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Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process

In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersio...

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Autores principales: Ha, Eun-Sol, Kim, Jeong-Soo, Baek, In-hwan, Yoo, Jin-Wook, Jung, Yunjin, Moon, Hyung Ryong, Kim, Min-Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531043/
https://www.ncbi.nlm.nih.gov/pubmed/26345723
http://dx.doi.org/10.2147/DDDT.S90706
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author Ha, Eun-Sol
Kim, Jeong-Soo
Baek, In-hwan
Yoo, Jin-Wook
Jung, Yunjin
Moon, Hyung Ryong
Kim, Min-Soo
author_facet Ha, Eun-Sol
Kim, Jeong-Soo
Baek, In-hwan
Yoo, Jin-Wook
Jung, Yunjin
Moon, Hyung Ryong
Kim, Min-Soo
author_sort Ha, Eun-Sol
collection PubMed
description In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. Powder X-ray diffraction and differential scanning calorimetry measurements showed that megestrol acetate was present in an amorphous or molecular dispersion state within the solid dispersion nanoparticles. Hydroxypropylmethyl cellulose (HPMC) solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by D-α-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0–24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate.
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spelling pubmed-45310432015-09-04 Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process Ha, Eun-Sol Kim, Jeong-Soo Baek, In-hwan Yoo, Jin-Wook Jung, Yunjin Moon, Hyung Ryong Kim, Min-Soo Drug Des Devel Ther Original Research In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. Powder X-ray diffraction and differential scanning calorimetry measurements showed that megestrol acetate was present in an amorphous or molecular dispersion state within the solid dispersion nanoparticles. Hydroxypropylmethyl cellulose (HPMC) solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by D-α-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0–24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate. Dove Medical Press 2015-08-04 /pmc/articles/PMC4531043/ /pubmed/26345723 http://dx.doi.org/10.2147/DDDT.S90706 Text en © 2015 Ha et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Ha, Eun-Sol
Kim, Jeong-Soo
Baek, In-hwan
Yoo, Jin-Wook
Jung, Yunjin
Moon, Hyung Ryong
Kim, Min-Soo
Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process
title Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process
title_full Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process
title_fullStr Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process
title_full_unstemmed Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process
title_short Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process
title_sort development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531043/
https://www.ncbi.nlm.nih.gov/pubmed/26345723
http://dx.doi.org/10.2147/DDDT.S90706
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