KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, 3000 Leuven, Belgium.
Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent, Belgium.
Eur J Pharm Biopharm. 2019 Nov;144:79-90. doi: 10.1016/j.ejpb.2019.09.005. Epub 2019 Sep 6.
Despite the fact that solid dispersions are gaining momentum, the number of polymers that have been used as a carrier during the past 50 years is rather limited. Recently, the poly(2-alkyl-2-oxazoline) (PAOx) polymer class profiled itself as a versatile platform for a wide variety of applications in drug delivery, including their use as amorphous solid dispersion (ASD) carrier. The aim of this study was to investigate the potential of poly(2-ethyl-2-oxazoline) (PEtOx) by applying a benchmark approach with well-known, commercially available carriers (i.e. polyvinylpyrrolidone (PVP) K30, poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) 64 and hydroxypropylmethylcellulose (HPMC)). For this purpose, itraconazole (ITC) and fenofibrate (FFB) were selected as poorly water-soluble model drugs. The four polymers were compared by establishing their supersaturation maintaining potential and by investigating their capability as carrier for ASDs with high drug loadings. Spray drying, as well as hot melt extrusion and cryo-milling were implemented as ASD manufacturing technologies for comparative evaluation. For each manufacturing technique, the formulations with the highest possible drug loadings were tested with respect to in vitro drug release kinetics. This study indicates that PEtOx is able to maintain supersaturation of the drugs to a similar extent as the commercially available polymers and that ASDs with comparable drug loadings can be manufactured. The results of the in vitro dissolution tests reveal that high drug release can be obtained for PEtOx formulations. Overall, proof-of-concept is provided for the potential of PEtOx for drug formulation purposes.
尽管固体分散体越来越受到关注，但在过去 50 年中，用作载体的聚合物数量相当有限。最近，聚（2-烷基-2-恶唑啉）（PAOx）聚合物因其在药物传递中的各种应用而成为多功能平台，包括将其用作无定形固体分散体（ASD）载体。本研究旨在通过采用基准方法，使用已知的商业可用载体（即聚乙烯吡咯烷酮（PVP）K30、聚（聚乙烯吡咯烷酮-醋酸乙烯酯）（PVP-VA）64 和羟丙基甲基纤维素（HPMC）），研究聚（2-乙基-2-恶唑啉）（PEtOx）的潜力。为此，选择伊曲康唑（ITC）和非诺贝特（FFB）作为水溶性差的模型药物。通过建立过饱和度维持能力并研究其作为高载药量 ASD 载体的能力，对四种聚合物进行了比较。喷雾干燥、热熔挤出和冷冻研磨被用作 ASD 制造技术进行比较评估。对于每种制造技术，都对具有尽可能高药物载药量的配方进行了体外药物释放动力学测试。本研究表明，PEtOx 能够以与市售聚合物相似的程度维持药物的过饱和度，并且可以制造具有类似药物载药量的 ASD。体外溶解试验的结果表明，PEtOx 配方可以获得高药物释放。总体而言，为 PEtOx 用于药物制剂目的的潜力提供了概念验证。
