{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T19:43:41Z","timestamp":1773776621190,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFD1800904"],"award-info":[{"award-number":["2023YFD1800904"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFD1800900"],"award-info":[{"award-number":["2023YFD1800900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>Albendazole (ABZ), classified as a class II basic drug under the Biopharmaceutics Classification System (BCS), is widely recognized for its therapeutic efficacy in treating and preventing trichuriasis. However, despite its clinical relevance, ABZ\u2019s oral administration presents challenges due to its poor solubility and pH sensitivity, which diminish its therapeutic effectiveness. Additionally, high dosing regimens of ABZ pose risks of developmental toxicity in animal models. This study developed a pH-sensitive solid dispersion of albendazole (ABZ-pHs-SD) using Glyceryl Monostearate (GM) in conjunction with Hypromellose Acetate Succinate (HPMC-AS). Characterization via Scanning Electron Microscopy (SEM), Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FT-IR) confirmed the high dispersion of ABZ in a crystalline state within the carrier. Furthermore, we compared the <jats:italic>in vitro<\/jats:italic> dissolution profile, pharmacokinetics, and intestinal drug concentration of ABZ-pHs-SD with commercially available formulations. Our findings demonstrated that ABZ-pHs-SD exhibited an excellent dissolution profile, significantly increasing the solubility of ABZ in water by 3.15 times. The formulation effectively prevented drug release in acidic environments while maintaining a slow release in weakly alkaline conditions. Additionally, compared to commercial formulations, ABZ-pHs-SD showed significantly lower C<jats:sub>max<\/jats:sub> (4.70\u202f\u00b1\u202f1.16 vs. 6.83\u202f\u00b1\u202f0.66\u202f\u03bcg\/mL) and higher T<jats:sub>max<\/jats:sub> (5.5\u202f\u00b1\u202f0.93 vs. 3.75\u202f\u00b1\u202f0.71\u202fh) <jats:italic>in vivo<\/jats:italic>, achieving elevated drug concentration levels in the cecal and colonic environments (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.01) without significantly decreasing bioavailability. Overall, our research findings indicate that ABZ-pHs-SD serves as a promising drug delivery strategy for the poorly soluble and pH-sensitive ABZ. Particularly, the simple preparation of solid dispersion demonstrates strong industrial feasibility.<\/jats:p>","DOI":"10.3389\/fvets.2024.1522856","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T06:29:33Z","timestamp":1734676173000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Combining solubilization and controlled release strategies to prepare pH-sensitive solid dispersion loaded with albendazole: in vitro and in vivo studies"],"prefix":"10.3389","volume":"11","author":[{"given":"Dehai","family":"Su","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoqun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangyang","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuezhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangguang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanzhong","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1016\/S0140-6736(06)68653-4","article-title":"Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm","volume":"367","author":"Bethony","year":"2006","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/1756-3305-5-81","article-title":"The global limits and population at risk of soil-transmitted helminth infections in 2010","volume":"5","author":"Pullan","year":"2012","journal-title":"Parasit Vectors"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"637570","DOI":"10.3389\/fcimb.2021.637570","article-title":"Whipworm-associated intestinal microbiome members consistent across both human and mouse hosts","volume":"11","author":"Rosa","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41572-020-0171-3","article-title":"Whipworm and roundworm infections","volume":"6","author":"Else","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1146\/annurev-immunol-090222-101331","article-title":"Systemic immune modulation by gastrointestinal nematodes","volume":"42","author":"Kasal","year":"2024","journal-title":"Annu Rev Immunol"},{"key":"ref6","volume-title":"WHO model list of essential medicines for children (2nd list, march 2010 update)","year":"2010"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.ejpb.2004.03.001","article-title":"Classification of orally administered drugs on the World Health Organization model list of essential medicines according to the biopharmaceutics classification system","volume":"58","author":"Lindenberg","year":"2004","journal-title":"Eur J Pharm Biopharm"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/s0001-706x(96)00640-7","article-title":"Albendazole in treatment of human cystic echinococcosis: 12 years of experience","volume":"64","author":"Horton","year":"1997","journal-title":"Acta Trop"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/s00228-002-0488-8","article-title":"Effect of gender in the disposition of albendazole metabolites in humans","volume":"58","author":"Mirfazaelian","year":"2002","journal-title":"Eur J Clin Pharmacol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.2165\/00003088-198815020-00001","article-title":"Clinical pharmacokinetics of anthelmintic drugs","volume":"15","author":"Edwards","year":"1988","journal-title":"Clin Pharmacokinet"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/0035-9203(94)90525-8","article-title":"Albendazole and infections with Ascaris lumbricoides and Trichuris trichiura in children in Bangladesh","volume":"88","author":"Hall","year":"1994","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e25003","DOI":"10.1371\/journal.pone.0025003","article-title":"Efficacy of single-dose and