Objective To prepare Glycyrrhiza polysaccharide-stabilized baicalin nanocrystals (Bai-NCs/GP) and investigate their physicochemical properties and in vivo pharmacokinetics. Methods Bai-NCs/GP were prepared using a media milling method. The formulation and process were optimized through single-factor experiments based on average particle size and polydispersity index (PDI). The optimized Bai-NCs/GP formulation was characterized for morphology, crystal form, solubility, and dissolution rate. LC-MS/MS was used to measure blood concentrations of Bai-NCs/GP and baicalin after oral administration in rats, comparing their bioavailability differences. Results The optimal formulation and processing parameters for Bai-NCs/GP were determined as follows: a baicalin to Glycyrrhiza polysaccharide ratio of 10:5, a baicalin content of 1.00%, a grinding speed of 1 400 r/min, and a grinding time of 24 h. Bai-NCs/GP exhibited irregular nanoparticles with an average particle size of (146.29 ± 8.07) nm, polydispersity index (PDI) of 0.22 ± 0.01, and ζ potential of (-21.60 ± 0.58) mV. Compared to baicalin, Bai-NCs/GP showed reduced crystallinity, 43- fold increased solubility, and significantly improved dissolution rate. The peak concentration (C_max) and AUC_0—t of Bai-NCs/GP were (2 318.65 ± 341.60) ng/mL and (34 439.68 ± 5 548.79) ng·h/mL, respectively, representing 2.31-fold and 2.77-fold increases over baicalin, with markedly enhanced oral bioavailability. Conclusion Glycyrrhiza polysaccharide can serve as a stabilizer in the preparation of baicalin nanocrystals. The resulting Bai-NCs/GP nanocrystals enhance the solubility and in vitro dissolution rate of baicalin, thereby improving its oral bioavailability.

baicalin  /  Glycyrrhiza polysaccharide  /  nanocrystals  /  media grinding  /  solubility  /  pharmacokinetics  /  dissolution  /  crystal form  /  bioavailability