Implementing Quality by Design (Qbd) Strategy for Optimization of lyophilized Solid Lipid Nanoparticles to Boost Oral Bioavailability of antimalarial drug

Implementing Quality by Design (Qbd) Strategy for Optimization of lyophilized Solid Lipid Nanoparticles to Boost Oral Bioavailability of antimalarial drug | 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 Implementing Quality by Design (Qbd) Strategy for Optimization of lyophilized Solid Lipid Nanoparticles to Boost Oral Bioavailability of antimalarial drug Neha Bajwa, Preet Amol Singh, Jitender Madan, Ashish Baldi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4303388/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Arteether (ART) is artemisinin derivatives drug used for resistant malaria. It has oral bioavailability of almost 0.98 %. AIM: ART loaded solid lipid nanoparticles (SLN) were developed with enhanced bioavailability using Quality by Design approach. Methodology: ART loaded SLNs were prepared by solvent emulsification/evaporation method using Quality by Design approach. Surfactant concentration and acetone to ethanol volume ratio were selected as independent variable while particle size and entrapment efficiency was selected as responses using central composite design. Result: The produced SLN were lyophilized and the powdered SLNs was encapsulated in an enteric coated capsule shell. The particle diameters of all the formulations were between 109 and 250 nm, and the entrapment effectiveness was 93.7 %. The XRD spectrum revealed that the ART was in amorphous form. The ART-SLNs release pattern revealed that ART was released in a slow yet time-dependent manner, which seems beneficial to prevent it from acid degradation. The permeability of ART containing formulations was investigated using the Franz diffusion cell technique. The concentration of ART employing ART-SLN to pure ART in the pig's intestine was nearly 7.1 fold enhanced. The pharmacokinetics of ART-SLN administered orally to rabbit models was investigated. The bioavailability of ART-loaded SLN was increased to 27.64%. Conclusion: These findings suggest that formulation development by using quality-by-design in present study also provide a comprehensive solution to develop oral formulation of arteether with desired bioavailability at industrial scale. Arteether Acid degradation Bioavailability Freeze drying Permeability Solid Lipid Nanoparticles Solubility Full Text Supplementary Files graphicalabstract222.png highlights1.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Reject after review 27 Aug, 2024 Reviewers agreed at journal 23 Jul, 2024 Reviewers invited by journal 25 Apr, 2024 Editor assigned by journal 25 Apr, 2024 First submitted to journal 23 Apr, 2024 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-4303388","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":295552443,"identity":"ff4b5cc1-0d76-4e22-9185-471d9cccb8c6","order_by":0,"name":"Neha Bajwa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYFACHgZmBgY2Bgb2/o+Pf1QABZiZG4jUwnPA2JjhDEgLI1FagEAiwUyYsQ3EIqDFnL334OeCGr7E/oaENObCebXR/O1ALT8qtuHUYtlzLll6xjG2xBkHDhx7PHPb8dwZhxkbGHvO3MapxeBGjoE0DxtbbsPBxnYD3m3HchuAWpgZ2/Bouf/G+DfPP7bc+YeZ2SR45xwDMghpucFjJs3bxpa74RgbmzRvQ03uBoJazuSYWc/sY6vfeIaH2XDGsQO5G4FaDuL1y/EzxrcLvh0zlrv/hvHBh5q63HnnDx988KMCtxYoOAZjHAaTBwipB4IaGKOOCMWjYBSMglEw0gAAIsRgS4ywDhAAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-5940-761X","institution":"Baba Farid University of Health Sciences","correspondingAuthor":true,"prefix":"","firstName":"Neha","middleName":"","lastName":"Bajwa","suffix":""},{"id":295552444,"identity":"71e18e20-54bc-4501-ad16-3c0ff043681b","order_by":1,"name":"Preet Amol Singh","email":"","orcid":"","institution":"Baba Farid University of Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Preet","middleName":"Amol","lastName":"Singh","suffix":""},{"id":295552445,"identity":"fcb0f875-34c7-48de-ab5f-47ef75690bef","order_by":2,"name":"Jitender Madan","email":"","orcid":"","institution":"National Institute of Pharmaceutical Education and Research Hyderabad","correspondingAuthor":false,"prefix":"","firstName":"Jitender","middleName":"","lastName":"Madan","suffix":""},{"id":295552446,"identity":"9afc84b2-cf04-4b28-b943-488f37a08252","order_by":3,"name":"Ashish Baldi","email":"","orcid":"","institution":"Maharaja Ranjit Singh State Technical University: Maharaja Ranjit Singh Punjab Technical University","correspondingAuthor":false,"prefix":"","firstName":"Ashish","middleName":"","lastName":"Baldi","suffix":""}],"badges":[],"createdAt":"2024-04-22 05:53:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4303388/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4303388/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55703058,"identity":"6e8c8fcd-738e-44d4-b2f6-8e9b06df1c0c","added_by":"auto","created_at":"2024-05-02 04:03:23","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1002304,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4303388/v1_covered_34237b4c-3048-4d38-a7da-b983e1ba5916.pdf"},{"id":55702481,"identity":"feba4618-8550-4c3a-91d8-56a306510465","added_by":"auto","created_at":"2024-05-02 