Drug Development and Industrial Pharmacy最新文献

{"title":"Enhancement in the Antibacterial Activity of Rifaximin by Delivery through Gelatin Nanoparticles.","authors":"Nida Iqbal,Amber Bano,Daim Asif Raja,Ali Raza,Rabia Ilyas,Rafia Akhlaq,Imran Saleem,Ayaz Ahmed,Syed Ghulam Musharraf,Muhammad Imran Malik","doi":"10.1080/03639045.2024.2405622","DOIUrl":"https://doi.org/10.1080/03639045.2024.2405622","url":null,"abstract":"OBJECTIVESBacterial infections are a noteworthy global health concern that necessitates the development of new strategies to enhance the potency and efficacy of antibiotics. Rifaximin (RFX), a broad-spectrum antibiotic, exhibits promising antibacterial activity against several bacterial strains. However, its insolubility and impermeability impede the exploitation of its full potential. The objective of the current study is to overcome the inherent caveats of RFX in order to exploit its maximum potential.SIGNIFICANCEThe exploitation of the full potential of antibiotics is necessary for reduction in their dosage and to minimize antibiotic pollution. This is a preliminary study aiming for maximum utilization of RFX at the target site and reduction in its release in unmetabolized form.METHODSGelatin is a biopolymer that has gained significant attention for biomedical applications owing to its inherent biocompatibility and biodegradability. In this study, bovine gelatin nanoparticles (BGNPs) were fabricated by the self-assembly method for their application as a carrier of RFX to enhance its antibacterial activity. The study employs a comprehensive range of experimental techniques to characterize the fabricated BGNPs such as DLS, Zeta Potential, FT-IR, AFM, SEM-EDX, and UV-Vis spectrophotometry.RESULTSThe average size of the fabricated BGNPs was 100 nm with a zeta potential value of -15.3 mV. The loading of RFX on BGNPs rendered an increase in its size to 136 nm with a zeta potential value of -16 mV. In-vitro assays and microscopic analyses were conducted to compare the antibacterial efficacy of RFX and RFX@BGNPs. An excellent loading capacity followed by sustained release of RFX from RFX@BGNPs rendered a significant enhancement in its pharmaceutical efficacy. The release of RFX from RFX@BGNPs followed the Higuchi and Korsmeyer-Peppasmodels. The antibacterial efficacy of RFX against Staphylococcus aureus has doubled by delivery through RFX@BGNPs, assessed by inhibitory and biofilm inhibitory assays. The enhancement in the antibacterial efficiency was further endorsed by SEM and microscopic imaging of the control and treated bacterial colonies.CONCLUSIONThe study demonstrates an enhancement in the antimicrobial efficacy of RFX by its delivery in the form of RFX@BGNPs to exploit its full potential for practical applications.","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro anticancer efficacy of Calendula Officinalis extract-loaded chitosan nanoparticles against gastric and colon cancer cells.","authors":"Rabia Yilmaz Ozturk,Rabia Cakir","doi":"10.1080/03639045.2024.2404143","DOIUrl":"https://doi.org/10.1080/03639045.2024.2404143","url":null,"abstract":"OBJECTIVEThis study assessed the anticancer activities of calendula officinalis-loaded chitosan nanoparticles in gastric and colon cancer cells compared to fibroblast cells and examined the balance between ROS and antioxidants.METHODSConsidering this information, we synthesized Calendula officinalis-loaded chitosan nanoparticles (CO-CSNPs) via the ionic gelation method. Their characterizations were carried out with ZetaSizer, UV-Vis, FTIR and SEM devices including size, morphology and surface zeta potential analysis, loading capacity, encapsulation efficiency, in vitro drug release, and chemical interactions. The anticancer activities of CO, CSNPs, and CO-CSNPs were tested against AGS, Caco-2, and normal NIH-3T3 cells using an XTT assay. The anticancer effects were evaluated with the DAPI staining, scratch assay, reactive oxygen species (ROS) detection and CUPRAC method on cellular and non-cellular processes that promote anticancer mechanisms.RESULTSResults showed that CO and CO-CNPs exhibited anticancer activity against AGS and Caco-2. Further, the formulation of CO with CSNPs enhanced the anticancer activity of CO while having no cytotoxicity on NIH-3T3. DAPI staining, scratch assay, ROS, and CUPRAC method