title: Formulation, characterization and anti-malarial activity of homolipid-based artemether microparticles.
abstract: The anti-malarial activity of artemether is dependent on its bioavailability. The purpose of the research is to improve the solubility, bioavailability and therapeutic efficacy of lipophilic artemether using homolipid-based microparticles. Irvingia fat was extracted from Irvingia gabonensis var. excelsa (Irvingia wombolu), and its lipid matrices (LM) with Phospholipon(®) 90G (P90G) were characterized by differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). Solid lipid microparticles were formulated, characterized, filled and compressed into capsules and tablets, respectively, and drug release studied. In vivo anti-plasmodial activity of artemether SLMs was evaluated in mice. The crystallinity of the phyto-lipid reduced in the presence of P90G, which was integrated into the irvingia fat crystal lattice. SLM dispersions with 3:1 irvingia fat/P90G composition showed higher diffusion and permeability through dialysis membrane while lower proportion of P90G (9:1 LM) favored increased dissolution rate of artemether from capsules (p<0.05). Significant increase (p<0.05) in % plasmodial growth inhibition and reduced parasitemia were observed in mice administered with the SLM dispersions compared with the controls. Therefore, SLMs prepared with composite mixtures of a homolipid and P90G could be used to improve the solubility, dissolution, permeability, bioavailability and anti-malarial efficacy of artemether.
authors.affiliation: Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka, Enugu State, Nigeria. Electronic address: chukwuma.agubata@unn.edu.ng.
authors.forename: Chukwuma O
authors.initials: CO
authors.lastname: Agubata
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
authors.forename: Ifeanyi T
authors.initials: IT
authors.lastname: Nzekwe
authors.affiliation: Department of Pharmaceutics, University of Nigeria, Nsukka, Enugu State, Nigeria.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Attama
authors.affiliation: Institut für Pharmazeutische Technologie, Technische Universität Carolo-Wilhelmina zu Braunschweig, Braunschweig, Germany.
authors.forename: Christel C
authors.initials: CC
authors.lastname: Mueller-Goymann
authors.affiliation: Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka, Enugu State, Nigeria.
authors.forename: Godswill C
authors.initials: GC
authors.lastname: Onunkwo
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D002482:Cellulose; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D005223:Fats / Q000737:chemistry; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010962:Plasmodium berghei / Q000187:drug effects; D012639:Seeds; D012995:Solubility
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D005223:Fats; D010713:Phosphatidylcholines; C051375:dikanut; C585968:phospholipon 90G; D002482:Cellulose; D000077549:Artemether
keywords: Anti-malarial activity; Artemether (PubChem CID: 456408); Croscarmellose sodium (PubChem CID: 6328154); Homolipid; Microcrystalline cellulose (PubChem CID: 14055602); Microparticles; Starch from maize (PubChem CID: 439341)