Formulation optimization and evaluation of metformin hydrochloride orally disintegrating tablets using spray drying and D-optimal design of experiments

Formulation optimization and evaluation of metformin hydrochloride orally disintegrating tablets using spray drying and D-optimal design of experiments | 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 Formulation optimization and evaluation of metformin hydrochloride orally disintegrating tablets using spray drying and D-optimal design of experiments Mohamad Farhan Roslan, Kesvini Thiruvarselva, Mahibub Mahamadsa Kanakal, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7395029/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Feb, 2026 Read the published version in Journal of Pharmaceutical Innovation → Version 1 posted You are reading this latest preprint version Abstract Purpose Metformin hydrochloride (Met.HCl) current dosage form were found to be inconvenient for individuals with dysphagia. This situation underscores the need for orally disintegrating tablets (ODT) as an alternative dosage form. Method This research utilizes a co-spray drying method to formulate taste-masked Met.HCl optimal for ODT formulation. Formulation design and optimization were achieved using a D-optimal design of experiments (DOE) approach to obtain desired tablet properties, such as hardness and disintegration time. Results Spray drying enabled the homogenous distribution of excipients, lowered crystallinity, and improved the physicochemical characteristics of Met.HCl powder, overcoming the limitation of physical blending techniques. The optimized formulation of Met.HCl ODT exhibited outstanding tensile strength between 1.90 and 2.43 MPa, fast disintegration times of 18 to 24 seconds, and total drug release within 5 minutes. Conclusion These results demonstrate the potential of spray drying as a particle engineering technique to enhance the physicochemical and functional properties of Met.HCl powder. This improvement supports the formulation of Met.HCl ODT offers a viable alternative for T2DM patients, particularly those with dysphagia. Orally disintegrating tablets metformin hydrochloride spray drying co-processing dysphagia diabetes mellitus type 2 Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Feb, 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. 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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-7395029","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":507037114,"identity":"e352fc5b-e64a-485b-9471-fc00fd4f622d","order_by":0,"name":"Mohamad Farhan Roslan","email":"","orcid":"","institution":"University of Malaya","correspondingAuthor":false,"prefix":"","firstName":"Mohamad","middleName":"Farhan","lastName":"Roslan","suffix":""},{"id":507037115,"identity":"b2c6f4cd-ac86-42a4-a4ca-cd4e399317be","order_by":1,"name":"Kesvini Thiruvarselva","email":"","orcid":"","institution":"University of Malaya","correspondingAuthor":false,"prefix":"","firstName":"Kesvini","middleName":"","lastName":"Thiruvarselva","suffix":""},{"id":507037116,"identity":"04db8240-aca1-4214-8368-6e65e272cfab","order_by":2,"name":"Mahibub Mahamadsa Kanakal","email":"","orcid":"","institution":"Quest International University Perak","correspondingAuthor":false,"prefix":"","firstName":"Mahibub","middleName":"Mahamadsa","lastName":"Kanakal","suffix":""},{"id":507037117,"identity":"9f6252bb-206e-4ee2-baff-cf45538d2b99","order_by":3,"name":"Zamri Chik","email":"","orcid":"","institution":"University of Malaya","correspondingAuthor":false,"prefix":"","firstName":"Zamri","middleName":"","lastName":"Chik","suffix":""},{"id":507037118,"identity":"47921b65-eab0-44d4-9972-3286d31f9d34","order_by":4,"name":"Riyanto Teguh Widodo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwUlEQVRIiWNgGAWjYDACZgglByZ5iNeSwGBMghYGiJbEBqK1mLfzGH4u/GGTvuHaAcYHb9sYog0OENAic5jHWHpGQlruhtsJzIZz2xhyNxDSIsHMYyDNk3AYpIVNmpdILca/gVrSDW4nsP8mVosZyJYEoBY2ZiK1sJVZ86SlGc68ndgsOeecRO5Mglr4D2++zWNjI893O/nghzdlNrl9hLQwMHAYQBmMDSAjGBQIa2F/gMqXbyCoZRSMglEwCkYYAADjETyYDplSgAAAAABJRU5ErkJggg==","orcid":"","institution":"University of Malaya","correspondingAuthor":true,"prefix":"","firstName":"Riyanto","middleName":"Teguh","lastName":"Widodo","suffix":""}],"badges":[],"createdAt":"2025-08-18 02:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7395029/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7395029/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12247-026-10386-4","type":"published","date":"2026-02-18T15:58:37+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":103251620,"identity":"0b93b1e0-8de3-4d36-b2ee-3961e8fbc997","added_by":"auto","created_at":"2026-02-23 16:11:08","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1748981,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7395029/v1_covered_64fc247f-3c71-403b-bf1f-cba764be0f3d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Formulation optimization and evaluation of metformin hydrochloride orally disintegrating tablets using spray drying and D-optimal design of experiments","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":"Orally disintegrating tablets, metformin hydrochloride, spray drying, co-processing, dysphagia, diabetes mellitus type 2","lastPublishedDoi":"10.21203/rs.3.rs-7395029/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7395029/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eMetformin hydrochloride (Met.HCl) current dosage form were found to be inconvenient for individuals with dysphagia. This situation underscores the need for orally disintegrating tablets (ODT) as an alternative dosage form.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e\u003cp\u003eThis research utilizes a co-spray drying method to formulate taste-masked Met.HCl optimal for ODT formulation. Formulation design and optimization were achieved using a D-optimal design of experiments (DOE) approach to obtain desired tablet properties, such as hardness and disintegration time.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eSpray drying enabled the homogenous distribution of excipients, lowered crystallinity, and improved the physicochemical characteristics of Met.HCl powder, overcoming the limitation of physical blending techniques. The optimized formulation of Met.HCl ODT exhibited outstanding tensile strength between 1.90 and 2.43 MPa, fast disintegration times of 18 to 24 seconds, and total drug release within 5 minutes.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThese results demonstrate the potential of spray drying as a particle engineering technique to enhance the physicochemical and functional properties of Met.HCl powder. This improvement supports the formulation of Met.HCl ODT offers a viable alternative for T2DM patients, particularly those with dysphagia.\u003c/p\u003e","manuscriptTitle":"Formulation optimization and evaluation of metformin hydrochloride orally disintegrating tablets using spray drying and D-optimal design of experiments","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 15:22:41","doi":"10.21203/rs.3.rs-7395029/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":"c8ef11f3-8a82-410e-b3de-9accfe0dc77b","owner":[],"postedDate":"September 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T16:08:14+00:00","versionOfRecord":{"articleIdentity":"rs-7395029","link":"https://doi.org/10.1007/s12247-026-10386-4","journal":{"identity":"journal-of-pharmaceutical-innovation","isVorOnly":false,"title":"Journal of Pharmaceutical Innovation"},"publishedOn":"2026-02-18 15:58:37","publishedOnDateReadable":"February 18th, 2026"},"versionCreatedAt":"2025-09-01 15:22:41","video":"","vorDoi":"10.1007/s12247-026-10386-4","vorDoiUrl":"https://doi.org/10.1007/s12247-026-10386-4","workflowStages":[]},"version":"v1","identity":"rs-7395029","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7395029","identity":"rs-7395029","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}