Author(s):
Shijith KV, Narayana Charyulu R., Sarath Chandran C, Prakash Patil, Jobin Jose
Email(s):
narayana@nitte.edu.in
DOI:
10.52711/0974-360X.2025.00400
Address:
Shijith KV1,2, Narayana Charyulu R.2*, Sarath Chandran C1, Prakash Patil3 , Jobin Jose2
1College of Pharmaceutical Sciences, Government Medical College, Kannur, Kerala, India.
2NGSM Institute of Pharmaceutical Sciences, (NITTE Deemed to be University), Mangalore, Karnataka, India.
3Central Research Lab, KS Hegde Medical Academy, (NITTE Deemed to be University), Mangalore, Karnataka, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 6,
Year - 2025
ABSTRACT:
Gastro Plus, an in silico simulation software, predicts drug absorption behavior in humans and animals using an advanced compartmental absorption and transit model. This study explored the application of GastroPlus and ADMET Predictors to predict the pharmacokinetic behavior of mangiferin (MGF), a naturally occurring active pharmaceutical ingredient with diverse biological properties. The pharmaceutical applications of mangiferin are limited owing to its poor bioavailability. By utilizing GastroPlus along with the ADMET Predictor module, researchers have gained valuable insights into the behavior of MGF, assisting in the development of optimized formulations. A simulation using GastroPlus predicted the oral absorption and plasma concentration profile of MGF, showing poor bioavailability owing to first-pass metabolism and low absorption. Regional absorption indicated that the first part of the intestine may be the predominant site of MGF absorption. Calibration of the compartmental model with the in vivo and in vitro data validated the simulation results. Parameter sensitivity analysis identified solubility, permeability, and initial dose as the critical factors influencing the oral absorption of MGF. This study highlighted the significance of effective permeability (Peff) in enhancing MGF's bioavailability of MGF. Optimization of these factors may lead to the development of effective and bioavailable formulations of MGF. The combination of GastroPlus and ADMET Predictor may provide valuable insights into the pharmacokinetic behavior of MGF.
Cite this article:
Shijith KV, Narayana Charyulu R., Sarath Chandran C, Prakash Patil, Jobin Jose. Predicting the Pharmacokinetic behavior of Mangiferin using Gastro Plus and ADMET Predictor: Insights for Optimized Formulation Development. Research Journal of Pharmacy and Technology. 2025;18(6):2796-2. doi: 10.52711/0974-360X.2025.00400
Cite(Electronic):
Shijith KV, Narayana Charyulu R., Sarath Chandran C, Prakash Patil, Jobin Jose. Predicting the Pharmacokinetic behavior of Mangiferin using Gastro Plus and ADMET Predictor: Insights for Optimized Formulation Development. Research Journal of Pharmacy and Technology. 2025;18(6):2796-2. doi: 10.52711/0974-360X.2025.00400 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-6-53
REFERENCE:
1. Debnath S. Kumar T. H. H. An Overview on Pharmacokinetics and Pharmacokinetic Modeling. Asian J. Res. Pharm. Sci. 2020; 10, 124.
2. Hu Y. Smith D. E. In Silico Prediction of the Absorption and Disposition of Cefadroxil in Humans using an Intestinal Permeability Method Scaled from Humanized PepT1 Mice. Drug Metab. Dispos. 2019; 47, 173–183.
3. Arivukkarasu R. Rajasekaran, A. Hussain S. H. B. Ajnas M. Simultaneous detection of Rutin, Quercetin, Gallic acid, Caffeic acid, Ferulic acid, Coumarin, Mangiferin and Catechin in Hepatoprotective commercial herbal formulations by HPTLC technique. Res. J. Pharmacogn. Phytochem. 2018; 10: 59.
4. Abriyani E. Fikayuniar L. Screening phytochemical, antioxidant activity and vitamin c assay from bungo perak-perak (Begonia versicolar irmsch) leaves. Asian J. Pharm. Res. 2020; 10: 183.
5. Singh A. A Review of various aspects of the Ethnopharmacological, Phytochemical, Pharmacognostical, and Clinical significance of selected Medicinal plants. Asian J. Pharm. Technol. 2022; 349–360 doi:10.52711/2231-5713.2022.00055.
6. Baseer Khan AJ B. Arif M. Microwave Supported Extraction and Optimization of Flavonoid Mangiferin from Mangifera indica L. Stem Bark using Orthogonal Array Design. Res. J. Pharm. Technol. 2023; 1113–1117 doi:10.52711/0974-360X.2023.00185.
7. B Mathew J. Fathima Z. Raviraj C. Mathew A. Quantitative Estimation of Mangiferin and Molecular Docking Simulation of Salacia reticulata Formulation. Res. J. Pharm. Technol. 2024; 578–584 doi:10.52711/0974-360X.2024.00090.
8. Indalkar YR. Pimpodkar NV. Godase AS. Gaikwad PS. A Compressive Review on the Study of Nanotechnology for Herbal Drugs. Asian J. Pharm. Res. 2015; 5: 203.
9. Nistane NT. Herbal Nanoparticles against Cancer. Res. J. Pharm. Dos. Forms Technol. 2019; 11: 247.
10. Ahmad W.Khan T. Basit, I. Imran JA Comprehensive Review on Targeted Drug Delivery System. Asian J. Pharm. Res.2022; 335–340 doi:10.52711/2231-5691.2022.00053.
