School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
Eur J Pharm Biopharm. 2012 Nov;82(3):534-44. doi: 10.1016/j.ejpb.2012.06.016. Epub 2012 Sep 5.
The objective of this study was to prepare amorphous fenofibrate (FB) solid dispersions using thin film freezing (TFF) and to incorporate the solid dispersions into pharmaceutically acceptable dosage forms. FB solid dispersions prepared with optimized drug/polymer ratios were characterized by modulated differential scanning calorimetry (MDSC), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) specific surface area measurements, Fourier-transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), and supersaturation dissolution testing. Furthermore, a dry granulation technique was used to encapsulate the TFF compositions for in vitro dissolution and in vivo animal pharmacokinetic studies. The results showed that the TFF process produced amorphous, porous, microstructured, and stable solid dispersions with high surface areas. Development of solid oral dosage forms revealed that the performance of the FB containing solid dispersions was not affected by the formulation process, which was confirmed by DSC and XRD. Moreover, an in vivo pharmacokinetic study in rats revealed a significant increase in FB absorption compared to bulk FB. We confirmed that amorphous solid dispersions with large surface areas produced by the TFF process displayed superior dissolution rates and corresponding enhanced bioavailability of the poorly water-soluble drug, FB.
本研究的目的是采用薄膜冷冻（TFF）法制备非晶态非诺贝特（FB）固体分散体，并将其纳入可接受的药用剂型中。采用优化的药物/聚合物比例制备的 FB 固体分散体通过调制差示扫描量热法（MDSC）、粉末 X 射线衍射（XRD）、扫描电子显微镜（SEM）、BET 比表面积测定、傅里叶变换衰减全反射红外光谱（FTIR-ATR）和超饱和溶解试验进行了表征。此外，还采用干法制粒技术对 TFF 组合物进行包封，用于体外溶出度和体内动物药代动力学研究。结果表明，TFF 工艺可制备出具有高比表面积的非晶态、多孔、微结构且稳定的固体分散体。固体口服剂型的开发表明，FB 含固体分散体的制剂工艺不受影响，这通过 DSC 和 XRD 得到了证实。此外，大鼠体内药代动力学研究表明，与 FB 原料药相比，FB 吸收显著增加。我们证实，TFF 工艺制备的具有大比表面积的非晶态固体分散体具有更高的溶解速率和相应提高的难溶性药物 FB 的生物利用度。
