Open AccessPreparation and evaluation of a novel solid dispersion using leucine as carrier
Author(s) -
Xia Xiaojing,
Tan Zeng,
Fan Yaru,
Hu Ying,
Deng Jin
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13200
Subject(s) - bioavailability , differential scanning calorimetry , chromatography , chemistry , absorption (acoustics) , pharmacokinetics , dissolution , materials science , nuclear chemistry , pharmacology , medicine , organic chemistry , physics , composite material , thermodynamics
Objective The aim of this study was to develop a novel formulation of oleanolic acid (OA) solid dispersion (SD), using leucine (Leu) as the carrier to improve OA oral bioavailability. Methods The OA‐Leu SD was prepared by solvent evaporation and was evaluated in vitro using differential scanning calorimetry, X‐ray powder diffraction, scanning electron microscopy, flowability, hygroscopicity and dissolution test. The stability of the SD was evaluated using accelerated testing. In vivo pharmacokinetic tests were performed in male Sprague Dawley rats using a liquid chromatography tandem‐mass spectrometry bioanalytical method. Key findings OA‐Leu SD was successfully prepared, and OA was mostly in an amorphous state. More than 80% of OA could dissolve in OA‐Leu SD in 20 min, while only 13.4% of free OA dissolved. The powder flow of OA‐Leu SD was clearly improved compared with free OA and its moisture absorption was 3.4%. The accelerated testing further demonstrated that SD could maintain OA in an amorphous state at 40 °C for 6 months. OA‐Leu SD showed higher relative oral bioavailability (189.7%) than free OA in rats. Conclusions Using Leu as a carrier produced a SD with good flowability, low hygroscopicity and high bioavailability.