{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:58:22Z","timestamp":1785412702843,"version":"3.56.0"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22508422"],"award-info":[{"award-number":["22508422"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273880"],"award-info":[{"award-number":["82273880"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22478439"],"award-info":[{"award-number":["22478439"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["22508422"],"award-info":[{"award-number":["22508422"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82273880"],"award-info":[{"award-number":["82273880"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["22478439"],"award-info":[{"award-number":["22478439"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Jiangsu Province Frontier Technology Research Program","award":["BF2024075"],"award-info":[{"award-number":["BF2024075"]}]},{"name":"Lingang Laboratory","award":["LGL-2613-03"],"award-info":[{"award-number":["LGL-2613-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Long-acting injectable aqueous suspensions based on fatty acid prodrugs offer a compelling strategy for chronic disease management. However, the selection of optimal alkyl chain length remains largely empirical, as its influence on prodrug performance is highly system-dependent and lacks predictive guidelines. Methods: Three aripiprazole prodrugs with different alkyl chain lengths were synthesized and characterized using 1H-NMR spectroscopy and single-crystal X-ray diffraction. A series of physicochemical assessments was performed, including melting point, solubility, lipophilicity, solid-state stability, and plasma stability. The prodrugs were subsequently formulated as aqueous suspensions, which were evaluated for particle size, morphology, release behavior, cytotoxicity, and cellular uptake. Finally, intramuscular administration in rats was carried out to investigate pharmacokinetic profiles and local tolerability. Results: Physicochemical characterization revealed that chain elongation progressively reduced the melting point, solubility, wettability, and solid-state stability of these prodrugs, whereas their flexibility, lipophilicity, and plasma stability correspondingly increased. After wet milling and intramuscular administration in rats, all suspensions sustained drug release for up to one month with good tolerability. Notably, the aripiprazole lauroxil formulation exhibited superior bioavailability and a shortened subtherapeutic interval, enabling the rapid attainment of therapeutic concentrations while effectively mitigating a prolonged pharmacokinetic tail. Conclusions: These findings reinforce the favorable profile of aripiprazole lauroxil as a lead candidate and demonstrate that isostructural packing facilitates the reliable prediction of chain length\u2013property correlations across diverse fatty acid-prodrug systems, thus providing a valuable reference for rational alkyl chain selection in the design of fatty acid-based LAI suspensions.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080911","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Alkyl Chain Length on Physicochemical and Pharmacokinetic Performance of Aripiprazole Fatty Acid Prodrugs for Long-Acting Injectable Suspensions"],"prefix":"10.3390","volume":"18","author":[{"given":"An","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7510-9295","authenticated-orcid":false,"given":"Ting","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, China"},{"name":"Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114862","DOI":"10.1016\/j.addr.2023.114862","article-title":"Long-acting parenteral drug delivery systems for the treatment of chronic diseases","volume":"198","author":"Jindal","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114721","DOI":"10.1016\/j.jconrel.2026.114721","article-title":"Insights into development of long-acting injectable suspensions","volume":"392","author":"Malavia","year":"2026","journal-title":"J. Control. Release"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S2215-0366(21)00039-0","article-title":"Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: A systematic review and comparative meta-analysis of randomised, cohort, and pre\u2013post studies","volume":"8","author":"Kishimoto","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1021\/acs.molpharmaceut.4c00665","article-title":"Patient-centric long-acting injectable and implantable platforms\u2014An industrial perspective","volume":"21","author":"Alidori","year":"2024","journal-title":"Mol. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41578-021-00405-w","article-title":"Clinical translation of long-acting drug delivery formulations","volume":"7","author":"Li","year":"2022","journal-title":"Nat. Rev. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114898","DOI":"10.1016\/j.jconrel.2026.114898","article-title":"A cocrystal-based long-acting injectable suspension platform enables tunable drug release","volume":"394","author":"Chen","year":"2026","journal-title":"J. Control. Release"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/j.apsb.2025.12.003","article-title":"Crystal engineering for poorly water-soluble drugs: From design to applications","volume":"16","author":"Chen","year":"2026","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114901","DOI":"10.1016\/j.addr.2023.114901","article-title":"Recent advances in lipid-based long-acting injectable depot formulations","volume":"199","author":"Sharma","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114860","DOI":"10.1016\/j.addr.2023.114860","article-title":"Prodrug approaches for the development of a long-acting drug delivery systems","volume":"198","author":"Chien","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1007\/s40265-017-0848-4","article-title":"Aripiprazole lauroxil: A review in schizophrenia","volume":"77","author":"Frampton","year":"2017","journal-title":"Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.2165\/11208640-000000000-00000","article-title":"Extended-release intramuscular paliperidone palmitate a review of its use in the treatment of schizophrenia","volume":"72","author":"Carter","year":"2012","journal-title":"Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/mp500070m","article-title":"Making the leap from daily oral dosing to long-acting injectables: Lessons from the antipsychotics","volume":"11","author":"Remenar","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_13","unstructured":"Fran, M.K.J., Embrechts, R.C.A., Borghijs, H.K., and Monbaliu, J. (2000). Aqueous Suspensions of 9-Hydroxyrisperidone Fatty Acid Esters. (U.S. Patent US6077843)."