Schmied Fabian-Pascal, Bernhardt Alexander, Klein Sandra
Institute of Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, University of Greifswald, Felix-Hausdorff-Straße 3, 17489 Greifswald, Germany.
Research, Development & Innovation, Evonik Operations GmbH, Kirschenallee, 64293 Darmstadt, Germany.
Pharmaceuticals (Basel). 2022 Sep 11;15(9):1135. doi: 10.3390/ph15091135.
The present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and different polymeric carriers. Experiments were performed with L-SNEDDS formulations containing celecoxib, efavirenz or fenofibrate as model drugs. A major objective was to identify a polymeric carrier and process parameters that would enable the preparation of stable S-SNEDDS without impairing the release behavior and storage stability of the L-SNEDDS used and, if possible, even improving them further. In addition to commercially available (co)polymers already used in the field of HME, a particular focus was on the evaluation of different variants of a recently developed aminomethacrylate-based copolymer (ModE) that differed in M. Immediately after preparation, the L-SNEDDS and S-SNEDDS formulations were tested for amorphicity by differential scanning calorimetry. Furthermore, solubility and dissolution tests were performed. In addition, the storage stability was investigated at 30 °C/65% RH over a period of three and six months, respectively. In all cases, amorphous formulations were obtained and, especially for the model drug celecoxib, S-SNEDDS were developed that maintained the rapid and complete drug release of the underlying L-SNEDDS even over an extended storage period. Overall, the data obtained in this study suggest that the presented S-SNEDDS approach is very promising, provided that drug-loaded L-SNEDDS are co-processed with a suitable polymeric carrier. In the case of celecoxib, the E-173 variant of the novel ModE copolymer proved to be a novel polymeric carrier with great potential for application in S-SNEDDS. The presented approach will, therefore, be pursued in future studies to establish S-SNEDDS as an alternative formulation to other amorphous systems.
本研究聚焦于一种新的制剂方法，以提高水溶解度差的药物的溶解度。采用热熔挤出（HME）工艺，通过将液体自纳米乳化药物递送系统（L-SNEDDS）与不同的聚合物载体共挤出，制备载药固体自纳米乳化药物递送系统（S-SNEDDS）。以含塞来昔布、依法韦仑或非诺贝特的L-SNEDDS制剂作为模型药物进行实验。一个主要目标是确定一种聚合物载体和工艺参数，能够制备出稳定的S-SNEDDS，同时不损害所用L-SNEDDS的释放行为和储存稳定性，并且如果可能的话，进一步改善它们。除了HME领域已使用的市售（共）聚合物外，特别关注对最近开发的一种基于氨基甲基丙烯酸酯的共聚物（ModE）的不同变体进行评估，这些变体在分子量方面存在差异。制备后立即通过差示扫描量热法对L-SNEDDS和S-SNEDDS制剂进行无定形测试。此外，进行了溶解度和溶出度测试。另外，分别在30℃/65%相对湿度下研究了三个月和六个月的储存稳定性。在所有情况下，均获得了无定形制剂，尤其是对于模型药物塞来昔布，所开发的S-SNEDDS即使在延长的储存期内也能保持基础L-SNEDDS的快速和完全药物释放。总体而言，本研究获得的数据表明，只要将载药L-SNEDDS与合适的聚合物载体共同加工，所提出的S-SNEDDS方法非常有前景。对于塞来昔布，新型ModE共聚物的E-173变体被证明是一种在S-SNEDDS中具有巨大应用潜力的新型聚合物载体。因此，在未来的研究中将继续采用所提出的方法，以确立S-SNEDDS作为其他无定形系统的替代制剂。
