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AAPS PharmSciTech

, 20:108 | Cite as

Enhanced Solubility of Alkaloids by Complexation with Polycarboxylic Materials for Controlled Release Formulations: Case of Peschiera fuchsiaefolia

  • Kouadio Victorien Konan
  • Tien Canh Le
  • Mircea Alexandru MateescuEmail author
Research Article

Abstract

Malaria is a major public health problem with hundreds of thousands of deaths yearly. Extracts of Peschiera fuchsiaefolia (Pf), an Apocynaceae family plant, are used as malaria treatment by several populations. Artemisinin is another effective largely used antimalarial agent but susceptible to generate resistant forms of Plasmodium. To reduce the risk of new resistant strains’ appearance, the WHO recommended artemisinin-based combination therapy (ACT) with another bioactive agent, ensuring a long duration of antiplasmodial activity. Pf alkaloids are good candidates for ACT, but their solubility is very low. This research was aimed to improve the solubility of Pf alkaloids by complexation via their amine groups with carboxylate groups of carboxymethylstarch (CMS), an excipient used to formulate oral dosage forms for controlled drug release. It was found that when complexed as CMS-Pf, the solubility of Pf is increased (four to five times in function of dissolution medium). A new specific and faster approach to evaluate the solubility was proposed, measuring the effective saturation concentration of the compound of interest via one of its specific capacities, i.e., absorption capacity at a specific wavelength or antioxidant properties. This approach is more convenient for solubility evaluation of various active agents from complexes or crude extracts, or in heterogeneous samples. Also, the storage stability was markedly improved from 1 week for Pf co-processed with maltodextrin (MD/Pf) to several months for CMS-Pf (in similar controlled temperature and humidity conditions). The co-processing as MD/Pf or complexation as CMS-Pf affected physical properties but not the biological (i.e., antioxidant) activity of Pf.

KEY WORDS

alkaloid solubilization controlled release formulation natural soluble antioxidant agent Peschiera fuchsiaefolia solubility improvement solubility evaluation methods 

Notes

Acknowledgements

Support from NSERC (Natural Sciences and Engineering Research Council) of Canada granted to M.A.M. for this project is gratefully acknowledged.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

12249_2019_1315_MOESM1_ESM.docx (5.8 mb)
Supplementary Figures (DOCX 5888 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Kouadio Victorien Konan
    • 1
  • Tien Canh Le
    • 1
  • Mircea Alexandru Mateescu
    • 1
    Email author
  1. 1.Department of Chemistry, Research Chair on Enteric Dysfunctions “Allerdys”, Pharmaqam and CERMO-FC CentersUniversité du Québec à MontréalMontréalCanada

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