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ejpb.2023.06.013","article-title":"Creation of a ready-to-use brexpiprazole suspension and the inflammation-mediated pharmacokinetics by intramuscular administration","volume":"189","author":"Wang","year":"2023","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jconrel.2019.09.001","article-title":"Creation of a long-acting rilpivirine prodrug nanoformulation","volume":"311\u2013312","author":"Hilaire","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6825","DOI":"10.1039\/D6TB00997B","article-title":"Crystallization of lipidated dexamethasone prodrugs: The linker matters","volume":"14","author":"Dong","year":"2026","journal-title":"J. Mater. Chem. B"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.schres.2014.09.021","article-title":"Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia","volume":"159","author":"Turncliff","year":"2014","journal-title":"Schizophr. Res."},{"key":"ref_18","first-page":"16764","article-title":"A randomized, double-blind, placebo-controlled trial of aripiprazole lauroxil in acute exacerbation of schizophrenia","volume":"76","author":"Srdjan","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.rinphs.2014.04.002","article-title":"Biological conversion of aripiprazole lauroxil\u2014An n-acyloxymethyl aripiprazole prodrug","volume":"4","author":"Rohde","year":"2014","journal-title":"Results Pharma Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1586\/17512433.2016.1121809","article-title":"Aripiprazole long-acting injectable formulations for schizophrenia: Aripiprazole monohydrate and aripiprazole lauroxil","volume":"9","author":"Citrome","year":"2016","journal-title":"Expert. Rev. Clin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): A comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_22","unstructured":"Pomares Marco, M., Marquillas Olondriz, F.D.A., Bessa Bellmunt, J., and De Le\u00f3n Mart\u00edn, A.A. (2019). Process for the Preparation of Aripiprazole Lauroxil. (U.S. Patent WO2019020821)."},{"key":"ref_23","unstructured":"Perry, J.M., Hickey, M.B., Remenar, J.F., and Vandiver, J. (2013). Pharmaceutical Compositions Comprising Benzyl Alcohol. (U.S. Patent WO2013142205)."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"122434","DOI":"10.1016\/j.molliq.2023.122434","article-title":"Thermodynamic analysis and molecular dynamic simulation of solid\u2013liquid equilibrium behavior of antipsychotic drug aripiprazole (form iii) in three binary solvent mixtures","volume":"385","author":"Wang","year":"2023","journal-title":"J. Mol. Liq."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1002\/jps.21574","article-title":"Conformational polymorphism in aripiprazole: Preparation, stability and structure of five modifications","volume":"98","author":"Braun","year":"2009","journal-title":"J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1039\/B203191B","article-title":"Fingerprinting intermolecular interactions in molecular crystals","volume":"4","author":"Spackman","year":"2002","journal-title":"CrystEngComm"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1039\/B818330A","article-title":"Hirshfeld surface analysis","volume":"11","author":"Spackman","year":"2009","journal-title":"CrystEngComm"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.1021\/acs.cgd.0c00427","article-title":"Interaction map driven cocrystallization of ambrisentan: Structural and biopharmaceutical evaluation","volume":"20","author":"Haneef","year":"2020","journal-title":"Cryst. Growth Des."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1021\/acs.cgd.5c01675","article-title":"Harnessing supramolecular self-assembly of ethionamide and sorbic acid through cocrystallization: A promising alternative for tuberculosis treatment","volume":"26","author":"Ayala","year":"2026","journal-title":"Cryst. Growth Des."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.addr.2020.11.008","article-title":"Clinically established biodegradable long acting injectables: An industry perspective","volume":"167","author":"Nkanga","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1007\/s00775-010-0676-4","article-title":"Antiproliferative pt (iv) complexes: Synthesis, biological activity, and quantitative structure\u2013activity relationship modeling","volume":"15","author":"Gramatica","year":"2010","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0021-9673(00)91610-8","article-title":"Relationship between log pow, shake-flask values and capacity factors derived from reversed-phase high-performance liquid chromatography for n-alkylbenzenes and some oecd reference substances","volume":"282","author":"Harnisch","year":"1983","journal-title":"J. Chromatogr. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ejpb.2014.12.014","article-title":"Lipophilic prodrugs of apomorphine I: Preparation, characterisation, and in vitro enzymatic hydrolysis in biorelevant media","volume":"89","author":"Borkar","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"122298","DOI":"10.1016\/j.ijpharm.2022.122298","article-title":"Stabilizer-induced different in vivo behaviors for intramuscularly long-acting celecoxib nanocrystals","volume":"628","author":"Qin","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/s41563-020-0674-z","article-title":"A year-long extended release nanoformulated cabotegravir prodrug","volume":"19","author":"Kulkarni","year":"2020","journal-title":"Nat. