Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide

Yueqin Ma,1,2,* Yang Yang,2,* Jin Xie,1 Junnan Xu,1 Pengfei Yue,1 Ming Yang1 1Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, 2Department of Medicine and Pharmacy, 94th Hospital of People’s...

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Autores principales:	Ma Y, Yang Y, Xie J, Xu J, Yue P, Yang M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	nanocrystals based solid dispersion nanocrystals andrographolide superdisintegrant dissolution bioavailability Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/784f94eab7bd42ddac3e9570b9c4b559
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spelling	oai:doaj.org-article:784f94eab7bd42ddac3e9570b9c4b5592021-12-02T00:40:30ZNovel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide1178-2013https://doaj.org/article/784f94eab7bd42ddac3e9570b9c4b5592018-06-01T00:00:00Zhttps://www.dovepress.com/novel-nanocrystal-based-solid-dispersion-with-high-drug-loading-enhanc-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yueqin Ma,1,2,* Yang Yang,2,* Jin Xie,1 Junnan Xu,1 Pengfei Yue,1 Ming Yang1 1Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, 2Department of Medicine and Pharmacy, 94th Hospital of People’s Liberation Army, Nanchang, Jiangxi, 330002, China *These authors contributed equally to this work Objective: The current study sought to design a quickly dissolving, high drug loading nanocrystal-based solid dispersion (NC-SD) in order to improve the dissolution of poorly soluble drugs. Methods: The NC-SD was prepared by means of combination of homogenization and spray-drying. Polymer hydroxypropylmethylcellulose (HPMC) was used as baseline dispersant for NC-SD of the model drug – andrographolide (AG). Three superdisintegrants cohomogenized with HPMC were used as codispersant for AG-NC-SD and compared to common water-soluble dispersants – mannitol and lactose. The dissolution characterization and oral bioavailability of AG-NC-SD were evaluated. Results: The AG-NC-SD with the higher concentration of HPMC exhibited fast dissolution due to the enhanced wettability of HPMC. The water-soluble codispersants (mannitol and lactose) did not completely prevent AG-NC from aggregation during spray-drying. To achieve much faster AG release, cohomogenized superdisintegrants at a level of 20% must be used along with 25% HPMC. Compared with water-soluble dispersants like mannitol and lactose, superdisintegrants with high swelling capacity were much more effective dispersants for enhancing fast redispersion/dissolution of AG-NC-SD via a swelling-triggered erosion/disintegration mechanism. Surfactant-free AG-NC-SD with 15% cohomogenized sodium carboxymethyl starch combined with 15% HPMC and 10% lactose enhanced the dissolution further, without comprising drug loading, exhibited a barely compromised dissolution rate compared to precursor NC suspensions (f2>50), and possessed drug loading up to 67.83%±1.26%. The pharmacokinetics results also demonstrated that the AG-NC-SD significantly improved the bioavailability in vivo of AG (P<0.05), compared with to the coarse AG. Conclusion: This study illustrates that a quickly dissolving, high drug load, surfactant-free NC-SD can be prepared by using a superdisintegrant as codispersant, and provides a feasible strategy to improve the oral bioavailability of poorly soluble drugs. Keywords: nanocrystal-based solid dispersion, nanocrystals, andrographolide, superdisintegrant, dissolution, bioavailabilityMa YYang YXie JXu JYue PYang MDove Medical Pressarticlenanocrystals based solid dispersionnanocrystalsandrographolidesuperdisintegrantdissolutionbioavailabilityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3763-3779 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanocrystals based solid dispersion nanocrystals andrographolide superdisintegrant dissolution bioavailability Medicine (General) R5-920
spellingShingle	nanocrystals based solid dispersion nanocrystals andrographolide superdisintegrant dissolution bioavailability Medicine (General) R5-920 Ma Y Yang Y Xie J Xu J Yue P Yang M Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide
description	Yueqin Ma,1,2,* Yang Yang,2,* Jin Xie,1 Junnan Xu,1 Pengfei Yue,1 Ming Yang1 1Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, 2Department of Medicine and Pharmacy, 94th Hospital of People’s Liberation Army, Nanchang, Jiangxi, 330002, China *These authors contributed equally to this work Objective: The current study sought to design a quickly dissolving, high drug loading nanocrystal-based solid dispersion (NC-SD) in order to improve the dissolution of poorly soluble drugs. Methods: The NC-SD was prepared by means of combination of homogenization and spray-drying. Polymer hydroxypropylmethylcellulose (HPMC) was used as baseline dispersant for NC-SD of the model drug – andrographolide (AG). Three superdisintegrants cohomogenized with HPMC were used as codispersant for AG-NC-SD and compared to common water-soluble dispersants – mannitol and lactose. The dissolution characterization and oral bioavailability of AG-NC-SD were evaluated. Results: The AG-NC-SD with the higher concentration of HPMC exhibited fast dissolution due to the enhanced wettability of HPMC. The water-soluble codispersants (mannitol and lactose) did not completely prevent AG-NC from aggregation during spray-drying. To achieve much faster AG release, cohomogenized superdisintegrants at a level of 20% must be used along with 25% HPMC. Compared with water-soluble dispersants like mannitol and lactose, superdisintegrants with high swelling capacity were much more effective dispersants for enhancing fast redispersion/dissolution of AG-NC-SD via a swelling-triggered erosion/disintegration mechanism. Surfactant-free AG-NC-SD with 15% cohomogenized sodium carboxymethyl starch combined with 15% HPMC and 10% lactose enhanced the dissolution further, without comprising drug loading, exhibited a barely compromised dissolution rate compared to precursor NC suspensions (f2>50), and possessed drug loading up to 67.83%±1.26%. The pharmacokinetics results also demonstrated that the AG-NC-SD significantly improved the bioavailability in vivo of AG (P<0.05), compared with to the coarse AG. Conclusion: This study illustrates that a quickly dissolving, high drug load, surfactant-free NC-SD can be prepared by using a superdisintegrant as codispersant, and provides a feasible strategy to improve the oral bioavailability of poorly soluble drugs. Keywords: nanocrystal-based solid dispersion, nanocrystals, andrographolide, superdisintegrant, dissolution, bioavailability
format	article
author	Ma Y Yang Y Xie J Xu J Yue P Yang M
author_facet	Ma Y Yang Y Xie J Xu J Yue P Yang M
author_sort	Ma Y
title	Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide
title_short	Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide
title_full	Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide
title_fullStr	Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide
title_full_unstemmed	Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide
title_sort	novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/784f94eab7bd42ddac3e9570b9c4b559
work_keys_str_mv	AT may novelnanocrystalbasedsoliddispersionwithhighdrugloadingenhanceddissolutionandbioavailabilityofandrographolide AT yangy novelnanocrystalbasedsoliddispersionwithhighdrugloadingenhanceddissolutionandbioavailabilityofandrographolide AT xiej novelnanocrystalbasedsoliddispersionwithhighdrugloadingenhanceddissolutionandbioavailabilityofandrographolide AT xuj novelnanocrystalbasedsoliddispersionwithhighdrugloadingenhanceddissolutionandbioavailabilityofandrographolide AT yuep novelnanocrystalbasedsoliddispersionwithhighdrugloadingenhanceddissolutionandbioavailabilityofandrographolide AT yangm novelnanocrystalbasedsoliddispersionwithhighdrugloadingenhanceddissolutionandbioavailabilityofandrographolide
_version_	1718403562117005312

Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide

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