Agubata Chukwuma O, Nzekwe Ifeanyi T, Attama Anthony A, Mueller-Goymann Christel C, Onunkwo Godswill C
Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka, Enugu State, Nigeria.
Department of Pharmaceutics and Pharmaceutical Technology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
Int J Pharm. 2015 Jan 15;478(1):202-222. doi: 10.1016/j.ijpharm.2014.11.044. Epub 2014 Nov 20.
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.
蒿甲醚的抗疟活性取决于其生物利用度。本研究的目的是使用基于同型脂质的微粒来提高亲脂性蒿甲醚的溶解度、生物利用度和治疗效果。从加蓬油桃木（Irvingia gabonensis var. excelsa，即Irvingia wombolu）中提取了牛油树脂，并通过差示扫描量热法（DSC）和广角X射线衍射（WAXD）对其与磷脂（®）90G（P90G）形成的脂质基质（LM）进行了表征。制备了固体脂质微粒，进行了表征，分别填充并压制成胶囊和片剂，并研究了药物释放情况。在小鼠中评估了蒿甲醚固体脂质微粒的体内抗疟活性。在P90G存在的情况下，植物脂质的结晶度降低，P90G整合到了牛油树脂晶格中。含有3:1牛油树脂/P90G组成的固体脂质微粒分散体通过透析膜显示出更高的扩散和渗透性，而较低比例的P90G（9:1脂质基质）有利于提高蒿甲醚从胶囊中的溶出速率（p<0.05）。与对照组相比，给予固体脂质微粒分散体的小鼠疟原虫生长抑制百分比显著增加（p<0.05），寄生虫血症降低。因此，用同型脂质和P90G的复合混合物制备的固体脂质微粒可用于提高蒿甲醚的溶解度、溶出度、渗透性、生物利用度和抗疟效果。
