Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability

Shujie Guo,1 Kevin Pham,2 Diana Li,2 Scott R Penzak,3 Xiaowei Dong2 1State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pharmaceutical Sc...

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Autores principales:	Guo S, Pham K, Li D, Penzak SR, Dong X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	ritonavir pediatric formulation taste pharmacokinetics lipid formulation drug loading Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/cab3a82c1cb24b7ea3a062bfbe94d4bb
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spelling	oai:doaj.org-article:cab3a82c1cb24b7ea3a062bfbe94d4bb2021-12-02T01:46:45ZNovel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability1178-2013https://doaj.org/article/cab3a82c1cb24b7ea3a062bfbe94d4bb2016-04-01T00:00:00Zhttps://www.dovepress.com/novel-in-situ-self-assembly-nanoparticles-for-formulating-a-poorly-wat-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shujie Guo,1 Kevin Pham,2 Diana Li,2 Scott R Penzak,3 Xiaowei Dong2 1State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pharmaceutical Sciences, 3Department of Pharmacotherapy, University of North Texas Health Science Center, Fort Worth, TX, USA Purpose: The purpose of this study was to develop a novel lipid-based nanotechnology to formulate poorly water-soluble drugs in oral solid granules to improve stability, palatability, and bioavailability. Materials and methods: In one method, we prepared ritonavir (RTV) nanoparticles (NPs) by a microemulsion-precursor method and then converted the RTV NPs to solid granules by wet granulation to produce RTV NP-containing granules. In the other innovative method, we did not use water in the formulation preparation, and discovered novel in situ self-assembly nanoparticles (ISNPs). We prepared RTV ISNP granules that did not initially contain NPs, but spontaneously produced RTV ISNPs when the granules were introduced to water with gentle agitation. We fully characterized these RTV nanoformulations. We also used rats to test the bioavailability of RTV ISNP granules. Finally, an Astree electronic tongue was used to assess the taste of the RTV ISNP granules. Results: RTV NP-containing granules only had about 1% drug loading of RTV in the solid granules. In contrast, RTV ISNP granules achieved over 16% drug loading and were stable at room temperature over 24 weeks. RTV ISNPs had particle size between 160 nm and 300 nm with narrow size distribution. RTV ISNPs were stable in simulated gastric fluid for 2 hours and in simulated intestinal fluid for another 6 hours. The data from the electronic tongue showed that the RTV ISNP granules were similar in taste to blank ISNP granules, but were much different from RTV solution. RTV ISNP granules increased RTV bioavailability over 2.5-fold compared to RTV solution. Conclusion: We successfully discovered and developed novel ISNPs to manufacture RTV ISNP granules that were reconstitutable, stable, and palatable, and improved RTV bioavailability. The novel ISNP nanotechnology is a platform to manufacture oral solid dosage forms for poorly water-soluble drugs, especially for pediatric formulation development. Keywords: ritonavir, pediatric formulation, taste, pharmacokinetics, lipid formulation, drug loadingGuo SPham KLi DPenzak SRDong XDove Medical Pressarticleritonavirpediatric formulationtastepharmacokineticslipid formulationdrug loadingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1451-1460 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	ritonavir pediatric formulation taste pharmacokinetics lipid formulation drug loading Medicine (General) R5-920
spellingShingle	ritonavir pediatric formulation taste pharmacokinetics lipid formulation drug loading Medicine (General) R5-920 Guo S Pham K Li D Penzak SR Dong X Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability
description	Shujie Guo,1 Kevin Pham,2 Diana Li,2 Scott R Penzak,3 Xiaowei Dong2 1State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pharmaceutical Sciences, 3Department of Pharmacotherapy, University of North Texas Health Science Center, Fort Worth, TX, USA Purpose: The purpose of this study was to develop a novel lipid-based nanotechnology to formulate poorly water-soluble drugs in oral solid granules to improve stability, palatability, and bioavailability. Materials and methods: In one method, we prepared ritonavir (RTV) nanoparticles (NPs) by a microemulsion-precursor method and then converted the RTV NPs to solid granules by wet granulation to produce RTV NP-containing granules. In the other innovative method, we did not use water in the formulation preparation, and discovered novel in situ self-assembly nanoparticles (ISNPs). We prepared RTV ISNP granules that did not initially contain NPs, but spontaneously produced RTV ISNPs when the granules were introduced to water with gentle agitation. We fully characterized these RTV nanoformulations. We also used rats to test the bioavailability of RTV ISNP granules. Finally, an Astree electronic tongue was used to assess the taste of the RTV ISNP granules. Results: RTV NP-containing granules only had about 1% drug loading of RTV in the solid granules. In contrast, RTV ISNP granules achieved over 16% drug loading and were stable at room temperature over 24 weeks. RTV ISNPs had particle size between 160 nm and 300 nm with narrow size distribution. RTV ISNPs were stable in simulated gastric fluid for 2 hours and in simulated intestinal fluid for another 6 hours. The data from the electronic tongue showed that the RTV ISNP granules were similar in taste to blank ISNP granules, but were much different from RTV solution. RTV ISNP granules increased RTV bioavailability over 2.5-fold compared to RTV solution. Conclusion: We successfully discovered and developed novel ISNPs to manufacture RTV ISNP granules that were reconstitutable, stable, and palatable, and improved RTV bioavailability. The novel ISNP nanotechnology is a platform to manufacture oral solid dosage forms for poorly water-soluble drugs, especially for pediatric formulation development. Keywords: ritonavir, pediatric formulation, taste, pharmacokinetics, lipid formulation, drug loading
format	article
author	Guo S Pham K Li D Penzak SR Dong X
author_facet	Guo S Pham K Li D Penzak SR Dong X
author_sort	Guo S
title	Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability
title_short	Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability
title_full	Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability
title_fullStr	Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability
title_full_unstemmed	Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability
title_sort	novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/cab3a82c1cb24b7ea3a062bfbe94d4bb
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Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and&nbsp;bioavailability

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Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability