Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement

Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Parikh A [verfasserIn] Kathawala K [verfasserIn] Tan CC [verfasserIn] Garg S [verfasserIn] Zhou XF [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	Edaravone Soluplus Nanotechnology oral bioavailability Metabolism Permeability

Übergeordnetes Werk:	In: Drug Design, Development and Therapy - Dove Medical Press, 2008, (2018), Seite 2051-2069
Übergeordnetes Werk:	year:2018 ; pages:2051-2069

Links:	Link aufrufen Link aufrufen Journal toc

Katalog-ID:	DOAJ011713410

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520			\|a Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability
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allfields	(DE-627)DOAJ011713410 (DE-599)DOAJ695780922a7c413b9d46c85d35cde358 DE-627 ger DE-627 rakwb eng RM1-950 Parikh A verfasserin aut Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability Edaravone Soluplus Nanotechnology oral bioavailability Metabolism Permeability Therapeutics. Pharmacology Kathawala K verfasserin aut Tan CC verfasserin aut Garg S verfasserin aut Zhou XF verfasserin aut In Drug Design, Development and Therapy Dove Medical Press, 2008 (2018), Seite 2051-2069 (DE-627)578533138 (DE-600)2451346-5 11778881 nnns year:2018 pages:2051-2069 https://doaj.org/article/695780922a7c413b9d46c85d35cde358 kostenfrei https://www.dovepress.com/self-nanomicellizing-solid-dispersion-of-edaravone-part-i-oral-bioavai-peer-reviewed-article-DDDT kostenfrei https://doaj.org/toc/1177-8881 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2018 2051-2069
spelling	(DE-627)DOAJ011713410 (DE-599)DOAJ695780922a7c413b9d46c85d35cde358 DE-627 ger DE-627 rakwb eng RM1-950 Parikh A verfasserin aut Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability Edaravone Soluplus Nanotechnology oral bioavailability Metabolism Permeability Therapeutics. Pharmacology Kathawala K verfasserin aut Tan CC verfasserin aut Garg S verfasserin aut Zhou XF verfasserin aut In Drug Design, Development and Therapy Dove Medical Press, 2008 (2018), Seite 2051-2069 (DE-627)578533138 (DE-600)2451346-5 11778881 nnns year:2018 pages:2051-2069 https://doaj.org/article/695780922a7c413b9d46c85d35cde358 kostenfrei https://www.dovepress.com/self-nanomicellizing-solid-dispersion-of-edaravone-part-i-oral-bioavai-peer-reviewed-article-DDDT kostenfrei https://doaj.org/toc/1177-8881 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2018 2051-2069
allfields_unstemmed	(DE-627)DOAJ011713410 (DE-599)DOAJ695780922a7c413b9d46c85d35cde358 DE-627 ger DE-627 rakwb eng RM1-950 Parikh A verfasserin aut Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability Edaravone Soluplus Nanotechnology oral bioavailability Metabolism Permeability Therapeutics. Pharmacology Kathawala K verfasserin aut Tan CC verfasserin aut Garg S verfasserin aut Zhou XF verfasserin aut In Drug Design, Development and Therapy Dove Medical Press, 2008 (2018), Seite 2051-2069 (DE-627)578533138 (DE-600)2451346-5 11778881 nnns year:2018 pages:2051-2069 https://doaj.org/article/695780922a7c413b9d46c85d35cde358 kostenfrei https://www.dovepress.com/self-nanomicellizing-solid-dispersion-of-edaravone-part-i-oral-bioavai-peer-reviewed-article-DDDT kostenfrei https://doaj.org/toc/1177-8881 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2018 2051-2069
allfieldsGer	(DE-627)DOAJ011713410 (DE-599)DOAJ695780922a7c413b9d46c85d35cde358 DE-627 ger DE-627 rakwb eng RM1-950 Parikh A verfasserin aut Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability Edaravone Soluplus Nanotechnology oral bioavailability Metabolism Permeability Therapeutics. Pharmacology Kathawala K verfasserin aut Tan CC verfasserin aut Garg S verfasserin aut Zhou XF verfasserin aut In Drug Design, Development and Therapy Dove Medical Press, 2008 (2018), Seite 2051-2069 (DE-627)578533138 (DE-600)2451346-5 11778881 nnns year:2018 pages:2051-2069 https://doaj.org/article/695780922a7c413b9d46c85d35cde358 kostenfrei https://www.dovepress.com/self-nanomicellizing-solid-dispersion-of-edaravone-part-i-oral-bioavai-peer-reviewed-article-DDDT kostenfrei https://doaj.org/toc/1177-8881 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2018 2051-2069
