Journal of pharmaceutical sciences最新文献

{"title":"Encapsulation of synthesized purpurin-18-N-aminoimide methyl ester in lipid nanovesicles for use as agents in photodynamic cancer therapy.","authors":"Sooho Yeo, Huiqiang Wu, Young Kyu Song, Il Yoon, Woo Kyoung Lee","doi":"10.1016/j.xphs.2025.01.001","DOIUrl":"10.1016/j.xphs.2025.01.001","url":null,"abstract":"<p><p>This study aimed to synthesize purpurin-18-N-aminoimide methyl ester (P18 N AI ME) and encapsulate it into lipid nanovesicles (LNVs) for potential application as photodynamic therapy (PDT) agents in cancer therapy. PDT, a light-induced treatment, offers several advantages over conventional cancer treatments, such as minimal invasiveness and localized action. P18 N AI ME, a chlorine class photosensitizer model drug, was synthesized in an attempt to treat tumor in deeper tissues by interacting long-wavelength light. LNVs were introduced to improve anticancer effect and photostability of P18 N AI ME. LNVs using glycerol monostearate demonstrated smaller particle sizes and more sustained release profiles than those using lauric acid. In photocytotoxicity against HeLa (human cervical carcinoma) and A549 (human lung carcinoma) cell lines, P18 N AI ME-LNVs demonstrated safety under dark conditions and enhanced anticancer effects under light conditions compared to P18 N AI ME alone. The inhibitory concentration values (IC₅₀) were 0.86 μM (P18 N AI ME) and 0.68 μM (LNVs) in HeLa cell line and 0.85 μM (P18 N AI ME) and 0.64 μM (LNVs) in A549 cell line. These findings suggest that P18 N AI ME-LNVs hold promise as PDT agents in cancer therapy.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006794","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":"Formulation development and feasibility of AAV5 as a lyophilized drug product.","authors":"Stephanie K Vargas, Farrokh Sharifi, Reinard Nambayan, Saeed Moshashaee, Teruna J Siahaan","doi":"10.1016/j.xphs.2025.01.004","DOIUrl":"10.1016/j.xphs.2025.01.004","url":null,"abstract":"<p><p>The majority of adeno-associated virus (AAV) gene therapies are currently developed as frozen formulations (e.g., ≤ - 60 °C) that are challenging to maintain and distribute world-wide. Lyophilization can allow for long-term refrigerated storage and improved shelf-life that lowers long-term cost. Here, we performed a lyophilization feasibility study to assess the ability of several different excipients to stabilize AAV5 during lyophilization and on storage stability. A range of biophysical techniques were used to assess capsid integrity on a molecular level including quantification of externalized DNA, capsid particle size, and capsid monomer percent area. Additionally, transmission electron microscopy was used for the first time to monitor the size and integrity of the capsids subjected to the lyophilization process, and the results supported other characterization methods used in this study. A formulation containing hydroxyectoine and trehalose stabilized capsid structure directly after lyophilization, as observed directly by 5.0 % of internally stained capsids (empty) and indirectly with 7.5 % external DNA. A recombinant human albumin and trehalose formulation stabilized capsid structure on stability as observed by improved external DNA and monomer profiles overtime. Adversely, mannitol crystallization negatively affected capsid structure. Our findings indicate that lyophilization is a viable option to frozen formulation for stabilizing AAV5 drug products.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007132","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":"Novel hybrid system based on carboxymethyl chitosan hydrogel encapsulating drug loaded nanoparticles for prolonged release of Vancomycin in the treatment of bacterial infection.","authors":"Lixia Pan, Dandan Wang, Haozhi Sun, Jie Song, Xin Shen, Feng Su, Suming Li","doi":"10.1016/j.xphs.