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https://hdl.handle.net/10356/141828
Title: | Proof-of-concept preparation and characterization of dual-drug amorphous nanoparticle complex as fixed-dose combination of poorly soluble drugs | Authors: | Yu, Hong Lim, Li Ming Dong, Bingxue Hadinoto, Kunn |
Keywords: | Engineering::Chemical engineering | Issue Date: | 2019 | Source: | Yu, 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/10.1080/03639045.2018.1522327 | Journal: | Drug Development and Industrial Pharmacy | Abstract: | Objectives: 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. | URI: | https://hdl.handle.net/10356/141828 | ISSN: | 0363-9045 | DOI: | 10.1080/03639045.2018.1522327 | Schools: | School of Chemical and Biomedical Engineering | Rights: | This 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. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SCBE Journal Articles |
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Proof of Concept Preparation and Characterization of Dual Drug Amorphous Nanoparticle Complex as Fixed Dose Combination of Poorly Soluble Drugs.pdf | 628.39 kB | Adobe PDF | View/Open |
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