confirmed the anticancer activity of CO and CO-CSNPs, which resulted in a reduction in the number of apoptotic cells, inhibited migration, triggered apoptotic pathway via ROS, and higher antioxidant activity.CONCLUSIONSThe results of the study indicate that CO-CSNPs are a promising therapeutic formulation for gastric and colon cancer treatment. We consider that this study will lead to the investigation of molecular mechanisms of CO-CSNPs in cancer treatment and their investigation in clinical studies.","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poly(lactic acid hydroxyacetic acid)-poly(ethylene glycol)-modified ginsenoside Rg3 nanomedicine enhances anti-tumor effect in hepatocellular carcinoma.","authors":"Wei Zheng,Yuqiao Huang,Qiong Wu,Pu Cheng,Song Yujun,Ben Wang,Qi Huang,Shen Hu","doi":"10.1080/03639045.2024.2402769","DOIUrl":"https://doi.org/10.1080/03639045.2024.2402769","url":null,"abstract":"OBJECTIVEThis research aim to improve bioavailability and anti-hepatocellular carcinoma (HCC) efficacy of Ginsenoside Rg3 by modification with poly (lactic acid hydroxyacetic acid)-poly(ethylene glycol) (PLGA-PEG).METHODSPLGA-PEG-Rg3 was obtained by emulsification and evaluated it physiochemical characterization by FTIR, SEM, laser particle-size analyser and HPLC. The effect of the PLGA-PEG-Rg3 and Rg3 on HepG2 cells was compared in vitro studies, including cell proliferation, transwell and a series of apoptosis detection, and in-situ HCC model.RESULTSThe PLGA-PEG-Rg3 were 122 nm in size and 0.112 in polydispersity index with sustained release profile in vitro. Compared to Rg3, PLGA-PEG-Rg3 was more effective in suppressing HepG2 growth and inducing apoptosis by mitochondrial apoptosis pathway in vitro. and PLGA-PEG modification enhanced the liver-targeting ability and drug circulation time of Rg3 in vivo, resulting in PLGA-PEG-Rg3 possessed superior performance in inhibiting tumor growth and prolonging survival time of tumor-bearing mice than Rg3.CONCLUSIONSOverall, these results showed PLGA-PEG-Rg3 enhanced anti-tumor effect of Rg3 in HCC.","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparative anticancer analysis of iron oxide nanoparticles of <i>Hippophae rhamnoides</i> and <i>Cichorium intybus</i> found in the Karakoram Range of Gilgit Baltistan against liver cancer targeting the <i>RhoA</i> gene.","authors":"Rukhsana Tabassum, Erum Dilshad","doi":"10.1080/03639045.2024.2400209","DOIUrl":"10.1080/03639045.2024.2400209","url":null,"abstract":"<p><strong>Objective: </strong>The current research work focused on the evaluation of of <i>H. rhamnoides</i> and <i>C. intybus</i> Fe₂O₃ NPs against liver cancer cell line (HepG2) by performing antiproliferative assay targeting the <i>RhoA</i> gene and apoptotic pathway genes and proteins.</p><p><strong>Methods: </strong>Fe₂O₃ NPs were synthesized using extracts of <i>H. rhamnoides</i> and <i>C. intybus</i> and characterized by UV-Vis spectroscopy, FTIR, SEM/EDS and XRD. MTT assay was used to study cytotoxicity against the HepG2 cells. Real-time qPCR and ELISA were used for the gene and protein analysis.</p><p><strong>Results: </strong>An absorbance peak at 300 nm for <i>H. rhamnoides</i> and 289 nm for <i>C. intybus</i> nanoparticles were observed by UV-Vis analysis. The FTIR bands of <i>H. rhamnoide</i> Fe₂O₃ NPs suggested the presence of aldehydes, alcohols and polyols whereas bands of <i>C. intybus</i> Fe₂O₃ NPs suggested the presence of carboxyl groups, hydroxyl groups, alkynes and amines. The size of Fe₂O₃ NPs was found to be 27 ± 5nm for <i>H. rhamnoides</i> and 84 ± 4nm for <i>C. intybus.</i> The IC₅₀ value of 41.69 µM for <i>H. rhmnoides</i> and 71.04 µM for <i>C. intybus</i> Fe₂O₃ NPs compared to plant extract (78.10 and 96.03 µM for <i>H. rhamnoides</i> and <i>C. intybus</i>, respectively<i>)</i> were found against HepG2 cells. The gene expression and protein levels of <i>RhoA</i> were decreased whereas those of <i>bax</i>, <i>caspase 3</i>, <i>caspase 8</i> and <i>caspase 9</i> were found increased.</p><p><strong>Conclusion: </strong>Nanoparticles and extract of <i>H. rhamnoides</i> were found more effective as compared to <i>C. intybus</i>, which was evident by the results of cytotoxicity and analysis of studied genes and proteins.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality by design (QbD) based approach for development of itraconazole-loaded transferosomes for skin cancer: <i>in vitro, ex vivo</i> and cell line studies.","authors":"Priya Kudi, Srijita Sen, Satyajit Murkute, Purusottam Mohapatra, Om Prakash Ranjan","doi":"10.1080/03639045.2024.2400203","DOIUrl":"10.1080/03639045.2024.2400203","url":null,"abstract":"<p><strong>Objective: </strong>Itraconazole (ITZ), a widely used systemic antifungal drug, has been ingeniously repurposed for its antitumor effects. In the present work, we have prepared and optimized the ITZ-loaded transferosomes by Quality by Design (QbD) approach and repurposed them for skin cancer.</p><p><strong>Methods: </strong>The transferosomal formulation was optimized by employing a QbD approach with the design of experiment. A combination of screening and optimization design was used for formulation optimization. The optimized formulation was characterized by particle size, PDI, zeta potential, FTIR, XRD, and surface morphology using TEM. <i>In vitro</i> and <i>ex vivo</i> studies were performed using Franz diffusion cells. An <i>in vitro</i> cell line study was performed on the human melanoma A375 cell line.</p><p><strong>Results: </strong>The optimized formulation has a particle size of 192.37 ± 13.19 nm, PDI of 0.41 ± 0.03, zeta potential -47.80 ± 3.66, and an entrapment efficiency of 64.11 ± 3.75%. <i>In vitro</i> release studies showed that ITZ encapsulated transferosomes offer higher and sustained release than pure drugs. <i>Ex vivo</i> drug penetration and retention studies show that the penetration and retention of transferosomes are more visible in the skin than in the drug. The cell viability study confirms that ITZ encapsulated transferosomes have almost 2-fold more potency against the A375 cell line than pure drug.</p><p><strong>Conclusion: </strong>ITZ encapsulated transferosomes were successfully prepared and optimized using a combination of screening and optimization designs. Based on <i>ex vivo</i> and cell line studies, we conclude that ITZ-loaded transferosomes could aid melanoma management alongside standard therapies.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the cytotoxic potential of acamprosate and acamprosate loaded mesoporous silica nanoparticles in hepatocellular carcinoma: an <i>in vitro</i> and <i>in silico</i> approach.","authors":"Suhail Ahmad Bhat, Sathyapriya Chandramohan, Srividya Subramanian, Sankar Pajaniradje, Neena Yadav, Rukkumani Rajagopalan","doi":"10.1080/03639045.2024.2400202","DOIUrl":"10.1080/03639045.2024.2400202","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a healthcare concern that causes most cancer-linked deaths around the world. This work was aimed at unraveling the anticancer potential of acamprosate and development of mesoporous silica nanoparticle (MSN) drug delivery system to increase the therapeutic efficacy of acamprosate. For this purpose, the MSNs were synthesized and encapsulated with acamprosate (MSN-Acamp). The MSN and MSN-Acamp were characterized by DLS, Zeta potential, UV spectroscopy, SEM, FTIR, XRD, DFT, and XPS. Biological effects were evaluated by MTT and lactate dehydrogenase assays. The apoptotic mode of cell death was evaluated by fluorescence imaging and DNA fragmentation assay. Cell cycle assessment and Annexin V-FITC/PI staining were performed to depict the phase of cell arrest and stage of apoptotic cells respectively. The acamprosate was found to exhibit cytotoxic effect and MSN-Acamp exhibited an increased cytotoxicity. Apoptotic mode of cell death was revealed by fluorescence imaging as nuclear fragmentation, production of reactive oxygen species (ROS), loss of membrane potential in mitochondria, and chromatin condensation/fragmentation were found. The docking results revealed that acamprosate had a considerable binding affinity with Bcl-2, Mcl-1, EGFR, and mTOR proteins. Overall, our results indicated that acamprosate and MSN-Acamp had a potent apoptotic effect and MSNs are propitious drug carriers to increase therapeutic effect in HCC.