Stable nimodipine tablets with high bioavailability containing NM-SD prepared by hot-melt extrusion

In the present study, using PVP/VA (Kollidon VA64) as a carrier, a nimodipine (NM) solid dispersion (SD) was prepared by hot-melt extrusion (HME). The effect of temperature during HME, the ratio of NM to Kollidon VA64 and the particle size of the SD after milling on the dissolution behavior were investigated. The temperatures of the extruder barrel zones and die were set as follows: Zone1 = 140 °C, Zone2 = 150 °C, Zone3 = 150 °C, Zone4 = 150 °C and Die = 100 °C. The drug content in SD was set at 15% and SD was milled to pass through a no. 40 mesh sieve. In combination with HME, nimodipine tablets (NM-T-SD (F 13)) were produced by direct compression, and the stability and related compounds of NM-T-SD (F 13) were studied. The results revealed that NM-T-SD (F 13) was stable during storage (40 °C, RH 75%) for six months and related compounds of NM-T-SD (F 13) accounted for less than 0.5% and no new related compounds were produced during HME, indicating that NM was able to tolerate the high temperature during HME. Finally, the bioavailability of NM-T-SD (F 11, F 13) was evaluated in beagle dogs with Nimotop® (Bayer Health Company LTD) and nimodipine tablets (NM-T-C) produced by The Central Pharmaceutical Co., Ltd (Tianjin, China) as references; the results showed similar C max and AUC 0 → 24 values for NM-T-SD (F 13) and Nimotop®, while the C max of NM-T-SD (F 11) was much lower than that of Nimotop® and provided evidence that Eudragit® EPO should not be used during HME because of its highly pH-dependent nature. Our present work demonstrated that, from a practical point of view, the pH-dependent nature of the carrier in SD should be focused on preparing immediate release dosage forms. [Display omitted]