Antiplasmodial Combined Formulation of Artemisinin with Peschiera fuchsiaefolia Bis-Indole Alkaloids

Abstract

Antimalarial agents used as monotherapy are increasingly ineffective due to the emergence of Plasmodium resistant strains. Artemisinin (Arte), extracted from Artemisia annua, presents a good efficiency against the Plasmodium strains and is currently used to treat malaria. To avoid the appearance of new resistant strains to artemisinin, the use of Artemisinin-based Combination Therapy (ACT) with another antimalaria agent was recommended by WHO to provide an effective cure and delayed resistance. Although combined formulations of various drugs with Artemisinin have been developed, their release is immediate, and they require multiple doses with side detrimental effects and effectiveness still desired. To improve its efficiency, controlled release formulations were developed to ensure long-term antiplasmodial activity by associating Artemisinin with a natural antimalarial agent extracted from Peschiera fuchsiaefolia (Pf). The Pf extract (containing mostly low soluble alkaloids) was complexed with carboxymethylcellulose to improve its solubility and stability. Two formulation types are reported. As bilayer tablet dosage form, the kinetic release pattern was an immediate release of Artemisinin, followed by a slow sustained release of Pf for 12 h. As monolithic tablet, the release profile shows a simultaneous sustained release of the two active agents, about of 10 h for Arte and 12 h for Pf.

Keywords: Antioxidant; Complexation; Controlled release; Drug-combination particles; Formulation; Natural products; Oral drug delivery; Poorly water-soluble drug; Pre-formulation; Solubility.