Objective: To investigate the applicability of carboxymethyl starch (CMS) as a carrier to prepare solid dispersions (SDs) of piperine (PIP) and 18β-glycyrrhetinic acid (β-GA) (PIP-CMS and β-GA-CMS SDs) and to explore the influence of drug properties on carrier selection.
Significance: The low oral bioavailability of natural therapeutic molecules, including PIP and β-GA, severely restricts their pharmaceutical applications. Moreover, CMS, a natural polymer, is rarely reported as a carrier for SDs.
Methods: PIP-CMS and β-GA-CMS SDs were prepared using the solvent evaporation method. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) were used for formulation characterization. Additionally, drug release characteristics were investigated.
Results: In vitro dissolution studies showed that the dissolutions of PIP-CMS and β-GA-CMS SDs were 1.90-2.04 and 1.97-2.22 times higher than pure PIP and β-GA, respectively, at a drug:polymer ratio of 1:6. DSC, XRPD, FT-IR, and SEM analyses confirmed the formation of SDs in their amorphous states. Significant improvements in Cmax and AUC0-24 h of PIP-CMS and β-GA-CMS SDs (17.51 ± 8.15 μg/mL and 210.28 ± 117.13 μg·h/mL, respectively) and (32.17 ± 9.45 μg/mL and 165.36 ± 38.75 μg·h/mL, respectively) were observed in the pharmacokinetic study. Compared with weakly acidic β-GA, loading weakly basic PIP seemed to have a profound effect on stability through intermolecular forces.
Conclusions: Our findings showed CMS could be a promising carrier for SDs, and loading weakly basic drug may be more suitable, especially in binary SDs system.
Keywords: 18β-glycyrrhetinic acid; Piperine; bioavailability; carboxymethyl starch; pharmacokinetics; solid dispersion.