triple-dose albendazole and mebendazole against soil-transmitted helminths and Taenia spp.: a randomized controlled trial","volume":"6","author":"Steinmann","year":"2011","journal-title":"PLoS One"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2535","DOI":"10.1128\/AAC.01317-13","article-title":"Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection","volume":"58","author":"Adegnika","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"ref14","first-page":"555","article-title":"Salt screening and characterization for poorly soluble, weak basic compounds: case study albendazole","volume":"68","author":"Paulekuhn","year":"2013","journal-title":"Pharmazie"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1016\/j.xphs.2019.03.007","article-title":"In vitro assessment of Supersaturation\/precipitation and biological membrane permeation of poorly water-soluble drugs: a case study with Albendazole and ketoconazole","volume":"108","author":"Kataoka","year":"2019","journal-title":"J Pharm Sci"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1016\/j.xphs.2016.06.016","article-title":"Studying the propensity of compounds to supersaturate: a practical and broadly applicable approach","volume":"105","author":"Palmelund","year":"2016","journal-title":"J Pharm Sci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"106","DOI":"10.18433\/j37606","article-title":"Prediction of oral absorption of low-solubility drugs by using rat simulated gastrointestinal fluids: the importance of regional differences in membrane permeability and solubility","volume":"17","author":"Tanaka","year":"2014","journal-title":"J Pharm Pharm Sci"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1006\/taap.1997.8114","article-title":"Disposition of netobimin, albendazole, and its metabolites in the pregnant rat: developmental toxicity","volume":"144","author":"Crist\u00f2fol","year":"1997","journal-title":"Toxicol Appl Pharmacol"},{"key":"ref19","first-page":"14","volume-title":"Albendazole: in evaluation of certain veterinary drug residues in food","year":"1989"},{"key":"ref20","first-page":"618","article-title":"Inhibition of albendazole crystallization in poly(vinylpyrrolidone) solid molecular dispersions","volume":"61","author":"Kalaiselvan","year":"2006","journal-title":"Pharmazie"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"220","DOI":"10.3390\/pharmaceutics13020220","article-title":"Relevance of liquid-liquid phase separation of supersaturated solution in Oral absorption of Albendazole from amorphous solid dispersions","volume":"13","author":"Suzuki","year":"2021","journal-title":"Pharmaceutics"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.1021\/acs.chemrev.0c00812","article-title":"Using microemulsions: formulation based on knowledge of their Mesostructure","volume":"121","author":"Gradzielski","year":"2021","journal-title":"Chem Rev"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1016\/j.xphs.2021.11.010","article-title":"Dissolution\/permeation of Albendazole in the presence of Cyclodextrin and bile salts: a mechanistic in vitro study into factors governing Oral bioavailability","volume":"111","author":"Eriksen","year":"2022","journal-title":"J Pharm Sci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3137","DOI":"10.1007\/s11095-015-1677-3","article-title":"Dual drug delivery using lactic acid conjugated SLN for effective Management of Neurocysticercosis","volume":"32","author":"Devi","year":"2015","journal-title":"Pharm Res"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.3390\/molecules22112040","article-title":"Solid lipid nanoparticles of Albendazole for enhancing cellular uptake and cytotoxicity against U-87 MG glioma cell lines","volume":"22","author":"Marslin","year":"2017","journal-title":"Molecules"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"106751","DOI":"10.1016\/j.ejps.2024.106751","article-title":"Enabling a novel solvent method on Albendazole solid dispersion to improve the in vivo bioavailability","volume":"196","author":"Han","year":"2024","journal-title":"Eur J Pharm Sci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.ijbiomac.2020.11.172","article-title":"Mung bean (Vigna radiata) porous starch for solubility and dissolution enhancement of poorly soluble drug by solid dispersion","volume":"167","author":"Nadaf","year":"2021","journal-title":"Int J Biol Macromol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.ijpharm.2016.01.006","article-title":"A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties","volume":"499","author":"Martinez-Marcos","year":"2016","journal-title":"Int J Pharm"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"7295","DOI":"10.3390\/molecules28217295","article-title":"The use of Cyclodextrin inclusion complexes to increase the solubility and pharmacokinetic profile of Albendazole","volume":"28","author":"Ding","year":"2023","journal-title":"Molecules"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.ejpb.2013.09.007","article-title":"Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs","volume":"85","author":"Vo","year":"2013","journal-title":"Eur J Pharm Biopharm"},{"key":"ref31","first-page":"1091","article-title":"Drug delivery: oral colon-specific","volume-title":"Encyclopedia of pharmaceutical science and technology","author":"Patel","year":"2013"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"241","DOI":"10.3109\/10611869408996806","article-title":"Targeting drugs to the colon: delivery systems for oral administration","volume":"2","author":"Ashford","year":"1994","journal-title":"J Drug Target"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1093\/jac\/dkp199","article-title":"High efficacy of albendazole-PEG 6000 in the treatment of Toxocara canis larva migrans infection","volume":"64","author":"Leonardi","year":"2009","journal-title":"J Antimicrob