Carboxymethyl starch as a solid dispersion carrier to enhance the dissolution and bioavailability of piperine and 18β-glycyrrhetinic acid

Abstract

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 C_max and AUC_0–24 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:

• Piperine
• 18β-glycyrrhetinic acid
• carboxymethyl starch
• solid dispersion
• pharmacokinetics
• bioavailability

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number 81803756]; The Six Talent Peak Projects in Jiangsu Province [grant number SWYY-010-2019]; Innovative practice plan for College students of Jiangsu province [grant number SJCX210690]; Hospital Pharmacy Foundation of Jiangsu Pharmaceutical Association [grant number A202006].