Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E

Abstract

Abstract:The present study aimed to investigate the effect of Eudragit ® E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1) solid dispersion had a maximum solubility of 196.7 μg/mL within 0.5 h that gradually decreased to 173.4 μg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1) solid dispersion in simulated gastric fluid (pH 1.2), owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1) solid dispersion, the sirolimus/E-SD/TPGS (1/8/1) solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited OPEN ACCESSMolecules 2015, 20 9497 the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC). Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications.

Effect of Polymer Type on the Dissolution Profile of a Solid Dispersion of Cilostazol

“…Eudragit E powder neutralized with HCl was manufactured by using an SD 1000 laboratory scale spray dryer (Eyela, Tokyo, Japan), as previously reported . Eudragit E (200 g) was dissolved in a solution of HCl (147 g, 10% w/v) and water (1053 g).…”

“…34 Eudragit E (200 g) was dissolved in a solution of HCl (147 g, 10% w/v) and water (1053 g). Eudragit E powder neutralized with HCl was manufactured by using an SD 1000 laboratory scale spray dryer (Eyela, Tokyo, Japan), as previously reported.…”

Influence of Hydroxypropylmethylcellulose and Sodium Lauryl Sulfate on the Solubility and Dissolution of Sirolimus in Solvent‐evaporated Solid Dispersions

“…A solid dispersion system can boost significantly the aqueous solubility and dissolution of BCS class II chemicals . There were various solubility enhancing systems applied, such as supersaturation, supercritical antisolvent process, self‐microemulsifying drug delivery system, and micelles, to improve aqueous solubility and dissolution of poorly water‐soluble sirolimus. A prevalent technique for preparing dry powder of solid dispersions from liquid phase is spray drying because it is a one‐step process that gives sufficient output and is easy to scale up .…”

Characterization, Molecular Docking, and In Vitro Dissolution Studies of Solid Dispersions of 20(S)-Protopanaxadiol

“…Furthermore, SD can be formulated in oral solid preparations, which are more acceptable to patients than liquid products produced through solubilization [ 51 , 52 ]. Therefore, SD has been widely used to develop new drugs as one of the most effective formulations to improve the solubility and bioavailability of water-insoluble drugs [ 53 , 54 ]. Identification of drugs dispersion state in SD is essential.…”