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chrysin-functionalized gold nanoparticles and paclitaxel exhibit synergistic impact on lung cancer cell lines via regulating the AKT/PPAR-ϒ/β-catenin pathway.","authors":"Saheli Roy, Shashi Kant, Krishna Das Saha, Tarun Jha","doi":"10.1080/03639045.2024.2393327","DOIUrl":"10.1080/03639045.2024.2393327","url":null,"abstract":"<p><p>Lung cancer has become progressively widespread, posing a challenge to traditional chemotherapeutic drugs such as platinum compounds and paclitaxel (PTX) owing to growing resistance. Along with that, the chemotherapeutic drugs infer major side effects. The usage of natural compounds as chemosensitizers to boost the efficacy of these chemotherapeutic drugs and minimizing their toxicity is a plausible approach. In our investigation, we employed PTX as the standard chemotherapeutic agent and utilized chrysin-functionalized gold nanoparticles (CHR-AuNPs) to augment its cytotoxicity. Gold nanoparticles were chosen for their inherent cytotoxic properties and ability to enhance chrysin's bioavailability and solubility. Characterization of CHR-AuNP revealed spherical nanoparticles within the nano-size range (35-70 nm) with a stable negative zeta potential of -22 mV, confirmed by physicochemical analyses including UV-visible spectroscopy, Fourier transform infrared (FTIR) spectral analysis, and visual observation of the wine-red coloration. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay cytotoxicity studies demonstrated CHR-AuNP's superior efficacy compared to CHR alone, with synergistic effects observed in combination with PTX, validated by Compusyn software. Morphological changes indicative of apoptosis were more pronounced with combined treatment, corroborated by acridine orange/ethidium bromide (AO/EtBr) staining and Annexin V assays. Furthermore, the combination treatment amplified reactive oxygen species (ROS) production and destabilized mitochondrial membrane potential, while altering the expression of pro-apoptotic and anti-apoptotic proteins. Exploring the mechanistic pathways, we found that the drugs upregulated PPAR-γ expression while suppressing Akt and overexpressing PTEN, thereby impeding the Wnt/β-catenin pathway commonly dysregulated in lung cancer. This highlights the potential of low-dose combination therapy with PTX and CHR-AuNP as a promising strategy for addressing lung cancer's challenges.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and optimization of naringin-loaded MOF-5 encapsulated by liponiosomes as smart drug delivery, cytotoxicity, and apoptotic on breast cancer cells.","authors":"Lina M Alneghery, Mohammed Al-Zharani, Fahd A Nasr, Zienab E Eldin, Tayel A Al Hujran, Hesham M Tawfeek, Mohamed H Fayed, Shehab Elbeltagi","doi":"10.1080/03639045.2024.2388786","DOIUrl":"10.1080/03639045.2024.2388786","url":null,"abstract":"<p><strong>Introduction: </strong>Cancers are regarded as hazardous due to their high worldwide death rate, with breast cancer (BC), which affects practically all cancer patients globally, playing a significant role in this statistic. The therapeutic approach for BC has not advanced using standard techniques, such as specialized naringin (NG) chemotherapy. Instead, a novel strategy has been utilized to enhance smart drug delivery (SDD) to tumors.</p><p><strong>Significance: </strong>Herein, we established NG-loaded zinc metal-organic framework-5 (NG-MOF-5) coated with liponiosomes (LNs) to manufacture NG-MOF-5@LNs nanoparticles (NPs) for antibacterial and cancer treatment.</p><p><strong>Methods: </strong>MOF-5, NG, and NG-MOF-5@LNs were evaluated with XRD, thermogravimetric analysis (TGA), FTIR, SEM, TEM, PDI, ZP, encapsulation efficiency (EE), loading efficiency (LE), and drug release (DR) kinetics. We examined the antibacterial activity involving minimum inhibitory concentration (MIC) and zone of inhibition by NG, MOF-5, and NG-MOF-5@LNs. The cell viability, necrosis, and total apoptosis (late and early) were evaluated for anti-cancer activity against MCF-7 BC cells.</p><p><strong>Results: </strong>TEM results demonstrated that NG-MOF-5@LNs formed monodispersed spherical-like particles with a size of 122.5 nm, PDI of 0.139, and ZP of +21 mV. The anti-microbial activity results indicated that NG-MOF-5@LNs exhibited potent antibacterial effects, as evidenced by inhibition zones and MIC values. The Higuchi model indicates an excellent fit (<i>R</i>² = 0.9988). The MTT assay revealed anti-tumor activity against MCF-7 BC cells, with IC₅₀ of 21 µg/mL for NG-MOF-5@LNs and demonstrating a total apoptosis effect of 68.2% on MCF-7 cells.