Formulation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids.
CONTEXTS: Artemisinins and its derivatives are considered the basis in the treatment of Plasmodium falciparum malaria due to their high potency and rapid action. However, they have short half life, low solubility, and poor oral bioavailability, hence the need to formulate sustained release lipid particulate dosage form of these drugs.


OBJECTIVE
To formulate and evaluate artesunate-loaded solid lipid microparticles (SLMs) based on structured lipid matrices consisting of soybean oil and dika wax.


METHODS
The lipid matrices were characterized by differential scanning calorimetry (DSC), small-angle X-ray diffraction (SAXD), and wide-angle X-ray diffraction (WAXD). The SLMs were prepared by hot melt-homogenization. Time-dependent particle size analysis, time-dependent pH stability studies, encapsulation efficiency (EE%), and in vitro drug release were carried out on the SLMs. In vivo anti-malarial studies were performed using a modified Peter's 4-day suppressive protocol using Plasmodium berghei infected mice.


CONCLUSIONS
Thermograms of the lipid matrices showed modifications in the microstructure of dika wax as a result of inclusion of soybean oil. SAXD and WAXD diffractograms showed that the lipid matrices were found to be non-lamellar. Particle size of SLM increased with time, while the pH was almost constant. The SLMs had maximum EE% of 80.6% and sustained the release of artesunate more than the reference tablet. In vivo pharmacodynamic studies showed that the SLMs had significant (p < 0.05) reduction in parasitaemia compared with reference tablet.


CONCLUSIONS
Artesunate-loaded SLMs could be used once daily in the treatment of malaria.
Department of Pharmaceutics, University of Nigeria , Nsukka , Nigeria and.
E E
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Chinaeke
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Chime
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Onyishi
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Attama
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Okore
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry / Q000494:pharmacology*; D000077332:Artesunate; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects*; D053838:Scattering, Small Angle; D013024:Soybean Oil / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
D000962:Antimalarials; D037621:Artemisinins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010938:Plant Oils; C023475:dika fat; D000077332:Artesunate; D013024:Soybean Oil
Artesunate; Peter’s suppressive test; dika wax; hemozoin; parasitaemia reduction; soybean oil