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1038\/s41467-026-68501-5","article-title":"An ultra-long-acting dimeric bictegravir prodrug defined by a short pharmacokinetic tail","volume":"17","author":"Nayan","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2205429","DOI":"10.1002\/smll.202205429","article-title":"Quantitative evaluation of the cellular uptake of nanodiamonds by monocytes and macrophages","volume":"19","author":"Niora","year":"2023","journal-title":"Small"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2419263","DOI":"10.1002\/adma.202419263","article-title":"The optimized lipid-modified prodrug for CNV treatment","volume":"37","author":"Lv","year":"2025","journal-title":"Adv. Mater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"18532","DOI":"10.1021\/jacs.2c07833","article-title":"Medium-chain lipid conjugation facilitates cell-permeability and bioactivity","volume":"144","author":"Morstein","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_40","unstructured":"(2026, June 21). Center for Drug Evaluation and Research, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2015\/207533Orig1s000PharmR.pdf."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.drudis.2017.01.003","article-title":"The in vivo fate of nanocrystals","volume":"22","author":"Lu","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/17425247.2019.1588248","article-title":"Development and evaluation of intramuscularly administered nano\/microcrystal suspension","volume":"16","author":"Ma","year":"2019","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jconrel.2016.03.041","article-title":"The effect of macrophage and angiogenesis inhibition on the drug release and absorption from an intramuscular sustained-release paliperidone palmitate suspension","volume":"230","author":"Darville","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1002\/jps.24014","article-title":"Intramuscular administration of paliperidone palmitate extended-release injectable microsuspension induces a subclinical inflammatory reaction modulating the pharmacokinetics in rats","volume":"103","author":"Darville","year":"2014","journal-title":"J. Pharm. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.jconrel.2021.12.011","article-title":"Effect of particle size on in vivo performances of long-acting injectable drug suspension","volume":"341","author":"Ho","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s13346-017-0428-x","article-title":"Regulating the alky chain length of fatty acid-didanosine prodrugs and evaluating its role in albumin binding","volume":"8","author":"Chen","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1038\/s41467-022-30902-7","article-title":"Transformation of dolutegravir into an ultra-long-acting parenteral prodrug formulation","volume":"13","author":"Deodhar","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ijpharm.2018.03.042","article-title":"Microsuspension of fatty acid esters of entecavir for parenteral sustained delivery","volume":"543","author":"Ho","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1002\/jps.10239","article-title":"Straight-chain naltrexone ester prodrugs: Diffusion and concurrent esterase biotransformation in human skin","volume":"91","author":"Stinchcomb","year":"2002","journal-title":"J. Pharm. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.jconrel.2016.04.029","article-title":"Lipophilic nalmefene prodrugs to achieve a one-month sustained release","volume":"232","author":"Gaekens","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"16270","DOI":"10.1039\/c3ra41967c","article-title":"Novel n-5-(acyloxyalkoxy)carbonyl prodrugs of olanzapine with physicochemical properties for extended-release","volume":"3","author":"Blumberg","year":"2013","journal-title":"RSC Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/jps.2600790616","article-title":"Ester prodrugs of zidovudine","volume":"79","author":"Kawaguchi","year":"1990","journal-title":"J. Pharm. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1246\/bcsj.20150405","article-title":"Drug release is determined by the chain length of fatty acid-conjugated anticancer agent as one component of nano-prodrug","volume":"89","author":"Koseki","year":"2016","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1107\/S2052252523009582","article-title":"The role of alkyl chain length in the melt and solution crystallization of paliperidone aliphatic prodrugs","volume":"11","author":"Chen","year":"2024","journal-title":"IUCrJ"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1017\/S0885715616000087","article-title":"Crystal structure of paliperidone, C23H27FN4O3","volume":"31","author":"Kaduk","year":"2016","journal-title":"Powder Diffr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1107\/S160053681104164X","article-title":"Paliperidone: 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]eth-yl}-9-hy-droxy-2-methyl-1,6,7,8,9,9a-hexa-hydro-pyrido[1,2-a]pyrimidin-4-one","volume":"67","author":"Betz","year":"2011","journal-title":"Acta Crystallogr. Sect. E Struct. Rep. Online"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1021\/cg400358e","article-title":"Evaluating the roles of conformational strain and cohesive binding in crystalline polymorphs of aripiprazole","volume":"13","author":"Delaney","year":"2013","journal-title":"Cryst. Growth Des."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/nrd1494","article-title":"Nanosuspensions in drug delivery","volume":"3","author":"Rabinow","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Jacob, S., Kather, F.S., Boddu, S.H.S., Attimarad, M., and Nair, A.B. (2025). Nanosuspension innovations: Expanding horizons in drug delivery techniques. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17010136"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ejps.2012.10.004","article-title":"Identifying the correlation between drug\/stabilizer properties and critical quality attributes (CQAs) of nanosuspension formulation prepared by wet media milling technology","volume":"48","author":"George","year":"2013","journal-title":"Eur. J. Pharm. Sci."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/8\/911\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:41:51Z","timestamp":1784878911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/8\/911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["pharmaceutics18080911"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18080911","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}