Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy

Mallesh Kurakula,1 AM El-Helw,2 Tariq R Sobahi,1 Magdy Y Abdelaal11Polymer Research Lab, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia...

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Autores principales:	Kurakula M, El-Helw AM, Sobahi TR, Abdelaal MY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/eab89bc1dae34e16abd97ed60c841688
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spelling	oai:doaj.org-article:eab89bc1dae34e16abd97ed60c8416882021-12-02T07:37:01ZChitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy1178-2013https://doaj.org/article/eab89bc1dae34e16abd97ed60c8416882015-01-01T00:00:00Zhttp://www.dovepress.com/chitosan-based-atorvastatin-nanocrystals-effect-of-cationic-charge-on--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Mallesh Kurakula,1 AM El-Helw,2 Tariq R Sobahi,1 Magdy Y Abdelaal11Polymer Research Lab, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaAbstract: Cationic charged chitosan as stabilizer was evaluated in preparation of nanocrystals using probe sonication method. The influence of cationic charge densities of chitosan (low CSL, medium CSM, high CSH molecular weights) and Labrasol® in solubility enhancement and modifying the release was investigated, using atorvastatin (ATR) as poorly soluble model drug. Compared to CSM and CSH; low cationic charge of CSL acted as both electrostatic and steric stabilizer by significant size reduction to 394 nm with charge of 21.5 meV. Solubility of ATR-CSL increased to 60-fold relative to pure ATR and ATR-L. Nanocrystals were characterized for physiochemical properties. Scanning electron microscopy revealed scaffold-like structures with high surface area. X-ray powder diffractometry and differential scanning calorimetry revealed crystalline to slight amorphous state changes after cationic charge size reduction. Fourier transform-infrared spectra indicated no potent drug-excipient interactions. The enhanced dissolution profile of ATR-CSL indicates that sustained release was achieved compared with ATR-L and Lipitor®. Anti-hyperlipidemic performance was pH dependent where ATR-CSL exhibited 2.5-fold higher efficacy at pH 5 compared to pH 6 and Lipitor®. Stability studies indicated marked changes in size and charge for ATR-L compared to ATR-CSL exemplifying importance of the stabilizer. Therefore, nanocrystals developed with CSL as a stabilizer is a promising choice to enhance dissolution, stability, and in-vivo efficacy of major Biopharmaceutical Classification System II/IV drugs.Keywords: atorvastatin, anti-hyperlipidemia, chitosan, cationic charge, stability, nanocrystals, in-vivo efficacyKurakula MEl-Helw AMSobahi TRAbdelaal MYDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 321-334 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Kurakula M El-Helw AM Sobahi TR Abdelaal MY Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy
description	Mallesh Kurakula,1 AM El-Helw,2 Tariq R Sobahi,1 Magdy Y Abdelaal11Polymer Research Lab, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaAbstract: Cationic charged chitosan as stabilizer was evaluated in preparation of nanocrystals using probe sonication method. The influence of cationic charge densities of chitosan (low CSL, medium CSM, high CSH molecular weights) and Labrasol® in solubility enhancement and modifying the release was investigated, using atorvastatin (ATR) as poorly soluble model drug. Compared to CSM and CSH; low cationic charge of CSL acted as both electrostatic and steric stabilizer by significant size reduction to 394 nm with charge of 21.5 meV. Solubility of ATR-CSL increased to 60-fold relative to pure ATR and ATR-L. Nanocrystals were characterized for physiochemical properties. Scanning electron microscopy revealed scaffold-like structures with high surface area. X-ray powder diffractometry and differential scanning calorimetry revealed crystalline to slight amorphous state changes after cationic charge size reduction. Fourier transform-infrared spectra indicated no potent drug-excipient interactions. The enhanced dissolution profile of ATR-CSL indicates that sustained release was achieved compared with ATR-L and Lipitor®. Anti-hyperlipidemic performance was pH dependent where ATR-CSL exhibited 2.5-fold higher efficacy at pH 5 compared to pH 6 and Lipitor®. Stability studies indicated marked changes in size and charge for ATR-L compared to ATR-CSL exemplifying importance of the stabilizer. Therefore, nanocrystals developed with CSL as a stabilizer is a promising choice to enhance dissolution, stability, and in-vivo efficacy of major Biopharmaceutical Classification System II/IV drugs.Keywords: atorvastatin, anti-hyperlipidemia, chitosan, cationic charge, stability, nanocrystals, in-vivo efficacy
format	article
author	Kurakula M El-Helw AM Sobahi TR Abdelaal MY
author_facet	Kurakula M El-Helw AM Sobahi TR Abdelaal MY
author_sort	Kurakula M
title	Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy
title_short	Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy
title_full	Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy
title_fullStr	Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy
title_full_unstemmed	Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy
title_sort	chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/eab89bc1dae34e16abd97ed60c841688
work_keys_str_mv	AT kurakulam chitosanbasedatorvastatinnanocrystalseffectofcationicchargeonparticlesizeformulationstabilityandinvivoefficacy AT elhelwam chitosanbasedatorvastatinnanocrystalseffectofcationicchargeonparticlesizeformulationstabilityandinvivoefficacy AT sobahitr chitosanbasedatorvastatinnanocrystalseffectofcationicchargeonparticlesizeformulationstabilityandinvivoefficacy AT abdelaalmy chitosanbasedatorvastatinnanocrystalseffectofcationicchargeonparticlesizeformulationstabilityandinvivoefficacy
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Chitosan based atorvastatin nanocrystals: effect of cationic charge on particle size, formulation stability, and in-vivo efficacy

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