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.01.012","url":null,"abstract":"<p><p>Current bacterial infections clinical treatments, such as intravenous antibiotic administration and local injection, suffer from short action duration, repeated administrations, and severe cell toxicity. To address these limitations, it is imperative to develop sustained drug release system with prolonged antimicrobial effects. In this work, a hybrid system was prepared using EDC/NHS catalyzed crosslinking-based carboxymethyl chitosan (CMCS) hydrogel as a carrier to encapsulate biodegradable nanoparticles (NPs) loaded with vancomycin, an efficient antibacterial drug. First, ring opening polymerization of L-lactide or L-lactide/glycolide mixture was performed in the presence of poly(ethylene glycol) (PEG) to yield PEG-PLA or PEG-PLGA block copolymers. Vancomycin was loaded in PEG-PLA or PEG-PLGA NPs using double emulsion method. Drug-loaded NPs were then encapsulated in the CMCS hydrogel. Drug release from NPs, CMCS hydrogel and hybrid NPs-hydrogel systems was performed, and release kinetics were analyzed using Korsmeyer-Peppas model. The established hybrid system exhibited prolonged drug release without burst release. Finally, the biocompatibility of the hybrid system was evidenced by the MTT, hemolysis, dynamic clotting time, and zebrafish embryotoxicity tests. Last but not least, the hybrid system displayed outstanding long-lasting antimicrobial activity as shown by co-culture with Monoclonal S. aureus, thus suggesting great potential for applications in bacterial infection treatment.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007140","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 voltammetric method for determining N-nitrosodimethylamine in losartan and olmesartan drugs.","authors":"Tassio A Nunes, Fernanda S Soares, João V M Mariz, Luciano B Ramo, Rossana O Nóbrega, Anabel S Lourenço, Amanda C Silva, Mario C U Araujo","doi":"10.1016/j.xphs.2025.01.002","DOIUrl":"10.1016/j.xphs.2025.01.002","url":null,"abstract":"<p><p>Recently, the National Health Surveillance Agency (ANVISA) of Brazil recalled several lots of sartan drugs due to the presence of N-nitrosodimethylamine (NDMA). NDMA is a highly potent carcinogenic contaminant that harms human health; therefore, the presence of NDMA in sartan drugs must be checked through appropriate analytical methods. This work successfully developed a new analytical method for determining NDMA without chemical pretreatment of losartan and olmesartan drug samples. The method uses the square-wave anodic stripping voltammetric (SWASV) technique, a boron-doped diamond electrode (BDDE), and a standard additions procedure (SAP). The proposed SWASV-BDDE-SAP method provided a linear response in the concentration range between 250 and 2500 nmol L^-1 (R² = 0.995, n = 10), a limit of detection (LOD) of 67.6 nmol L^-1, satisfactory accuracy (94.3% - 104.7%) without bias, and with good reproducibility (standard deviation = 5.6 %). The results obtained in determining NDMA in losartan and olmesartan drugs using the proposed and reference methods (HPLC-DAD) did not show a statistically significant difference, applying the paired t-test at a confidence level of 95%. In addition, the proposed method uses instrumentation with low acquisition, operation, and maintenance costs and enables rapid determination of NDMA in sartan drugs with great sensitivity, reproducibility, and stability. As the proposed SWASV-BDDE-SAP method does not use chemical pretreatment of samples, such as derivatization and/or extraction with reagents and/or organic solvents, it can be considered a promising eco-friendly alternative for determining NDMA in routine analysis, thus contributing to green analytical chemistry.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007280","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":"Comparative Analysis of Empty and Full Adeno-Associated Viruses under Stressed Conditions by Anion-Exchange Chromatography, Analytical Ultracentrifugation, and Mass Photometry.","authors":"Julia A Townsend, Shuai Li, Laura Sweezy, Nina Liu, Michael P Rosconi, Erica A Pyles, Li Zhi, Dingjiang Liu, Zhijie Wu, Haibo Qiu, Mohammed Shameem, Ning Li","doi":"10.1016/j.xphs.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.01.005","url":null,"abstract":"<p><p>Adeno-associated viruses (AAVs) have emerged as a promising gene delivery vehicle for the treatment of diseases. As AAVs are a complex therapeutic modality, new analytical techniques are needed to thoroughly characterize the critical quality attributes (CQAs) to support drug development. Empty and full ratio is one of the CQAs of AAVs that may impact drug safety and efficacy. While the empty and full ratio of AAV therapeutics in untreated conditions can be well characterized by different analytical methods, limited studies have demonstrated whether these analytical methods can be used for characterizing stressed AAVs, which can help with assessing the stability of the molecule and identify potential degradation pathways. Here, we employ three orthogonal analytical techniques - (1) anion-exchange chromatography (AEX), (2) analytical ultracentrifugation (AUC), and (3) recently introduced mass photometry (MP)-to investigate their ability to characterize AAV samples subjected to various stress conditions, including freeze/thaw, physical agitation, and thermal stress. Based on our observations, AEX is a high-throughput technique. However, it falls short in quantifying the amount of partially filled AAVs, and the quantification is significantly impacted by post-translational modifications, which often occur to AAVs under stress conditions. AUC provides the best resolution for stressed AAV samples but is limited by its throughput and high sample consumption. MP combines the strength of being high-throughput and requires the least amount of samples, albeit at the expense of lower resolution compared to AUC. Our study suggests that each of these three techniques, AEX, AUC and the emerging MP method, is suitable for characterizing empty and full AAV particles at various stages including under stress conditions throughout the lifecycle of drug development.</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":"143006646","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":"Safety, tolerability, pharmacokinetic, and pharmacodynamic of CZ1S injection for unilateral brachial plexus blockade in healthy Chinese adults: Double-blind, randomized, positive-controlled Phase I study.","authors":"Pengfei Zhao, Dongjie Feng, Haiying Wang, Ting Luo, Dandan Yang, Zourong Ruan, Linqiang Zhu, Min Yan, Bo Jiang","doi":"10.1016/j.xphs.2025.01.008","DOIUrl":"10.1016/j.xphs.2025.01.008","url":null,"abstract":"<p><p>CZ1S injection is a novel, extended-release local anaesthetic formulation of ropivacaine, classified as a type 2.2 new drug, with potential for post-operative analgesia by subcutaneous infiltration and peripheral nerve blockade. This study aimed to validate the superior properties of CZ1S over ropivacaine hydrochloride injection and to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of a single dose of brachial plexus block with CZ1S in healthy Chinese adults. The tolerability and PK profile of CZ1S were investigated following a unilateral brachial plexus injection in 24 healthy adults. Safety assessments were performed throughout the study and the PD effects of CZ1S injection for unilateral brachial plexus block were also evaluated. The results showed that CZ1S was slowly absorbed after a single injection in healthy subjects, with PK parameters of ropivacaine (including C_max, AUC_t and AUC_∞) increasing with the CZ1S doses. CZ1S demonstrated a prolonged and non-constant release profile compared to a single 75 mg injection of ropivacaine hydrochloride, resulting in a smooth and sustained blood concentration. CZ1S significantly prolonged the duration of sensory and motor blockade, and further analysis revealed a correlation between PK and sensory nerve block. The PK profile of CZ1S was enhanced compared to that of ropivacaine injection, and it was deemed safe and well tolerated in healthy Chinese adults, suggesting its potential application in postoperative analgesia. CLINICAL TRIAL REGISTRATION: Chinadrugtrials.org.cn: CTR20231295 (registration date: 26 April 2023).</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":"143007099","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":"The role of histidine buffer in the iron-catalyzed formation of oxidizing species in pharmaceutical formulations: Mechanistic studies.","authors":"Yilue Zhang, Yaqi Wu, Christian Schöneich","doi":"10.1016/j.xphs.2025.01.003","DOIUrl":"10.1016/j.xphs.2025.01.003","url":null,"abstract":"<p><p>Iron-catalyzed oxidation reactions are common degradation pathways in pharmaceutical formulations. Buffers can influence oxidation reactions promoted by iron (Fe) and hydrogen peroxide (H₂O₂). However, mechanistically, the specific role of buffers in such reactions is not well understood. Here, we investigate the formation of radical intermediates using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a probe. Interestingly, over the time course of our experiments histidine (His) is the only buffer that promotes significant radical production during Fe(III)-catalyzed decomposition of H₂O₂, in contrast to other common pharmaceutical buffers such as citrate, succinate, adipate, and 2-(N-morpholino)ethanesulfonic acid (MES). The critical role of His in these degradation reactions is attributed to its unique, higher affinity for Fe(II) as compared to Fe(III), facilitating the reduction of Fe(III) to Fe(II) and subsequent Fenton and/or Fenton-like reactions with H₂O₂.</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":"143007104","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":"FORMULATION DEVELOPMENT OF HIGHLY STABLE COLLAGENASE-CONTAINING HYDROGELS FOR WOUND HEALING.","authors":"Syeda Yamna Zia, Sofia Ahmed, Hafiza Sumaiyya Jamal, Mehvish Perveen, Muhammad Ali Sheraz, Zubair Anwar, Syed Abid Ali","doi":"10.1016/j.xphs.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.xphs.2025.01.009","url":null,"abstract":"<p><p>Collagenases are enzymes that break down collagen and are used in wound healing and treating various disorders. Currently, collagenase is commercially available in only ointment and injectable forms and is sensitive to various environmental factors. In the present study, different hydrogel formulations of collagenase have been prepared at pH 6.5 using carboxymethylcellulose sodium and zinc acetate with and without humectants such as propylene glycol (PG) and glycerin (GL) in varying concentrations. The formulated gels were stored at room temperature (25±2°C, 60±5% RH) and refrigerator temperature (5±3°C) for six months to evaluate their physical and up to six years for chemical stability. The gels were subjected to various tests, including organoleptic studies, spreadability, moisture content, swelling index, swelling/de-swelling, syneresis, viscosity, gelation time, and weight variation. The purity and molecular weight of collagenase have been determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). At the same time, its activity during the storage period was evaluated by gelatin zymography. Casein zymography was also performed to detect any caseinase contamination in the formulations. The release of the enzyme from different gel formulations was assessed using the Franz diffusion apparatus and analyzed by gelatin zymography. The results showed some physical changes that were more prominent in gels stored at room temperature than those kept refrigerated. The difference in humectant concentration was also found to affect the stability of gels. PG was found to be a better humectant than GL, particularly in a concentration of 25%. The zymography results indicated that collagenase was stable in all formulations kept in the refrigerator. In contrast, its complete degradation was noted in the preparations stored at room temperature within a month. The data generated in this study will help the formulators to commercialize a relatively economical gel formulation of collagenase that is highly stable for up to six years at refrigerator temperature (5±3°C).</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":"143007134","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":"Clotrimazole Mucoadhesive Films with Extended-Release Properties for Vaginal Candidiasis-A Hot-Melt Extrusion Application.","authors":"Kirti Sawant, Rasha M Elkanayati, Ahmed Almotairy, Michael Repka, Mashan Almutairi","doi":"10.1016/j.xphs.2025.01.011","DOIUrl":"https://doi.org/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":"Mechanism of low molecular weight impurity formation in an IgG1 monoclonal antibody formulation.","authors":"Pinaki Basu, Nidhi Verma, Sigireddi Indra Kumar, Maya Nanath, Sireesha Goswamy Kaligatla, Giridhar Sivalanka, Veerabhadra Madurai Veeraraghavan, Lovisha Aggarwal, Sunil A Nankar, Ravi Kumar Marikanti, Murali Jayaraman","doi":"10.1016/j.xphs.2024.12.024","DOIUrl":"10.1016/j.xphs.2024.12.024","url":null,"abstract":"<p><p>Formulation robustness study was performed for a biosimilar monoclonal antibody (IgG1) manufactured at Dr. Reddy's Laboratory, where the pH and concentration level of excipients in the drug product formulation were systematically varied from the target formulation. It was observed that the IgG1 formulation having relatively low pH and high citrate (buffer salt) concentration were predisposed to the formation of low molecular weight impurities. Mass spectrometry analysis of the mAb1 fragments detected the pyroglutamate species from LC-LC dimer and fragmentation in the -DKTH- amino acid sequence of the heavy chain. Blind docking indicated binding of citrate with Lysine 222 residue in the proximity of Cys224 could have potentially fragmented IgG1.</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":"143007139","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}