Department of Industrial Pharmacy, Faculty of Pharmacy, University of Alexandria, 1 El-Khartoum Square, El-Azarita, Alexandria, Egypt.
Drug Dev Ind Pharm. 2011 Apr;37(4):446-55. doi: 10.3109/03639045.2010.522190.
Flutamide (FLT) has poor aqueous solubility and low oral bioavailability.
Lyophilization monophase solution was used for preparing lyophilized dispersions of FLT with polyols and amino acids to increase its poor dissolution.
Physical properties and dissolution behavior of their physical mixtures and lyophilized dispersions were investigated.
The carriers increased the aqueous solubility of FLT but to a limited extent with arginine and glycine showing a linear A(L)-phase solubility diagrams. Gas chromatography indicated that residual tertiary butyl alcohol was in range of 0.007-0.023% (w/w) in the dispersions. In all dispersions, the crystal structure of FLT was confirmed using differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy. However, the percent drug crystallinity was found to decrease with increasing the carrier content. Infrared spectroscopy revealed no interaction between drug and carriers. The particle size of FLT dispersions ranged between 0.61 and 1.81 μm, with a high surface area (293.93-465.37 m(2)/g) and porosity (447.69-754.33 e(-3) mL/g). In addition, the poor flow properties of FLT were improved but to a limited extent. FLT dissolution from the dispersions was enhanced with 46.35% and 36.43% of FLT dissolved after 30 minutes from 1:5 FLT-mannitol and FLT-trehalose dispersions, respectively, compared with only 13.45% of pure FLT. On the other hand, after 30 minutes 38.57% and 46.78% of FLT was dissolved from 1:3 FLT-arginine and FLT-glycine dispersions, respectively.
These data suggest that polyols and amino acids might be useful adjuncts in preparation of immediate-release formulations of FLT.
氟他胺（FLT）水溶性差，口服生物利用度低。
利用单相溶液法将 FLT 与多元醇和氨基酸制成冻干分散体，以增加其溶解度。
考察了物理混合物和冻干分散体的物理性质和溶解行为。
载体增加了 FLT 的水溶性，但程度有限，精氨酸和甘氨酸呈线性 A（L）-相溶解度图。气相色谱表明，分散体中残留的叔丁醇量在 0.007-0.023%（w/w）之间。在所有分散体中，均采用差示扫描量热法、X 射线衍射法和扫描电子显微镜法确认了 FLT 的晶体结构。然而，随着载体含量的增加，药物结晶度的百分比有所下降。红外光谱显示药物与载体之间没有相互作用。FLT 分散体的粒径在 0.61-1.81μm 之间，比表面积（293.93-465.37m2/g）和孔隙率（447.69-754.33e-3mL/g）较高。此外，FLT 的流动性较差，但在一定程度上有所改善。与纯 FLT 相比，在 30 分钟后，FLT-甘露醇和 FLT-海藻糖分散体中分别有 46.35%和 36.43%的 FLT 溶解，FLT 溶出度分别提高了 46.35%和 36.43%。另一方面，在 30 分钟后，FLT-精氨酸和 FLT-甘氨酸分散体中分别有 38.57%和 46.78%的 FLT 溶解。
这些数据表明，多元醇和氨基酸可能是制备 FLT 速释制剂的有用辅料。
