Guangzhou Higher Education Mega Center, Guangdong Pharmaceutical University, No. 280 Waihuandong Road, Guangzhou, China.
Department of Pharmaceutics, School of Pharmacy, Guangzhou Higher Education Mega Center, Guangdong Pharmaceutical University, No. 280 Waihuandong Road, Guangzhou, 510006, China.
AAPS PharmSciTech. 2018 Apr;19(3):1308-1319. doi: 10.1208/s12249-017-0936-5. Epub 2018 Jan 16.
The present study was intended to develop a controlled released osmotic pump capsule based on Nimodipine (NM)-loaded self-microemulsifying drug delivery systems (SMEDDSs) in order to improve the low oral bioavailability of NM. To optimize the NM-loaded SMEDDS composition, the experiments of NM solubility in different oils, the pseudo-ternary phase diagram experiments and the different drug loading experiments were conducted in the preliminary screening studies. Controlled release of NM required an osmotic pump capsule comprising a coated semi-permeable capsule shell, plasticizer, and pore-forming agent. NM release follows zero-order kinetics after oral administration. Polyethylene glycol content, used as a pore-forming agent, coating mass, and drug release orifice size were key factors affecting drug release behavior according to the single methods and were optimized through response surface methodology. The NM-loaded SMEDDS droplet size and the H NMR mass spectrogram of the novel capsule were determined. The droplet size of the reconstituted microemulsion was 39.9 nm and H NMR analysis showed NM dissolution in the microemulsion. The dissolution test performed on three batches of NM-SMEDDS capsules-prepared using optimal preparation methods-indicated the capsule to deliver a qualified drug delivery with a zero-order release rate. The results demonstrated that NM-loaded SMEDDSs were successfully developed and displayed a qualified release rate in vitro.
本研究旨在开发一种基于尼莫地平（NM）负载自微乳药物传递系统（SMEDDS）的控释渗透泵胶囊，以提高 NM 的口服生物利用度。为了优化 NM 负载 SMEDDS 的组成，在初步筛选研究中进行了 NM 在不同油中的溶解度实验、伪三元相图实验和不同载药量实验。NM 的控释需要包含包衣半渗透胶囊壳、增塑剂和致孔剂的渗透泵胶囊。NM 口服后释放遵循零级动力学。根据单因素法，聚乙二醇（PEG）作为致孔剂的含量、包衣质量和药物释放孔口大小是影响药物释放行为的关键因素，并通过响应面法进行了优化。测定了载 NM SMEDDS 的液滴大小和新型胶囊的 H NMR 质谱图。重建微乳的液滴大小为 39.9nm，H NMR 分析表明 NM 溶解在微乳中。对三批采用最佳制备方法制备的 NM-SMEDDS 胶囊进行的溶出度试验表明，该胶囊具有合格的零级释放速率的药物传递。结果表明，NM 负载 SMEDDS 已成功开发，并在体外显示出合格的释放速率。