allfieldsSound	(DE-627)DOAJ011713410 (DE-599)DOAJ695780922a7c413b9d46c85d35cde358 DE-627 ger DE-627 rakwb eng RM1-950 Parikh A verfasserin aut Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability Edaravone Soluplus Nanotechnology oral bioavailability Metabolism Permeability Therapeutics. Pharmacology Kathawala K verfasserin aut Tan CC verfasserin aut Garg S verfasserin aut Zhou XF verfasserin aut In Drug Design, Development and Therapy Dove Medical Press, 2008 (2018), Seite 2051-2069 (DE-627)578533138 (DE-600)2451346-5 11778881 nnns year:2018 pages:2051-2069 https://doaj.org/article/695780922a7c413b9d46c85d35cde358 kostenfrei https://www.dovepress.com/self-nanomicellizing-solid-dispersion-of-edaravone-part-i-oral-bioavai-peer-reviewed-article-DDDT kostenfrei https://doaj.org/toc/1177-8881 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2018 2051-2069
language	English
source	In Drug Design, Development and Therapy (2018), Seite 2051-2069 year:2018 pages:2051-2069
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spellingShingle	Parikh A misc RM1-950 misc Edaravone misc Soluplus misc Nanotechnology misc oral bioavailability misc Metabolism misc Permeability misc Therapeutics. Pharmacology Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement
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topic	misc RM1-950 misc Edaravone misc Soluplus misc Nanotechnology misc oral bioavailability misc Metabolism misc Permeability misc Therapeutics. Pharmacology
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title	Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement
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title_full	Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement
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author_browse	Parikh A Kathawala K Tan CC Garg S Zhou XF
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title_sort	self-nanomicellizing solid dispersion of edaravone: part i – oral bioavailability improvement
callnumber	RM1-950
title_auth	Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement
abstract	Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability
abstractGer	Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability
abstract_unstemmed	Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Background: Edaravone (EDR) is known for its free radical scavenging, antiapoptotic, antinecrotic, and anticytokine effects in neurological and non-neurological diseases. It is currently available clinically as Radicava® and Radicut®, intravenous medications, recently approved for the treatment of amyotrophic lateral sclerosis and cerebral infarction. However, the oral use of EDR is still restricted by its poor oral bioavailability (BA) due to poor aqueous solubility, stability, rapid metabolism, and low permeability. The present study reports the development of novel EDR formulation (NEF) using self-nanomicellizing solid dispersion (SNMSD) strategy with the aim to enable its oral use. Materials and methods: The selection of a suitable carrier for the development of NEF was performed based on the miscibility study. The optimization of EDR-to-carrier ratio was conducted via kinetic solubility study after preparing SNMSDs using solvent evaporation technique. The drug–polymer carrier interaction and self-nanomicellizing properties of NEF were investigated with advanced characterization studies. In vitro permeation, metabolism, and dissolution study was carried out to examine the effect of the presence of a carrier on physicochemical properties of EDR. Additionally, the dose-dependent pharmacokinetic study of NEF was conducted and compared with the EDR suspension. Results: Soluplus® (SOL) as a carrier was selected based on the potential for improving aqueous solubility. The NEF containing EDR and SOL (1:5) resulted in the highest enhancement in aqueous solubility (17.53-fold) due to amorphization, hydrogen bonding interaction, and micellization. Moreover, the NEF demonstrated significant improvement in metabolism, permeability, and dissolution profile of EDR. Furthermore, the oral BA of NEF showed 10.2-, 16.1-, and 14.8-fold enhancement compared to EDR suspension at 46, 138, and 414 µmol/kg doses. Conclusion: The results demonstrated that SNMSD strategy could serve as a promising way to enhance EDR oral BA and NEF could be a potential candidate for the treatment of diseases in which oxidative stress plays a key role in their pathogenesis. Keywords: edaravone, Soluplus®, nanotechnology, oral bioavailability, metabolism, permeability
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title_short	Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement
url	https://doaj.org/article/695780922a7c413b9d46c85d35cde358 https://www.dovepress.com/self-nanomicellizing-solid-dispersion-of-edaravone-part-i-oral-bioavai-peer-reviewed-article-DDDT https://doaj.org/toc/1177-8881
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