Centre of Excellence for Pharmaceutical Sciences (Pharmacen™), North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
AAPS PharmSciTech. 2024 Mar 22;25(4):67. doi: 10.1208/s12249-024-02783-0.
Despite being discovered over five decades ago, little is still known about ivermectin. Ivermectin has several physico-chemical properties that can result in it having poor bioavailability. In this study, polymorphic and co-crystal screening was used to see if such solid-state modifications can improve the oil solubility of ivermectin. Span® 60, a lipophilic non-ionic surfactant, was chosen as co-former. The rationale behind attempting to improve oil solubility was to use ivermectin in future topical and transdermal preparations to treat a range of skin conditions like scabies and head lice. Physical mixtures were also prepared in the same molar ratios as the co-crystal candidates, to serve as controls. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The FTIR spectra of the co-crystal candidates showed the presence of Span® 60's alkyl chain peaks, which were absent in the spectra of the physical mixtures. Due to the absence of single-crystal X-ray data, co-crystal formation could not be confirmed, and therefore these co-crystal candidates were referred to as co-processed crystalline solids. Following characterization, the solid-state forms, physical mixtures and ivermectin raw material were dissolved in natural penetration enhancers, i.e., avocado oil (AVO) and evening primrose oil (EPO). The co-processed solids showed increased oil solubility by up to 169% compared to ivermectin raw material. The results suggest that co-processing of ivermectin with Span® 60 can be used to increase its oil solubility and can be useful in the development of oil-based drug formulations.
伊维菌素虽然早在五十年前就被发现了，但人们对它的了解仍然很少。伊维菌素具有多种物理化学性质，这可能导致其生物利用度较差。在这项研究中，使用多晶型和共晶筛选来研究这种固体状态的修饰是否可以提高伊维菌素的油溶性。选择亲脂性非离子表面活性剂 Span® 60 作为共晶形成剂。试图提高油溶性的基本原理是在未来的局部和透皮制剂中使用伊维菌素来治疗各种皮肤疾病，如疥疮和头虱。还以相同的摩尔比制备了物理混合物作为对照。使用 X 射线粉末衍射（XRPD）、傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）和热重分析（TGA）进行固态特性分析。共晶候选物的 FTIR 光谱显示出 Span® 60 的烷基链峰的存在，而物理混合物的光谱中则没有这些峰。由于缺乏单晶 X 射线数据，无法确认共晶的形成，因此这些共晶候选物被称为共处理结晶固体。经过特性分析，将固态形式、物理混合物和伊维菌素原料溶解在天然渗透增强剂中，即鳄梨油（AVO）和月见草油（EPO）中。与伊维菌素原料相比，共处理固体的油溶性提高了高达 169%。结果表明，用 Span® 60 共处理伊维菌素可以提高其油溶性，这对开发油基药物制剂可能有用。
