Enhancing oral bioavailability of andrographolide using solubilizing agents and bioenhancer: comparative pharmacokinetics of Andrographis paniculata formulations in beagle dogs

Abstract

Context

The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility.

Objective

This work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in Andrographis paniculata (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer.

Materials and methods

Four groups of beagles were compared: (1) A. paniculata powder alone (control), (2) A. paniculata powder with 50% weight/weight (w/w) β-cyclodextrin solubilizer, (3) A. paniculata powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) A. paniculata powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. All groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days.

Results

Thirteen chemical compounds were identified in A. paniculata powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. A. paniculata co-administration with either 50% w/w β-cyclodextrin or 1% w/w SDS, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces.

Conclusion

The combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for A. paniculata formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted.

Keywords:

• Sodium dodecyl sulfate
• β-cyclodextrin
• piperine
• green chiretta

Acknowledgements

The authors would like to thank Miss Jittra Saehun for her contribution to the sample preparation in this study, and Dr. James M. Dubbs for proofreading. Lastly, we express our appreciation to the Food and Drug Quality Unit at Chulabhorn Research Institute for conducting the quantitative analysis of A. paniculata capsules.

Author contributions

PK initiated the conception. PS, TB, TK, and PK developed the design. PS, TB, NN, TJ, TK, KS, and PK conducted the experiments. PS, TB, NN, and TJ analyzed the results. PS, TB, and TJ prepared the first draft of the manuscript. PS, TB, NN, TJ, TK, KS, and PK reviewed and edited the manuscript.

Disclosure statement

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

Data availability statement

The datasets generated and/or analyzed during the present study are not publicly available but are available from the corresponding author on reasonable request that needs a consensus from colleagues.

Additional information

Funding

This work was supported by the Mahidol University under Grant to Phisit Khemawoot; and the Administration and Capital Management Unit for Enhancing the Competitiveness of the Country under Grant PMUC No. C17F640237 to Phisit Khemawoot.