Chemother"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3731","DOI":"10.1002\/jps.22072","article-title":"Enantiotropically related albendazole polymorphs","volume":"99","author":"Pranzo","year":"2010","journal-title":"J Pharm Sci"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"623","DOI":"10.4155\/tde-2018-0037","article-title":"Development and in vitro evaluation of solid dispersions as strategy to improve albendazole biopharmaceutical behavior","volume":"9","author":"Simonazzi","year":"2018","journal-title":"Ther Deliv"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e0223320","DOI":"10.1128\/AAC.02233-20","article-title":"Improvement of the bioavailability and anti-hepatic alveolar echinococcosis effect of Albendazole-isethionate\/Hypromellose acetate succinate (HPMC-AS) complex","volume":"65","author":"Hu","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"4978","DOI":"10.1021\/acs.molpharmaceut.9b00851","article-title":"Enhanced Oral bioavailability and anti-echinococcosis efficacy of Albendazole achieved by optimizing the \"spring\" and \"parachute\"","volume":"16","author":"Hu","year":"2019","journal-title":"Mol Pharm"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejps.2005.02.017","article-title":"The use of an in vitro dissolution and absorption system to evaluate oral absorption of two weak bases in pH-independent controlled-release formulations","volume":"26","author":"Sugawara","year":"2005","journal-title":"Eur J Pharm Sci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s12917-023-03631-2","article-title":"Florfenicol sustained-release granules: an in vitro-in vivo correlation study in pigs","volume":"19","author":"Yang","year":"2023","journal-title":"BMC Vet Res"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.ijpharm.2017.10.051","article-title":"Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery \u2013 an update","volume":"535","author":"Jermain","year":"2018","journal-title":"Int J Pharm"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.jddst.2019.01.017","article-title":"Characterization of amorphous solid dispersions: an update","volume":"50","author":"Ma","year":"2019","journal-title":"J Drug Deliv Sci Technol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.powtec.2015.04.044","article-title":"Preparation and characterization of solid dispersion using a novel amphiphilic copolymer to enhance dissolution and oral bioavailability of sorafenib","volume":"2015","author":"Truong","year":"2015","journal-title":"Powder Technol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1208\/s12249-020-01802-0","article-title":"Characterizing and exploring the differences in dissolution and stability between crystalline solid dispersion and amorphous solid dispersion","volume":"21","author":"Wang","year":"2020","journal-title":"AAPS PharmSciTech"},{"key":"ref44","first-page":"353","volume-title":"Contrasting the gastrointestinal tracts of mammals: factors that influence absorption","author":"DeSesso","year":"2008"},{"key":"ref45","volume-title":"Guidance for industry: Dissolution testing of immediate release solid Oral dosage forms","year":"1997"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"134","DOI":"10.3390\/pharmaceutics11030134","article-title":"Formulation development of Albendazole-loaded self-microemulsifying chewable tablets to enhance dissolution and bioavailability","volume":"11","author":"Sawatdee","year":"2019","journal-title":"Pharmaceutics"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"433","DOI":"10.3109\/00498259509061863","article-title":"Small intestinal sulphoxidation of albendazole","volume":"25","author":"Villaverde","year":"1995","journal-title":"Xenobiotica"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1046\/j.1365-2125.2000.00170.x","article-title":"Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes","volume":"49","author":"Rawden","year":"2000","journal-title":"Br J Clin Pharmacol"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/s0140-6736(83)92533-3","article-title":"Albendazole as a potential treatment for human hydatidosis","volume":"322","author":"Saimot","year":"1983","journal-title":"Lancet"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/s0001-706x(03)00031-7","article-title":"Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics","volume":"86","author":"Dayan","year":"2003","journal-title":"Acta Trop"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/BF03189665","article-title":"Transplacental transport of netobimin metabolites in ewes","volume":"20","author":"Cristofol","year":"1995","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"ref52","first-page":"131","article-title":"Placental and fetal toxicity of albendazole sulphoxide in Wistar rats","volume":"45","author":"Teruel","year":"2003","journal-title":"Vet Hum Toxicol"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/j.1365-2885.1984.tb00890.x","article-title":"A correlation of toxicity of albendazole and oxfendazole with their free metabolites and bound residues","volume":"7","author":"Delatour","year":"1984","journal-title":"J Vet Pharmacol Ther"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"434","DOI":"10.3109\/10837450.2012.693509","article-title":"Enhanced dissolution and systemic availability of albendazole formulated as solid dispersions","volume":"18","author":"Castro","year":"2013","journal-title":"Pharm Dev Technol"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2024.1522856\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T11:43:42Z","timestamp":1737114222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2024.1522856\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,20]]},"references-count":54,"alternative-id":["10.3389\/fvets.2024.1522856"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2024.1522856","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,20]]},"article-number":"1522856"}}