Djekic Ljiljana, Jankovic Jovana, Čalija Bojan, Primorac Marija
University of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Pharmacy Jankovic, Miloša Bajića 13, 21000 Novi Sad, Serbia.
Int J Pharm. 2017 Aug 7;528(1-2):372-380. doi: 10.1016/j.ijpharm.2017.06.028. Epub 2017 Jun 12.
The study aimed to develop semisolid self-microemulsifying drug delivery systems (SMEDDSs) as carriers for oral delivery of aciclovir in hard hydroxypropylmethyl cellulose (HPMC) capsules. Six self-dispersing systems (SD1-SD6) were prepared by loading aciclovir into the semisolid formulations consisting of medium chain length triglycerides (lipid), macrogolglycerol hydroxystearate (surfactant), polyglyceryl-3-dioleate (cosurfactant), glycerol (hydrophilic cosolvent), and macrogol 8000 (viscosity modifier). Their characterization was performed in order to identify the semisolid system with rheological behaviour suitable for filling in hard HPMC capsules and fast dispersibility in acidic and alkaline aqueous media with formation of oil-in-water microemulsions. The optimal SMEDDS was loaded with aciclovir at two levels (2% and 33.33%) and morphology and aqueous dispersibility of the obtained systems were examined by applying light microscopy and photon correlation spectroscopy (PCS), respectively. The assessment of diffusivity of aciclovir from the SMEDDSs by using an enhancer cell model, showed that it was increased at a higher drug loading. Differential scanning calorimetry (DSC) analysis indicated that the SMEDDSs were semisolids at temperatures up to 50°C and physically stable and compatible with HPMC capsules for 3 months storage at 25°C and 4°C. The results of in vitro release study revealed that the designed solid dosage form based on the semisolid SMEDDS loaded with the therapeutic dose of 200mg, may control partitioning of the solubilized drug from in situ formed oil-in-water microemulsion carrier into the sorrounding aqueous media, and hence decrease the risk for precipitation of the drug.
本研究旨在开发半固体自微乳化药物递送系统（SMEDDS），作为阿昔洛韦口服给药的载体，用于硬羟丙基甲基纤维素（HPMC）胶囊。通过将阿昔洛韦负载到由中链甘油三酯（脂质）、聚乙二醇氢化硬脂酸甘油酯（表面活性剂）、聚甘油-3-二油酸酯（助表面活性剂）、甘油（亲水性助溶剂）和聚乙二醇8000（粘度调节剂）组成的半固体制剂中，制备了六种自分散系统（SD1-SD6）。对其进行表征，以确定具有适合填充硬HPMC胶囊的流变行为以及在酸性和碱性水性介质中快速分散形成水包油微乳液的半固体系统。将最佳SMEDDS以两种水平（2%和33.33%）负载阿昔洛韦，并分别通过光学显微镜和光子相关光谱法（PCS）检查所得系统的形态和水性分散性。使用增强细胞模型评估阿昔洛韦从SMEDDS中的扩散率，结果表明在较高药物负载量下扩散率增加。差示扫描量热法（DSC）分析表明，SMEDDS在高达50°C的温度下为半固体，在25°C和4°C下储存3个月时物理稳定且与HPMC胶囊相容。体外释放研究结果表明，基于负载200mg治疗剂量的半固体SMEDDS设计的固体剂型，可以控制溶解药物从原位形成的水包油微乳液载体向周围水性介质中的分配，从而降低药物沉淀的风险。
