Department of Chemical, Biochemical, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, New Jersey, USA.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, 68198-5880, USA.
AAPS PharmSciTech. 2018 Aug;19(6):2572-2584. doi: 10.1208/s12249-018-1089-x. Epub 2018 Jun 14.
This proof-of-concept study explores the feasibility of using a drug-loaded hydrophilic polymeric layer sandwiched between two hydrophobic layers for improving film drug load while achieving sustained release of poorly water-soluble drug. Such films having total thickness in range ~ 146-250 μm were prepared by slurry-based casting using hydrophilic hydroxypropyl methylcellulose (HPMC) as matrix layer containing fenofibrate (FNB) as the model drug, encased between two very thin rate-limiting layers of 10 μm each of hydrophobic poly-ɛ-caprolactone (PCL). Film precursor slurry consisted of HPMC with plasticizer and water along with micronized FNB powders, which were dry-coated with hydrophilic silica. Characterization techniques demonstrated the presence of homogeneously dispersed crystalline FNB in films. The films are very thin and hence two-dimensional; hence, average drug load per unit area in range ~ 5 to ~ 9 mg/cm could be achieved by altering the thickness of the drug matrix layer. Drug amount and drug content uniformity were measured through assay of ten circular samples ~ 0.712 cm in area punched out using a circular-shaped punch tool. Drug release rate was investigated using USP IV flow-through cell and surface dissolution imaging system. Thinner films followed Fickian diffusion, and thicker films followed non-Fickian anomalous diffusion. Overall, the application of middle layer thickness could be used as a tool to manipulate drug load without the need for altering its formulation or precursor preparation by changing its thickness, hence achieving relatively high drug loading yet having sustained release of drug.
这项概念验证研究探索了在两层疏水性层之间夹一层载药亲水性聚合物层来提高薄膜药物负载量并实现难溶性药物持续释放的可行性。采用基于浆料的铸造法制备了总厚度在 146-250 μm 范围内的此类薄膜，以亲水性羟丙基甲基纤维素（HPMC）为基质层，其中包含作为模型药物的非诺贝特（FNB），并夹在两层非常薄的各 10 μm 厚疏水性聚己内酯（PCL）限速层之间。薄膜前驱体浆料由 HPMC、增塑剂和水以及微米化的 FNB 粉末组成，HPMC 粉末用亲水性二氧化硅干涂。表征技术表明，薄膜中存在均匀分散的结晶 FNB。这些薄膜非常薄，属于二维结构；因此，可以通过改变药物基质层的厚度来实现 5-9 mg/cm2 范围内的单位面积药物负载量。通过使用圆形打孔工具冲出 10 个面积约 0.712 cm2 的圆形样品来测量药物量和药物含量均匀性。通过 USP IV 流动池和表面溶解成像系统研究了药物释放速率。较薄的薄膜遵循菲克扩散，而较厚的薄膜遵循非菲克异常扩散。总的来说，中间层厚度的应用可以作为一种工具来操纵药物负载量，而无需通过改变其厚度来改变其制剂或前体制备，从而实现相对较高的药物负载量和药物的持续释放。
