melting monitored by circular dichroism, protein purity utilizing size exclusion chromatography, and particle content using micro-flow imaging. No changes were observed in protein folding via circular dichroism, immunogenicity screening via a THP1-blue assay, or receptor binding activity via biolayer interferometry. Together, these data provide evidence on the effects of aberrant trisulfide formation on overall product quality.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950480","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":"Application of a UV-vis spectrometer to investigate the effect of dissolution media on the diffusivity of small molecules and proteins.","authors":"Hao Lou, Gang Hu, Xi Luan, Jill M Steinbach-Rankins, Michael J Hageman","doi":"10.1016/j.xphs.2024.09.008","DOIUrl":"10.1016/j.xphs.2024.09.008","url":null,"abstract":"<p><p>To date, the commonly used methods for diffusion coefficient measurements have some hurdles that prevent them from being widely applied in pharmaceutical laboratories. This study aimed to modify a method developed by di Cagno et al. based on the use of a UV-Vis spectrometer and apply the method to investigate the effect of dissolution media on the diffusivity of small molecules and proteins. A total of five small molecules and two proteins in different aqueous media and polymer solutions were investigated in this study. By attaching a 3D-printed cover with an open slit to a standard UV-Vis cuvette, the incident UV light could only pass through the open slit to measure the local drug concentration. During the diffusion experiment, drug molecules diffused from the cuvette bottom to the slit. According to the concentration measured as a function of time, diffusion coefficient was calculated based on Fick's law of diffusion using the analytical and numerical approaches. As a result, diffusion coefficients could be accurately measured with high reproducibility. The results also suggested that different media could affect the diffusion coefficients of small molecules by < 10% and proteins by < 15%. Since the UV-Vis spectrometer is a routine instrument, this method can potentially be employed by many pharmaceutical laboratories for diffusion coefficient measurements.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"256-264"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289712","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":"Is access to leadership roles contributing to the gender pay gap in the pharmaceutical sciences?","authors":"Adeola O Coker, Cynthia A Oksanen, Tina Morris, Kristen Kalmann","doi":"10.1016/j.xphs.2024.08.018","DOIUrl":"10.1016/j.xphs.2024.08.018","url":null,"abstract":"<p><p>Gender disparity in the pharmaceutical sciences contributes to the overall gender pay gap. The gender pay inequity is worse at later career stages. Salary data for pharmaceutical scientists has been reviewed from both the American Association of Pharmaceutical Sciences (AAPS) Salary Survey and the American Association of Colleges of Pharmacy (AACP) Pharmacy Faculty Demographics and Salaries report. We share some potential causes of the pay inequity, including implicit bias, pipeline issues, family responsibilities, and others. We suggest how organizations can put processes in place to help narrow the gender pay gap. Additionally, we share suggestions for how women must take a proactive role to ensure they reach their full potential and pay equity.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"637-640"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289716","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":"Efficient determination of critical water activity and classification of hydrate-anhydrate stability relationship.","authors":"Xin Yao, Tianyi Xiang, Shuang Chen, Busayo D Alagbe, Geoff G Z Zhang, Richard S Hong, Changquan Calvin Sun, Lian Yu, Ahmad Y Sheikh","doi":"10.1016/j.xphs.2024.06.012","DOIUrl":"10.1016/j.xphs.2024.06.012","url":null,"abstract":"<p><p>For a pair of hydrated and anhydrous crystals, the hydrate is more stable than the anhydrate when the water activity is above the critical water activity (a_wc). Conventional methods to determine a_wc are based on either hydrate-anhydrate competitive slurries at different a_w or solubilities measured at different temperatures. However, these methods are typically resource-intensive and time-consuming. Here, we present simple and complementary solution- and solid-based methods and illustrate them using carbamazepine and theophylline. In the solution-based method, a_wc can be predicted using intrinsic dissolution rate (IDR) ratio or solubility ratio of the hydrate-anhydrate pair measured at a known water activity. In the solid-based method, a_wc is predicted as a function of temperature from the dehydration temperature and enthalpy obtained by differential scanning calorimetry (DSC) near a water activity of unity. For carbamazepine and theophylline, the methods yielded a_wc values in good agreement with those from the conventional methods. By incorporating a_wc as an additional variable, the hydrate-anhydrate relationship is categorized into four classes based on their dehydration temperature (T_d) and enthalpy (ΔH_d) in analogy with the monotropy/enantiotropy classification for crystal polymorphs. In Class 1 (ΔH_d< 0 and T_d ≥ 373 K), no a_wc exists. In Class 2 (ΔH_d>0andT_d≥373K), a_wc always exists under conventional crystallization conditions. In Class 3 (ΔH_d<0andT_d<373K), a_wc exists when T>T_d. In Class 4 (ΔH_d>0andT_d<373K), a_wc exists only when T<T_d. The hydrate-anhydrate pairs of carbamazepine and theophylline belong to Class 4.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"127-135"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468874","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}