Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/141828
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dc.contributor.authorYu, Hongen_US
dc.contributor.authorLim, Li Mingen_US
dc.contributor.authorDong, Bingxueen_US
dc.contributor.authorHadinoto, Kunnen_US
dc.date.accessioned2020-06-11T03:14:44Z-
dc.date.available2020-06-11T03:14:44Z-
dc.date.issued2019-
dc.identifier.citationYu, H., Lim, L. M., Dong, B. & Hadinoto, K. (2019). Proof-of-concept preparation and characterization of dual-drug amorphous nanoparticle complex as fixed-dose combination of poorly soluble drugs. Drug Development and Industrial Pharmacy, 45(1), 105-116. https://dx.doi.org/10.1080/03639045.2018.1522327en_US
dc.identifier.issn0363-9045en_US
dc.identifier.urihttps://hdl.handle.net/10356/141828-
dc.description.abstractObjectives: To carry out a proof-of-concept study on the development of dual-drug amorphous nanoparticle complex (nanoplex in short) as a potential formulation platform for fixed-dose combination (FDC) of poorly-soluble drugs. Significance: FDC has been proven effective in improving patient compliance for treatment that requires complex multidrug regimen. Currently, there is growing interest to develop FDC of poorly-soluble drugs due to the increased number of drugs exhibiting poor solubility thus low bioavailability. Methods: The dual-drug nanoplex was prepared by electrostatically-driven co-complexation of drug molecules with oppositely charged dextran sulfate, using ciprofloxacin (CIP) and itraconazole (ITZ) as the model poorly-soluble drugs. Results: We first verified that the co-complexation products were dual-drug CIP-ITZ nanoplex, and not binary mixtures of the single-drug CIP and ITZ nanoplexes, by demonstrating their distinct thermal behaviors and dissolution characteristics. Depending on the preparation condition, the dual-drug nanoplex exhibited size and zeta potential of 160–410 nm and −35–50 mV, respectively. The individual drug payloads were readily manipulated by varying the CIP/ITZ mass ratio in the feed, resulting in CIP and ITZ payloads in the range of 60-30% and 15-45%, respectively. The CIP-ITZ nanoplex, however, exhibited diminished CIP supersaturation generation, thus lower CIP solubility enhancement, compared to the single-drug CIP nanoplex. The CIP-ITZ nanoplex, nonetheless, remained capable of generating high ITZ supersaturation level. Conclusion: Dual-drug nanoplex was successfully prepared with a high degree of control over its physical characteristics. Nevertheless, whether dual-drug nanoplex always exhibits diminished solubility enhancement compared to its single-drug counterparts needs to be investigated using different poorly-soluble drugs.en_US
dc.language.isoenen_US
dc.relation.ispartofDrug Development and Industrial Pharmacyen_US
dc.rightsThis is an Accepted Manuscript of an article published by Informa UK Limited, trading as Taylor and Francis in Drug Development and Industrial Pharmacy on 25 Sep 2018, available online: http://www.tandfonline.com/10.1080/03639045.2018.1522327.en_US
dc.subjectEngineering::Chemical engineeringen_US
dc.titleProof-of-concept preparation and characterization of dual-drug amorphous nanoparticle complex as fixed-dose combination of poorly soluble drugsen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Chemical and Biomedical Engineeringen_US
dc.identifier.doi10.1080/03639045.2018.1522327-
dc.description.versionAccepted versionen_US
dc.identifier.pmid30196726-
dc.identifier.scopus2-s2.0-85053872778-
dc.identifier.issue1en_US
dc.identifier.volume45en_US
dc.identifier.spage105en_US
dc.identifier.epage116en_US
dc.subject.keywordsNanoparticlesen_US
dc.subject.keywordsAmorphizationen_US
dc.description.acknowledgementThe authors would like to acknowledge the funding from GlaxoSmithKline (GSK) Singapore under their Green and Sustainable Manufacturing Trust Fund 2013 (PI: Kunn Hadinoto Ong).en_US
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