Amorphous solid dispersion preparation via coprecipitation improves the dissolution, oral bioavailability, and intestinal health enhancement properties of magnolol

Magnolol (MAG) is a multifunctional plant polyphenol with anti-inflammatory, antibacterial, antioxidant and antitumor properties. In poultry, it has been shown to improve growth performance, antioxidant, immune functions and intestinal health. However, its applications are limited by poor solubility and low oral bioavailability. This study aimed at improving the water solubility of MAG through solid dispersion and investigating its effects in Arbor Acre (AA) broilers. Hydroxypropyl methylcellulose succinic acid (HPMCAS) was used as a carrier to prepare magnolol solid dispersions (MAG-HPMCAS SD) via antisolvent coprecipitation, which were characterized thereafter. Optimal formulation proportions for SD were screened by in vitro dissolution assays, while its effects on improving absorption were investigated via in vivo pharmacokinetic assays. In addition, we evaluated the effects of MAG-HPMCAS SD on growth performance, antioxidant status, and gut microbiota in AA broilers. The powder samples prepared via antisolvent coprecipitation did not exhibit a crystal diffraction peak of MAG in powder X-ray diffractions or melting point peak in differential scanning calorimetry, proving the successful preparation of an amorphous solid dispersion system. The in vitro dissolution assay showed that the cumulative dissolution rate of MAG-HPMCAS(LF) SD (2:8, w/w) was 100%. Pharmacokinetic analyses revealed that the peak concentration (C-max) of MAG-HPMCAS SD was 5.07 +/- 0.73 mg/mL, which was 1.76 times greater than that of MAG. In addition, AUC(0-48) and t(1/2) of MAG-HPMCAS SD were 40.49 +/- 6.29 g center dot h/mL and 9.15 +/- 3.23 h, respectively, which were 2.17 and 2.56 times higher than those of MAG. Supplementation of MAG-HPMCAS SD in AA broilers significantly increased ADG (7-14 d and 15-21 d) and reduced feed conversion ratio (15-21 d) (P < 0.05). Bacterial diversity in the MAG-HPMCAS SD-supplemented group was greater than in the Control and MAG-supplemented group. Supplementation of MAG-HPMCAS SD stimulated the proliferation of beneficial bacteria, such as Lactobacillaceae and Bifidobacteriaceae. In conclusion, the MAG-HPMCAS SD prepared by coprecipitation improved the dissolution rate, the bioavailability of MAG, growth promotion, antioxidant effects and gut health in broilers.