Preparation and in vivo evaluation of a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system.

Min-Soo Kim,In-Hwan Baek,Gwang-Ho Choo,Eun-Sol Ha

doi:10.3390/ijms160510821

Abstract

The purpose of this study was to prepare a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system (SMEDDS) using hydrophilic additives with high oral bioavailability, and to determine if there was a correlation between the in vitro dissolution data and the in vivo pharmacokinetic parameters of this delivery system in rats. A dutasteride-loaded solid-supersaturatable SMEDDS was generated by adsorption of liquid SMEDDS onto Aerosil 200 colloidal silica using a spray drying process. The dissolution and oral absorption of dutasteride from solid SMEDDS significantly increased after the addition of hydroxypropylmethyl cellulose (HPMC) or Soluplus. Solid SMEDDS/Aerosil 200/Soluplus microparticles had higher oral bioavailability with 6.8- and 5.0-fold higher peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) values, respectively, than that of the equivalent physical mixture. A linear correlation between in vitro dissolution efficiency and in vivo pharmacokinetic parameters was demonstrated for both AUC and Cmax values. Therefore, the preparation of a solid-supersaturatable SMEDDS with HPMC or Soluplus could be a promising formulation strategy to develop novel solid dosage forms of dutasteride.

Highlights

Dutasteride is a 5-α reductase inhibitor (Figure 1), which is used to treat benign prostatic hyperplasia [1].In GlaxoSmithKline’s commercial formulation, Avodart®, dutasteride’s poor aqueous solubility (
To develop a solid dutasteride dosage form with high oral bioavailability, we evaluated various formulations, such as Eudragit E nanosuspension, hydroxypropyl-β-cyclodextrin (HP-β-CD) nanostructures, silica nanomatrices, self-microemulsifying drug delivery systems (SMEDDS), and solid dispersions [2,3,4,5,6,7]
We developed and optimized a dutasteride-loaded SMEDDS formulation containing Capryol 90, Cremophor EL, and Transcutol HP, based on a D-optimal mixture design [5]

Summary

Introduction

Dutasteride is a 5-α reductase inhibitor (Figure 1), which is used to treat benign prostatic hyperplasia [1].In GlaxoSmithKline’s commercial formulation, Avodart®, dutasteride’s poor aqueous solubility (

Objectives

Results

Conclusion