Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal

Manal A Elsheikh,1 Yosra SR Elnaggar,1 Eman Y Gohar,2 Ossama Y Abdallah11Department of Pharmaceutics, 2Department of Pharmacology and Toxicology, Alexandria University, Alexandria, EgyptAbstract: Raloxifene hydrochloride (RLX) is a selective estrogen-receptor modulator for treatment of osteoporosis...

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Autores principales:	Elsheikh MA, Elnaggar YS, Gohar EY, Abdallah OY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e3f2e141a346498f95f0be9192efc508
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spelling	oai:doaj.org-article:e3f2e141a346498f95f0be9192efc5082021-12-02T00:30:23ZNanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal1176-91141178-2013https://doaj.org/article/e3f2e141a346498f95f0be9192efc5082012-07-01T00:00:00Zhttp://www.dovepress.com/nanoemulsion-liquid-preconcentrates-for-raloxifene-hydrochloride-optim-a10448https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Manal A Elsheikh,1 Yosra SR Elnaggar,1 Eman Y Gohar,2 Ossama Y Abdallah11Department of Pharmaceutics, 2Department of Pharmacology and Toxicology, Alexandria University, Alexandria, EgyptAbstract: Raloxifene hydrochloride (RLX) is a selective estrogen-receptor modulator for treatment of osteoporosis and prevention of breast and endometrial cancer. By virtue of extensive presystemic clearance, RLX bioavailability is only 2%. The current study aimed to tailor and characterize RLX-loaded self-nanoemulsifying drug-delivery systems (SNEDDS) using bioactive excipients affecting drug metabolism. The potential of oral nanocarriers to enhance RLX delivery to endocrine target organs was assessed in fasted and fed female Wistar rats using high-performance liquid chromatography. RLX was loaded in the dissolved and dispersed status in the alkalinized (A-SNEDDS) and nonalkalinized (NA-SNEDDS) systems, respectively. Optimization and assessment relied on solubility studies, emulsification efficiency, phase diagrams, dilution robustness, cloud point, particle size, zeta potential (ZP), polydispersity index (PDI), and transmission electron microscopy. In vitro release was assessed using dialysis bag versus dissolution cup methods. NA-SNEDDS were developed with suitable globule size (38.49 &plusmn; 4.30 nm), ZP (31.70 &plusmn; 3.58 mV), PDI (0.31 &plusmn; 0.02), and cloud point (85&deg;C). A-SNEDDS exhibited good globule size (35 &plusmn; 2.80 nm), adequate PDI (0.28 &plusmn; 0.06), and lower ZP magnitude (-21.20 &plusmn; 3.46 mV). Transmission electron microscopy revealed spherical globules and contended data of size analysis. Release studies demonstrated a nonsignificant enhancement of RLX release from NA-SNEDDS compared to drug suspension with the lowest release shown by A-SNEDDS. A conflicting result was elucidated from in vivo trial. A significant enhancement in RLX uptake by endocrine organs was observed after nanocarrier administration compared to RLX suspension. In vivo studies reflected a poor in vitro/in vivo correlation, recommended nanocarrier administration before meals, and did not reveal any advantage for drug loading in the solubilized form (A-SNEDDS). To conclude, NA-SNEDDS possessed superior in vitro characteristics to A-SNEDDS, with equal in vivo potential. NA-SNEDDS elaborated in this work could successfully double RLX delivery to endocrine target organs, with promising consequences of lower dose and side effects of the drug.Keywords: self-nanoemulsifying drug-delivery system, Biopharmaceutics Drug Disposition Classification System, Cremophor EL, endocrine organs, selective estrogen-receptor modulatorElsheikh MAElnaggar YSGohar EYAbdallah OYDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 3787-3802 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Elsheikh MA Elnaggar YS Gohar EY Abdallah OY Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal
description	Manal A Elsheikh,1 Yosra SR Elnaggar,1 Eman Y Gohar,2 Ossama Y Abdallah11Department of Pharmaceutics, 2Department of Pharmacology and Toxicology, Alexandria University, Alexandria, EgyptAbstract: Raloxifene hydrochloride (RLX) is a selective estrogen-receptor modulator for treatment of osteoporosis and prevention of breast and endometrial cancer. By virtue of extensive presystemic clearance, RLX bioavailability is only 2%. The current study aimed to tailor and characterize RLX-loaded self-nanoemulsifying drug-delivery systems (SNEDDS) using bioactive excipients affecting drug metabolism. The potential of oral nanocarriers to enhance RLX delivery to endocrine target organs was assessed in fasted and fed female Wistar rats using high-performance liquid chromatography. RLX was loaded in the dissolved and dispersed status in the alkalinized (A-SNEDDS) and nonalkalinized (NA-SNEDDS) systems, respectively. Optimization and assessment relied on solubility studies, emulsification efficiency, phase diagrams, dilution robustness, cloud point, particle size, zeta potential (ZP), polydispersity index (PDI), and transmission electron microscopy. In vitro release was assessed using dialysis bag versus dissolution cup methods. NA-SNEDDS were developed with suitable globule size (38.49 &plusmn; 4.30 nm), ZP (31.70 &plusmn; 3.58 mV), PDI (0.31 &plusmn; 0.02), and cloud point (85&deg;C). A-SNEDDS exhibited good globule size (35 &plusmn; 2.80 nm), adequate PDI (0.28 &plusmn; 0.06), and lower ZP magnitude (-21.20 &plusmn; 3.46 mV). Transmission electron microscopy revealed spherical globules and contended data of size analysis. Release studies demonstrated a nonsignificant enhancement of RLX release from NA-SNEDDS compared to drug suspension with the lowest release shown by A-SNEDDS. A conflicting result was elucidated from in vivo trial. A significant enhancement in RLX uptake by endocrine organs was observed after nanocarrier administration compared to RLX suspension. In vivo studies reflected a poor in vitro/in vivo correlation, recommended nanocarrier administration before meals, and did not reveal any advantage for drug loading in the solubilized form (A-SNEDDS). To conclude, NA-SNEDDS possessed superior in vitro characteristics to A-SNEDDS, with equal in vivo potential. NA-SNEDDS elaborated in this work could successfully double RLX delivery to endocrine target organs, with promising consequences of lower dose and side effects of the drug.Keywords: self-nanoemulsifying drug-delivery system, Biopharmaceutics Drug Disposition Classification System, Cremophor EL, endocrine organs, selective estrogen-receptor modulator
format	article
author	Elsheikh MA Elnaggar YS Gohar EY Abdallah OY
author_facet	Elsheikh MA Elnaggar YS Gohar EY Abdallah OY
author_sort	Elsheikh MA
title	Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal
title_short	Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal
title_full	Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal
title_fullStr	Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal
title_full_unstemmed	Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal
title_sort	nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/e3f2e141a346498f95f0be9192efc508
work_keys_str_mv	AT elsheikhma nanoemulsionliquidpreconcentratesforraloxifenehydrochlorideoptimizationandinvivoappraisal AT elnaggarys nanoemulsionliquidpreconcentratesforraloxifenehydrochlorideoptimizationandinvivoappraisal AT goharey nanoemulsionliquidpreconcentratesforraloxifenehydrochlorideoptimizationandinvivoappraisal AT abdallahoy nanoemulsionliquidpreconcentratesforraloxifenehydrochlorideoptimizationandinvivoappraisal
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Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal

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