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Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures

Authors Kim MS

Received 5 March 2013

Accepted for publication 23 April 2013

Published 20 May 2013 Volume 2013:8(1) Pages 2029—2039

DOI https://doi.org/10.2147/IJN.S44795

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Min-Soo Kim

Department of Pharmaceutical Engineering, Inje University, Gimhae, Gyeongnam, Republic of Korea

Abstract: The objectives of this study were to develop a novel solid dutasteride formulation with improved physicochemical properties and oral bioavailability, and to examine the correlation between its in vitro dissolution and in vivo pharmacokinetic parameters. Hydroxypropyl-β-cyclodextrin (HP-β-CD) nanostructures with or without hydrophilic additives were manufactured using the supercritical antisolvent process. The dutasteride-loaded HP-β-CD nanoparticles formed aggregates with a mean particle size of less than 160 nm and a specific surface area greater than 100 m2/g. Increases in the supersaturation and dissolution rate for dutasteride were dependent on the type of additive; increases in maximum solubility and extended supersaturation were observed in dutasteride-loaded HP-β-CD nanostructures with hydroxypropylmethyl cellulose, whereas the dissolution rate was the highest for nanostructures containing d-α-tocopheryl polyethylene glycol 1000 succinate. In rats, the oral bioavailability of dutasteride increased with the supersaturation induced by the HP-β-CD nanostructures. In addition, compared with the in vitro drug release rate, the in vivo pharmacokinetic parameters were more closely correlated with in vitro parameters related to supersaturation (solubility). Further, the bioavailability of the dutasteride-loaded HP-β-CD nanostructures with hydroxypropylmethyl cellulose was similar to that of the commercially available soft gelatin capsule (Avodart®). In conclusion, preparation of dutasteride-loaded HP-β-CD nanostructures using the supercritical antisolvent process affords a viable alternative solid dosage form for dutasteride.

Keywords: solubility, bioavailability, dutasteride, nanostructure, supercritical antisolvent

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