QbD-Guided Formulation and Optimization of Lyophilized Dry Emulsion of Nicardipine Hydrochloride Employing Caprylic Capric, Tween 80, and Transcutol® HP Using Box–Behnken Design

QbD-Guided Formulation and Optimization of Lyophilized Dry Emulsion of Nicardipine Hydrochloride Employing Caprylic Capric, Tween 80, and Transcutol® HP Using Box–Behnken Design | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article QbD-Guided Formulation and Optimization of Lyophilized Dry Emulsion of Nicardipine Hydrochloride Employing Caprylic Capric, Tween 80, and Transcutol® HP Using Box–Behnken Design Rahul Yuvraj Pagar, Avinash Balasaheb Gangurde This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8248811/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Apr, 2026 Read the published version in Journal of Pharmaceutical Innovation → Version 1 posted You are reading this latest preprint version Abstract Purpose The study developed and optimized a lyophilized dry emulsion (LDE) of nicardipine hydrochloride (NHCl) using a pseudo-ternary phase diagram (PTPD) and a Box–Behnken design (BBD) to enhance aqueous solubility and to obtain a free-flowing, compressible powder suited for solid dosage form development. Methods A PTPD was constructed using caprylic capric (CC), Smix (Tween 80 and Transcutol® HP, 1:1), and a water phase (WP) containing maltodextrin and sodium alginate to define the emulsifying region. A BBD with CC, Smix, WP, temperature, and vacuum as independent variables was used to generate formulations. The solubility responses of these formulations were analyzed by Analysis of Variance (ANOVA) and response surface methodology (RSM) to identify an optimized batch. The optimized LDE (OLDE) was prepared under the predicted conditions and evaluated for zeta potential, solubility, flow properties, X-ray diffraction (XRD), and Scanning Electron Microscope (SEM). Results The PTPD identified an emulsification region, and BBD analysis revealed Smix, CC, and WP as key factors influencing solubility. The OLDE exhibited a solubility of 1.698 ± 0.010 mg/mL, higher than the pure NHCl. It showed good flow properties-Angle of repose 29.85°, Hausner ratio (HR) 1.15, Carr’s index (CI) 13.09% and a zeta potential of − 26.2 mV, indicating emulsion stability. XRD and SEM analyses confirmed reduced crystallinity and formation of amorphous matrix. Conclusion A PTPD-guided and BBD-OLDE successfully enhanced the aqueous solubility and flow properties of NHCl. The OLDE of NHCl exhibited good physicochemical and solid-state characteristics, supporting promising platform for the NHCl solid oral dosage forms. Nicardipine Lyophilization Dry Emulsion Solubility QbD Box-Behnken Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Apr, 2026 Read the published version in Journal of Pharmaceutical Innovation → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8248811","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":560231487,"identity":"6d7d125b-022f-4803-98a8-c863c6422817","order_by":0,"name":"Rahul Yuvraj Pagar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYHACNgaGAjCD8QGQ4OEjTosBmMEMonjYSNHCJgHl4gfm7YefPeYxuCMv7372WeXXHDsZNgbmh49u4NEicybN3JjH4JnhxjPpZrdltyUDHcZmbJyDR4sEQ4KZNI/BYcaNDWlstyW3MQO18LBJ49XC//wbSIv9xv5nbMWS2+qJ0CKRA7Ylcb5EGhvjx22HidHypkxyjsGz5A0Sz5ilGbcd52FjJuQX/vRtEm8q7tjO709j/PhzW7U9P3vzw8f4tEDBAQaDA8C45AGxmQkrh2iRbwCmmB/EqR4Fo2AUjIIRBgAq7UG0C+VHnAAAAABJRU5ErkJggg==","orcid":"","institution":"K.B.H.S.S. 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Optimization of Lyophilized Dry Emulsion of Nicardipine Hydrochloride Employing Caprylic Capric, Tween 80, and Transcutol® HP Using Box–Behnken Design\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Nicardipine, Lyophilization, Dry Emulsion, Solubility, QbD, Box-Behnken","lastPublishedDoi":"10.21203/rs.3.rs-8248811/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8248811/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe study developed and optimized a lyophilized dry emulsion (LDE) of nicardipine hydrochloride (NHCl) using a pseudo-ternary phase diagram (PTPD) and a Box\u0026ndash;Behnken design (BBD) to enhance aqueous solubility and to obtain a free-flowing, compressible powder suited for solid dosage form development.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA PTPD was constructed using caprylic capric (CC), Smix (Tween 80 and Transcutol\u0026reg; HP, 1:1), and a water phase (WP) containing maltodextrin and sodium alginate to define the emulsifying region. A BBD with CC, Smix, WP, temperature, and vacuum as independent variables was used to generate formulations. The solubility responses of these formulations were analyzed by Analysis of Variance (ANOVA) and response surface methodology (RSM) to identify an optimized batch. The optimized LDE (OLDE) was prepared under the predicted conditions and evaluated for zeta potential, solubility, flow properties, X-ray diffraction (XRD), and Scanning Electron Microscope (SEM).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe PTPD identified an emulsification region, and BBD analysis revealed Smix, CC, and WP as key factors influencing solubility. The OLDE exhibited a solubility of 1.698\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010 mg/mL, higher than the pure NHCl. It showed good flow properties-Angle of repose 29.85\u0026deg;, Hausner ratio (HR) 1.15, Carr\u0026rsquo;s index (CI) 13.09% and a zeta potential of \u0026minus;\u0026thinsp;26.2 mV, indicating emulsion stability. XRD and SEM analyses confirmed reduced crystallinity and formation of amorphous matrix.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eA PTPD-guided and BBD-OLDE successfully enhanced the aqueous solubility and flow properties of NHCl. The OLDE of NHCl exhibited good physicochemical and solid-state characteristics, supporting promising platform for the NHCl solid oral dosage forms.\u003c/p\u003e","manuscriptTitle":"QbD-Guided Formulation and Optimization of Lyophilized Dry Emulsion of Nicardipine Hydrochloride Employing Caprylic Capric, Tween 80, and Transcutol® HP Using Box–Behnken Design","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-17 12:46:38","doi":"10.21203/rs.3.rs-8248811/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b67fa862-6057-47de-9742-3cc4f92526a2","owner":[],"postedDate":"December 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-20T16:14:54+00:00","versionOfRecord":{"articleIdentity":"rs-8248811","link":"https://doi.org/10.1007/s12247-026-10682-z","journal":{"identity":"journal-of-pharmaceutical-innovation","isVorOnly":false,"title":"Journal of Pharmaceutical Innovation"},"publishedOn":"2026-04-18 15:59:13","publishedOnDateReadable":"April 18th, 2026"},"versionCreatedAt":"2025-12-17 12:46:38","video":"","vorDoi":"10.1007/s12247-026-10682-z","vorDoiUrl":"https://doi.org/10.1007/s12247-026-10682-z","workflowStages":[]},"version":"v1","identity":"rs-8248811","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8248811","identity":"rs-8248811","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}