Novel Tanshinone II A ternary solid dispersion pellets prepared by a single-step technique: in vitro and in vivo evaluation

Abstract

Novel Tanshinone II A (TA) ternary solid dispersion (tSD) pellets with the combination of polyvinylpyrrolidone and poloxamer 188 as dispersing carriers were prepared by a single-step technique. A formulation screening study showed that the addition of poloxamer 188 to binary TA-PVP system could remarkably promote the dissolution rate of TA from 60% to 100% after 60 min. Scanning electron microscopy study revealed a smooth surface and a tightly packed coating structure. Differential scanning calorimetry analysis confirmed the formation of solid dispersions. In vivo test showed that TA tSD pellets presented significantly larger AUC(0-)(t), which was 0.76 times more than that of binary solid dispersion (bSD) pellets, 2.87 times more than that of physical mixtures (PMs) and 5.40 times more than that of TA. C(max) of TA tSD pellets also increased by 1.82-8.97-fold as that of bSD pellets, PMs and TA. TA tSD pellets generated obviously shortened T(max) of (3.80 ± 0.398)h, compared to bSD pellets with (4.15 ± 0.456)h, PMs with (4.65 ± 0.226)h and TA with (5.52 ± 0.738)h. In conclusion, the addition of poloxamer 188 to pellets containing PVP-based solid dispersions could achieve complete dissolution, accelerated absorption rate and superior oral bioavailability. The fluid-bed technique becomes an alternative approach to obtain solid dispersion-coated pellets.