Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine

Objective: The objective of this study is to develop a new solubility enhancement strategy of anti- psychotic drug – perphenazine (PPZ) – in the form of its amorphous nanoparticle complex (or nanoplex) with polyelectrolyte dextran sulfate (DXT). Significance: Poor bioavailability of PPZ necessitated...

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Main Authors: Dong, Bingxue, Hadinoto, Kunn
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/141825
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1418252020-06-22T02:04:15Z Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine Dong, Bingxue Hadinoto, Kunn School of Chemical and Biomedical Engineering Pharmacy Engineering::Chemical engineering Amorphization Supersaturation Objective: The objective of this study is to develop a new solubility enhancement strategy of anti- psychotic drug – perphenazine (PPZ) – in the form of its amorphous nanoparticle complex (or nanoplex) with polyelectrolyte dextran sulfate (DXT). Significance: Poor bioavailability of PPZ necessitated the development of fast-dissolving PPZ formulations regardless of delivery routes. Existing fast-dissolving formulations, however, exhibited low PPZ payload. The high-payload PPZ-DXT nanoplex represents an attractive fast-dissolving formulation, as dissolution rate is known to be proportional to payload. Methods: The nanoplex was prepared by electrostatically driven complexation between PPZ and DXT in a simple process that involved only ambient mixing of PPZ and DXT solutions. We investigated the effects of key variables in drug-polyelectrolyte complexation (i.e. pH and charge ratio RDXT/PPZ) on the physical characteristics and preparation efficiency of the nanoplex produced. Subsequently, we characterized the colloidal and amorphous state stabilities, dissolution enhancement, and supersaturation generation of the nanoplex prepared at the optimal condition. Results: The physical characteristics of nanoplex were governed by RDXT/PPZ, while the preparation efficiency was governed by the preparation pH. Nanoplex having size of %80nm, zeta potential of %(-) 60 mV, and payload of %70% (w/w) were prepared at nearly 90% PPZ utilization rate and %60% yield. The nanoplex exhibited superior dissolution than native PPZ in simulated intestinal juice, resulting in high and prolonged apparent solubility with good storage liabilities. Conclusions: The simple yet efficient preparation, excellent physical characteristics, fast dissolution, and high apparent solubility exhibited by the PPZ-DXT nanoplex established its potential as a new bioavailabil- ity enhancement strategy of PPZ. 2020-06-11T02:58:59Z 2020-06-11T02:58:59Z 2017 Journal Article Dong, B., & Hadinoto, K. (2017). Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine. Drug Development and Industrial Pharmacy, 43(6), 996-1002. doi:10.1080/03639045.2017.1287721 0363-9045 https://hdl.handle.net/10356/141825 10.1080/03639045.2017.1287721 6 43 996 1002 en Drug Development and Industrial Pharmacy © 2017 Informa UK Limited, trading as Taylor & Francis Group. All rights reserved.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic Pharmacy
Engineering::Chemical engineering
Amorphization
Supersaturation
spellingShingle Pharmacy
Engineering::Chemical engineering
Amorphization
Supersaturation
Dong, Bingxue
Hadinoto, Kunn
Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine
description Objective: The objective of this study is to develop a new solubility enhancement strategy of anti- psychotic drug – perphenazine (PPZ) – in the form of its amorphous nanoparticle complex (or nanoplex) with polyelectrolyte dextran sulfate (DXT). Significance: Poor bioavailability of PPZ necessitated the development of fast-dissolving PPZ formulations regardless of delivery routes. Existing fast-dissolving formulations, however, exhibited low PPZ payload. The high-payload PPZ-DXT nanoplex represents an attractive fast-dissolving formulation, as dissolution rate is known to be proportional to payload. Methods: The nanoplex was prepared by electrostatically driven complexation between PPZ and DXT in a simple process that involved only ambient mixing of PPZ and DXT solutions. We investigated the effects of key variables in drug-polyelectrolyte complexation (i.e. pH and charge ratio RDXT/PPZ) on the physical characteristics and preparation efficiency of the nanoplex produced. Subsequently, we characterized the colloidal and amorphous state stabilities, dissolution enhancement, and supersaturation generation of the nanoplex prepared at the optimal condition. Results: The physical characteristics of nanoplex were governed by RDXT/PPZ, while the preparation efficiency was governed by the preparation pH. Nanoplex having size of %80nm, zeta potential of %(-) 60 mV, and payload of %70% (w/w) were prepared at nearly 90% PPZ utilization rate and %60% yield. The nanoplex exhibited superior dissolution than native PPZ in simulated intestinal juice, resulting in high and prolonged apparent solubility with good storage liabilities. Conclusions: The simple yet efficient preparation, excellent physical characteristics, fast dissolution, and high apparent solubility exhibited by the PPZ-DXT nanoplex established its potential as a new bioavailabil- ity enhancement strategy of PPZ.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Dong, Bingxue
Hadinoto, Kunn
format Article
author Dong, Bingxue
Hadinoto, Kunn
author_sort Dong, Bingxue
title Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine
title_short Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine
title_full Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine
title_fullStr Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine
title_full_unstemmed Amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine
title_sort amorphous nanoparticle complex of perphenazine and dextran sulfate as a new solubility enhancement strategy of antipsychotic perphenazine
publishDate 2020
url https://hdl.handle.net/10356/141825
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