Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers

Ibrahim Elsayed,1 Aly Ahmed Abdelbary,1 Ahmed Hassen Elshafeey1,21Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutical Sciences, School of Pharmacy, University of Waterloo, ON, CanadaContext: Diacerein (DCN) has low...

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Autores principales:	Elsayed I, Abdelbary AA, Elshafeey AH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3201e967b77d49a2b5d2581f6e3fcfb2
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spelling	oai:doaj.org-article:3201e967b77d49a2b5d2581f6e3fcfb22021-12-02T06:25:50ZNanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers1178-2013https://doaj.org/article/3201e967b77d49a2b5d2581f6e3fcfb22014-06-01T00:00:00Zhttp://www.dovepress.com/nanosizing-of-a-poorly-soluble-drug-technique-optimization-factorial-a-a17224https://doaj.org/toc/1178-2013 Ibrahim Elsayed,1 Aly Ahmed Abdelbary,1 Ahmed Hassen Elshafeey1,21Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutical Sciences, School of Pharmacy, University of Waterloo, ON, CanadaContext: Diacerein (DCN) has low aqueous solubility (3.197 mg/L) and, consequently, low oral bioavailability (35%–56%). To increase both the solubility and dissolution rate of DCN while maintaining its crystalline nature, high pressure homogenization was used but with only a few homogenization cycles preceded by a simple bottom-up technique.Methods: The nanosuspensions of DCN were prepared using a combined bottom-up/top-down technique. Different surfactants – polyvinyl alcohol, sodium deoxycholate, and sodium dodecyl sulfate – with different concentrations were used for the stabilization of the nanosuspensions. Full factorial experimental design was employed to investigate the influence of formulation variables on nanosuspension characteristics using Design-Expert® Software. Particle size (PS), zeta potential, saturation solubility, in vitro dissolution, and drug crystallinity were studied. Moreover, the in vivo performance of the optimized formula was assessed by bioavailability determination in healthy human volunteers.Results: The concentration of surfactant had a significant effect on both the PS and polydispersity index values. The 1% surfactant concentration showed the lowest PS and polydispersity index values compared with other concentrations. Both type and concentration of surfactant had significant effects on the zeta potential. Formula F8 (containing 1% sodium deoxycholate) and Formula F12 (containing 1% sodium dodecyl sulfate) had the highest desirability values (0.952 and 0.927, respectively). Hence, they were selected for further characterization. The saturated solubility and mean dissolution time, in the case of F8 and F12, were significantly higher than the coarse drug powder. Techniques utilized in the nanocrystals’ preparation had no effect on DCN crystalline state. The selected formula (F12) showed a higher bioavailability compared to the reference market product with relative bioavailability of 131.4%.Conclusion: The saturation solubility, in vitro dissolution rate and relative bioavailability of DCN were significantly increased after nanocrystallization. Less time and power consumption were applied by the combination of bottom-up and top-down techniques.Keywords: nanocrystals, high pressure homogenization, diacerein, factorial analysis, pharmacokinetic studyElsayed IAbdelbary AAElshafeey AHDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2943-2953 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Elsayed I Abdelbary AA Elshafeey AH Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers
description	Ibrahim Elsayed,1 Aly Ahmed Abdelbary,1 Ahmed Hassen Elshafeey1,21Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutical Sciences, School of Pharmacy, University of Waterloo, ON, CanadaContext: Diacerein (DCN) has low aqueous solubility (3.197 mg/L) and, consequently, low oral bioavailability (35%–56%). To increase both the solubility and dissolution rate of DCN while maintaining its crystalline nature, high pressure homogenization was used but with only a few homogenization cycles preceded by a simple bottom-up technique.Methods: The nanosuspensions of DCN were prepared using a combined bottom-up/top-down technique. Different surfactants – polyvinyl alcohol, sodium deoxycholate, and sodium dodecyl sulfate – with different concentrations were used for the stabilization of the nanosuspensions. Full factorial experimental design was employed to investigate the influence of formulation variables on nanosuspension characteristics using Design-Expert® Software. Particle size (PS), zeta potential, saturation solubility, in vitro dissolution, and drug crystallinity were studied. Moreover, the in vivo performance of the optimized formula was assessed by bioavailability determination in healthy human volunteers.Results: The concentration of surfactant had a significant effect on both the PS and polydispersity index values. The 1% surfactant concentration showed the lowest PS and polydispersity index values compared with other concentrations. Both type and concentration of surfactant had significant effects on the zeta potential. Formula F8 (containing 1% sodium deoxycholate) and Formula F12 (containing 1% sodium dodecyl sulfate) had the highest desirability values (0.952 and 0.927, respectively). Hence, they were selected for further characterization. The saturated solubility and mean dissolution time, in the case of F8 and F12, were significantly higher than the coarse drug powder. Techniques utilized in the nanocrystals’ preparation had no effect on DCN crystalline state. The selected formula (F12) showed a higher bioavailability compared to the reference market product with relative bioavailability of 131.4%.Conclusion: The saturation solubility, in vitro dissolution rate and relative bioavailability of DCN were significantly increased after nanocrystallization. Less time and power consumption were applied by the combination of bottom-up and top-down techniques.Keywords: nanocrystals, high pressure homogenization, diacerein, factorial analysis, pharmacokinetic study
format	article
author	Elsayed I Abdelbary AA Elshafeey AH
author_facet	Elsayed I Abdelbary AA Elshafeey AH
author_sort	Elsayed I
title	Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers
title_short	Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers
title_full	Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers
title_fullStr	Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers
title_full_unstemmed	Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers
title_sort	nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/3201e967b77d49a2b5d2581f6e3fcfb2
work_keys_str_mv	AT elsayedi nanosizingofapoorlysolubledrugtechniqueoptimizationfactorialanalysisandpharmacokineticstudyinhealthyhumanvolunteers AT abdelbaryaa nanosizingofapoorlysolubledrugtechniqueoptimizationfactorialanalysisandpharmacokineticstudyinhealthyhumanvolunteers AT elshafeeyah nanosizingofapoorlysolubledrugtechniqueoptimizationfactorialanalysisandpharmacokineticstudyinhealthyhumanvolunteers
_version_	1718399924939259904

Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers

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