Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning Province, China.
Liao Ning University, No.66, Chongshan Middle Road, Huanggu District, Shenyang City, Liaoning Province, China.
AAPS PharmSciTech. 2018 Oct;19(7):3057-3066. doi: 10.1208/s12249-018-1119-8. Epub 2018 Aug 8.
The objective of this study was to prepare ibuprofen enteric-coated sustained-release pellets (IB-SRPs) and codeine phosphate immediate-release pellets (CP-IRPs) to play a synergistic role in analgesia. The pellets were developed by extrusion-spheronization and fluidized bed coating technology. The single-factor investigation was used to determine the optimal prescription and process. The sustained-release membrane of IB-SRPs was water-insoluble ethyl cellulose (EC), triethyl citrate (TEC) was used as plasticizer, and hydroxypropyl methylcellulose (HPMCP) was chose as porogen. Besides, the immediate-release layer of CP-IRPs was gastric-soluble coating film. The ibuprofen and codeine phosphate compound capsules (IB-CP SRCs) were prepared by IB-SRPs and CP-IRPs packed together in capsules with the optimum doses of 200 and 13 mg, respectively. The prepared pellets were evaluated by scanning electron microscopy and dissolution test. Pharmacokinetic studies in beagle dogs indicated that the optimized IB-CP SRCs had smaller individual differences and better reproducibility comparing with commercial available tablets. Additionally, IB-CP SRCs achieved consistency with in vivo and in vitro tests. Therefore, IB-CP SRCs could play a great role in rapid and long-term analgesic.
本研究旨在制备布洛芬肠溶缓释微丸（IB-SRPs）和磷酸可待因速释微丸（CP-IRPs），以发挥协同镇痛作用。采用挤出滚圆和流化床包衣技术制备微丸。采用单因素考察法确定最佳处方和工艺。IB-SRPs 的缓释膜为不溶于水的乙基纤维素（EC），选用柠檬酸三乙酯（TEC）作为增塑剂，羟丙甲纤维素（HPMCP）作为致孔剂。此外，CP-IRPs 的速释层为胃溶包衣膜。将 IB-SRPs 和 CP-IRPs 以最佳剂量 200 和 13mg 分别装入胶囊中，制备布洛芬和磷酸可待因复方胶囊（IB-CP SRCs）。通过扫描电子显微镜和溶出度试验对制备的微丸进行评价。在比格犬体内药代动力学研究表明，与市售片剂相比，优化后的 IB-CP SRCs 个体差异较小，重现性更好。此外，IB-CP SRCs 体内外试验结果一致。因此，IB-CP SRCs 在快速和长期镇痛方面可能发挥重要作用。
