Weerapol Yotsanan, Limmatvapirat Sontaya, Nunthanid Jurairat, Sriamornsak Pornsak
Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand.
AAPS PharmSciTech. 2014 Apr;15(2):456-64. doi: 10.1208/s12249-014-0078-y. Epub 2014 Jan 23.
A simple but novel mixed surfactant system was designed to fabricate a self-nanoemulsifying drug delivery system (SNEDDS) based on hydrophilic-lipophilic balance (HLB) value. The impacts of HLB and molecular structure of surfactants on the formation of SNEDDS were investigated. After screening various oils and surfactants, nifedipine (NDP)-loaded liquid SNEDDS was formulated with Imwitor(®) 742 as oil and Tween(®)/Span(®) or Cremophor(®)/Span(®) as mixed surfactant. Droplet size of the emulsions obtained after dispersing SNEDDS containing Tween(®)/Span(®) in aqueous medium was independent of the HLB of a mixed surfactant. The use of the Cremophor(®)/Span(®) blend gave nanosized emulsion at higher HLB. The structure of the surfactant was found to influence the emulsion droplet size. Solid SNEDDS was then prepared by adsorbing NDP-loaded liquid SNEDDS comprising Cremophor(®) RH40/Span(®) 80 onto Aerosil(®) 200 or Aerosil(®) R972 as inert solid carrier. Solid SNEDDS formulations using higher amounts (30-50% w/w) of Aerosil(®) 200 exhibited good flow properties with smooth surface and preserved the self-emulsifying properties of liquid SNEDDS. Differential scanning calorimetry and X-ray diffraction studies of solid SNEDDS revealed the transformation of the crystalline structure of NDP due to its molecular dispersion state. In vitro dissolution study demonstrated higher dissolution of NDP from solid SNEDDS compared with NDP powder.
基于亲水亲油平衡（HLB）值，设计了一种简单但新颖的混合表面活性剂体系来制备自纳米乳化药物递送系统（SNEDDS）。研究了HLB和表面活性剂分子结构对SNEDDS形成的影响。在筛选了各种油和表面活性剂后，以Imwitor(®) 742为油相，吐温(®)/司盘(®)或聚氧乙烯蓖麻油(®)/司盘(®)为混合表面活性剂，制备了载硝苯地平（NDP）的液体SNEDDS。将含吐温(®)/司盘(®)的SNEDDS分散在水介质中得到的乳液滴大小与混合表面活性剂的HLB无关。使用聚氧乙烯蓖麻油(®)/司盘(®)混合物在较高HLB时可得到纳米级乳液。发现表面活性剂的结构会影响乳液滴大小。然后通过将包含聚氧乙烯蓖麻油(®) RH40/司盘(®) 80的载NDP液体SNEDDS吸附到作为惰性固体载体的气相二氧化硅(®) 200或气相二氧化硅(®) R972上，制备了固体SNEDDS。使用较高含量（30 - 50% w/w）气相二氧化硅(®) 200的固体SNEDDS制剂表现出良好的流动性，表面光滑，并保留了液体SNEDDS的自乳化性能。固体SNEDDS的差示扫描量热法和X射线衍射研究表明，由于NDP的分子分散状态，其晶体结构发生了转变。体外溶出研究表明，与NDP粉末相比，固体SNEDDS中NDP的溶出度更高。