11. Samajdar S. In silico ADME prediction of Phytochemicals present in Piper longum. Asian J. Res. Pharm. Sci.2023; 89–93 doi:10.52711/2231-5659.2023.00017.
12. Grbic S. Parojcic J. Djuric Z. Computer-aided biopharmaceutical characterization: gastrointestinal absorption simulation. in Computer-Aided Applications in Pharmaceutical Technology. Elsevier. 2013; 177–232. doi:10.1533/9781908818324.177.
13. Habeeb, M. et al. Development Characterization and Molecular Simulation studiesof Metoclopramide HCl and Tramadol HCl Bilayer Tablets. Res. J. Pharm. Technol. 2022; 529–534. doi:10.52711/0974-360X.2022.00085.
14. Hosea NA.Jones HM. Predicting Pharmacokinetic Profiles Using in Silico Derived Parameters. Mol. Pharm. 2013; 10: 1207–1215.
15. M Mukadam. MM Jagdale D. In silico ADME/T Prediction of Steroidal Chalcone derivatives using Swiss ADME and OSIRIS explorer. Res. J. Pharm. Technol. 2024; 843–848 doi:10.52711/0974-360X.2024.00130.
16. Sohlenius-Sternbeck AK. Terelius Y. Evaluation of ADMET Predictor in Early Discovery Drug Metabolism and Pharmacokinetics Project Work. Drug Metab. Dispos. 2022; 50, 95–104.
17. Nitin D. Love Kumar S. Prediction of In-silico ADMET Properties and Molecular docking study of Substituted Thiadiazole for screening of Antiviral activity against protein target Covid-19 main protease. Res. J. Pharm. Technol. 2023; 5802–5807. doi:10.52711/0974-360X.2023.00939.
18. PubChem. Mangiferin. https://pubchem.ncbi.nlm.nih.gov/compound/5281647.
19. Morozkina SN. Nhung Vu TH. Generalova YE. Snetkov PP. Uspenskaya MV. Mangiferin as New Potential Anti-Cancer Agent and Mangiferin-Integrated Polymer Systems—A Novel Research Direction. Biomolecules 2021; 11, 79.
20. Duque MD. et al. In Silico Prediction of Plasma Concentrations of Fluconazole Capsules with Different Dissolution Profiles and Bioequivalence Study Using Population Simulation. Pharmaceutics. 2019; 11: 215.
21. Suharti N. et al. In Silico Prediction and In Vitro Cytotoxic Activity of Arbuscular Mycorrhizal Fungi Induced Zingiber officinale Var. Rubrum. Res. J. Pharm. Technol. 2022; 4913–4918, doi:10.52711/0974-360X.2022.00825.
22. Vardhan H. Mittal P. Adena SKR.Upadhyay M. Mishra B. Development of long-circulating docetaxel loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles: Optimization, pharmacokinetic, cytotoxicity and in vivo assessments. Int. J. Biol. Macromol. 2017; 103: 791–801.
23. Sjögren E. Thörn H. Tannergren C. In Silico Modeling of Gastrointestinal Drug Absorption: Predictive Performance of Three Physiologically Based Absorption Models. Mol. Pharm. 2016; 13: 1763–1778.
24. Sjögren, E. et al. In silico predictions of gastrointestinal drug absorption in pharmaceutical product development: Application of the mechanistic absorption model GI-Sim. Eur. J. Pharm. Sci. 2013; 49: 679–698.
25. Grbic S. Lukic V. Kovacevic I. Parojcic J. Djuric Z. An investigation into the possibilities and limitations of in silico absorption modeling: GastroPlusTM simulation of nimesulide oral absorption. in Proceedings of The 2nd Electronic Conference on Pharmaceutical Sciences 816 (MDPI, Sciforum.net, 2012). doi:10.3390/ecps2012-00816.
26. Grbic S. Lukic V. Kovacevic I. Parojcic J. Djuric Z. An investigation into the possibilities and limitations of in silico absorption modeling: GastroPlusTM simulation of nimesulide oral absorption. in Proceedings of The 2nd Electronic Conference on Pharmaceutical Sciences 816 (MDPI, Sciforum.net, 2012). doi:10.3390/ecps2012-00816.
27. Kovacevic I. Parojčić J. Homšek I. Tubić-Grozdanis M. Langguth P. Justification of Biowaiver for Carbamazepine, a Low Soluble High Permeable Compound, in Solid Dosage Forms Based on IVIVC and Gastrointestinal Simulation. Mol. Pharm. 2009; 6: 40–47.
28. Peter JS. et al. In Silico approach to predict the potential binding affinity of the active Ingredient of the Macrotyloma uniflorum seed against orphan nuclear receptor. Res. J. Pharm. Technol. 2021; 14: 694–700.
29. Prado Y. et al. Acute and 28-day subchronic toxicity studies of mangiferin, a glucosyl xanthone isolated from Mangifera indica L. stem bark. 11.
30. Ma H. Chen H. Sun L. Tong L. Zhang T. Improving permeability and oral absorption of mangiferin by phospholipid complexation. Fitoterapia 2014; 93: 54–61.
31. Kammalla AK. et al. Comparative Pharmacokinetic Study of Mangiferin After Oral Administration of Pure Mangiferin and US Patented Polyherbal Formulation to Rats. AAPS PharmSciTech 2015; 16: 250–258.
32. Khurana RK. et al. Exploring and validating physicochemical properties of mangiferin through GastroPlus® software. Future Sci. 2017; OA 3: FSO167.