</p><p><strong>Conclusion: </strong>NG-MOF-5@LNs is anticipated to show as an effective antimicrobial and novel long-term-release antitumor agent and might be more suitable for MCF-7 cell therapy.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability-indicating green HPLC method for fixed-dose tablets containing remogliflozin etabonate and teneligliptin: an AQbD approach.","authors":"Raj Patel, Rajendra Kotadiya","doi":"10.1080/03639045.2024.2400199","DOIUrl":"10.1080/03639045.2024.2400199","url":null,"abstract":"<p><strong>Background: </strong>In June 2021, the Central Drug Standards Control Organization approved a fixed-dose combination tablet containing remogliflozin etabonate (100 mg) and teneligliptin (10 mg) to manage type II diabetes.</p><p><strong>Objective: </strong>This study aims to develop a stability-indicating RP-HPLC method for quantifying remogliflozin etabonate and teneligliptin in tablet formulations <i>via</i> analytical quality by design (AQbD) principles.</p><p><strong>Methods: </strong>Risk assessment, Plackett-Burman design, and central composite design were employed to understand the impact of independent variables on critical analytical attributes. The stationary phase was a HyperClone BDS C18 column, and the mobile phase consisted of acetonitrile and phosphate buffer (20 mM, pH 5) at a 45:55% (v/v) ratio.</p><p><strong>Results: </strong>The method, validated per ICH Q2 (R1), resulted in retention times of 3.395 and 12.308 min for teneligliptin and remogliflozin etabonate, respectively. Forced degradation studies confirmed robustness, with clear peak separation and no interference from degradation products. The AGREE score of 0.65 supports its green applicability for tablet analysis in quality control.</p><p><strong>Conclusion: </strong>The AQbD-assisted RP-HPLC method developed in this study offers environmental friendliness, efficient separation with well-defined peaks, and simple mobile phase combination.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocrystal formulations of mebendazole employing quality by design and molecular level insights by atomistic simulations.","authors":"Elisavet Vardaka, Kyriakos Kachrimanis","doi":"10.1080/03639045.2024.2398597","DOIUrl":"10.1080/03639045.2024.2398597","url":null,"abstract":"<p><strong>Objective: </strong>The present study investigates the production of mebendazole nanocrystal formulations by wet media milling.</p><p><strong>Significance: </strong>Nanocrystal formulations are expected to enhance the dissolution properties of mebendazole, which possesses poor solubility, highly dependent on crystal polymorphism.</p><p><strong>Methods: </strong>A Box-Behnken design was employed to study the effects of formulation and process variables on the nanocrystal size and ζ-potential. The optimal nanosuspensions were solidified by spay-drying and freeze-drying with and without mannitol, and the effects of the drying method on the reconstitution of the nanosuspension was studied. Additionally, their physicochemical properties were determined, while the mechanism of fracture and stabilizer adsorption were investigated by atomistic simulations.</p><p><strong>Results: </strong>Poloxamer 407 is the most suitable stabilizer, while the bead size, milling speed, and stabilizer content significantly affect the diameter. The ζ-potential is affected by the stabilizer concentration depending on bead size. Energy-vector diagrams revealed a slip plane in the lattice of form C, while molecular dynamics simulations revealed strong interactions between stabilizer and crystal surface. Both drying processes induce polymorphic transformation to form A, which, however, can be partially prevented by the addition of mannitol in freeze-drying, at the expense of suspension redispersibility. The spray-dried nanosuspensions exhibited substantially enhanced dissolution profile compared to neat mebendazole, probably due to reduction of particle size, despite transformation to the unfavorable form A.</p><p><strong>Conclusions: </strong>Nanocrystal formulations exhibited significant dissolution enhancement, while experimental design and atomistic simulations provided useful insights into the mechanism of their formation and stability.</p>","PeriodicalId":11263,"journal":{"name":"Drug Development and Industrial Pharmacy","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}