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

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

AAPS PharmSciTech

Department of Chemistry, Research Chair on Enteric Dysfunctions "Allerdys", Pharmaqam and CERMO-FC Centers, Université du Québec à Montréal, C.P. 8888, Branch A, Montréal, Québec, H3C 3P8, Canada.

Published: February 2019

AI Article Synopsis

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.

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Source
http://dx.doi.org/10.1208/s12249-019-1315-1DOI Listing

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