03:55:20","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":1725090,"visible":true,"origin":"","legend":"","description":"","filename":"graphicalabstract222.png","url":"https://assets-eu.researchsquare.com/files/rs-4303388/v1/132c165c342711acb970cb0d.png"},{"id":55702294,"identity":"24ce98f8-319a-4108-a0d1-f517361475e4","added_by":"auto","created_at":"2024-05-02 03:47:20","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":16501,"visible":true,"origin":"","legend":"","description":"","filename":"highlights1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4303388/v1/ccd22d5908156003a7c3b562.docx"}],"financialInterests":"","formattedTitle":"Implementing Quality by Design (Qbd) Strategy for Optimization of lyophilized Solid Lipid Nanoparticles to Boost Oral Bioavailability of antimalarial drug","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"acta-parasitologica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"actp","sideBox":"Learn more about [Acta Parasitologica](http://link.springer.com/journal/11686)","snPcode":"11686","submissionUrl":"https://submission.springernature.com/new-submission/11686/3","title":"Acta Parasitologica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Arteether, Acid degradation, Bioavailability, Freeze drying, Permeability, Solid Lipid Nanoparticles, Solubility","lastPublishedDoi":"10.21203/rs.3.rs-4303388/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4303388/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eArteether (ART) is artemisinin derivatives drug used for resistant malaria. \u0026nbsp;It has oral bioavailability of almost 0.98 %.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAIM:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eART loaded solid lipid nanoparticles (SLN) were developed with enhanced bioavailability using Quality by Design approach.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eART loaded SLNs were prepared by solvent emulsification/evaporation method using Quality by Design approach. Surfactant concentration and acetone to ethanol volume ratio were selected as independent variable while particle size and entrapment efficiency was selected as responses using central composite design.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe produced SLN were lyophilized and the powdered SLNs was encapsulated in an enteric coated capsule shell. The particle diameters of all the formulations were between 109 and 250 nm, and the entrapment effectiveness was 93.7 %. The XRD spectrum revealed that the ART was in amorphous form. The ART-SLNs release pattern revealed that ART was released in a slow yet time-dependent manner, which seems beneficial to prevent it from acid degradation.\u003c/p\u003e\n\u003cp\u003eThe permeability of ART containing formulations was investigated using the Franz diffusion cell technique. The concentration of ART employing ART-SLN to pure ART in the pig's intestine was nearly 7.1 fold enhanced.\u003c/p\u003e\n\u003cp\u003eThe pharmacokinetics of ART-SLN administered orally to rabbit models was investigated. \u0026nbsp;The bioavailability of ART-loaded SLN was increased to 27.64%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThese findings suggest that formulation development by using \u0026nbsp;quality-by-design in present study also provide a comprehensive solution to develop oral formulation of arteether with desired bioavailability at industrial scale.\u003c/p\u003e","manuscriptTitle":"Implementing Quality by Design (Qbd) Strategy for Optimization of lyophilized Solid Lipid Nanoparticles to Boost Oral Bioavailability of antimalarial drug","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-02 03:47:15","doi":"10.21203/rs.3.rs-4303388/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Reject after review","date":"2024-08-27T04:38:54+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-07-24T03:52:16+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-25T18:53:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-25T04:43:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"Acta Parasitologica","date":"2024-04-23T06:32:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"acta-parasitologica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"actp","sideBox":"Learn more about [Acta Parasitologica](http://link.springer.com/journal/11686)","snPcode":"11686","submissionUrl":"https://submission.springernature.com/new-submission/11686/3","title":"Acta Parasitologica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"05d5d77a-d3de-40eb-9577-cf180528e961","owner":[],"postedDate":"May 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-05-02T03:47:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-02 03:47:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4303388","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4303388","identity":"rs-4303388","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}