A physically stabilized amorphous solid dispersion of nisoldipine obtained by hot melt extrusion

• Published in: Powder technology 2016-11, Vol.301, p.342-348
• Main Authors: Fu, Qiang, Fang, Mingming, Hou, Yanxian, Yang, Wenqian, Shao, Jingbo, Guo, Mengran, Li, Mo, Li, Jingru, Wang, Yongjun, He, Zhonggui, Sun, Jin
• Format: Article
• Language: English
• Subjects: Amorphous solid dispersion; Hot melt extrusion; Nisoldipine; Pharmacokinetics; Physical stability
• ISSN: 0032-5910; 1873-328X
• DOI: 10.1016/j.powtec.2016.06.032

Nisoldipine is widely used clinically as an antihypertensive agent, however, its oral bioavailability and therapeutic effects are hindered by its very low solubility in water. The present study aimed to develop an amorphous solid dispersion (ASD) for nisoldipine, using hot melt extrusion, to increase or equilibrate with the in vitro dissolution and in vivo oral absorption of Nierxin, its commercial tablet formulation. The final preparation was prepared with Kollidon VA64 at a drug polymer weight ratio of 1:10. The amorphous state was confirmed by powder X-ray diffractometry, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. This ASD exhibited a higher dissolution profile than Nierxin and its physical mixtures. It maintained an amorphous state when stored at 60°C over 10days, however, the hydrogen bonds between nisoldipine and Kollidon VA64 were disrupted and its dissolution slightly reduced when stored at RH 92.5% for 10days. The pharmacokinetic study carried out in beagle dogs demonstrated that the ASD was bioequivalent to Nierxin. The results of this study suggest that ASD prepared by hot melt extrusion can be used as a suitable alternative to Nierxin in the future. [Display omitted] •An amorphous nisoldipine solid dispersion was prepared by hot melt extrusion.•This formulation showed a higher dissolution profile than the commercial tablets.•It was physically stable, but a moisture-proof packaging is suggested.•This formulation was bioequivalent to the commercial tablets.•It was an effective alternative for a nisoldipine immediate-release formulation.