SBA-15增溶非洛地平的双层渗透泵片的制备

Preparation for bi-layer osmotic pump tablets of felodipine solubilized by SBA-15

目的:用介孔材料SBA-15改善非洛地平(felodipine,FDP)的水溶性,并结合双层渗透泵技术控制药物的释放。方法:通过溶剂挥发法将FDP载入SBA-15介孔孔道中制备固体分散体(FDP-SBA-15)。使用透射电镜观察SBA-15的形态结构,采用差示扫描量热法(differential scanning calorimetry,DSC),X射线衍射法(X-ray diffraction,XRD)和傅里叶红外光谱法(Fourier transform infrared spectroscopy,FTIR)表征药物在介孔孔道中的存在状态。利用溶出试验考察SBA-15对FDP的增溶能力和双层渗透泵片的体外释放度。通过高相液相色谱法(HPLC)测得双层渗透泵片和市售缓释片在体内药动学参数。结果:SBA-15能显著抑制药物结晶度,使药物以无定型形式存在。溶出试验表明SBA-15明显提高了FDP的溶出速率,双层渗透泵技术有效地控制了药物释放。体内试验表明自制的双层渗透泵片的口服生物利用度明显提高。结论:固体分散体与双层渗透泵技术联合在有效改善难溶性药物水溶性的同时,控制药物释放,提高口服吸收。

Objective： To improve the water solubility of felodipine （FDP） with mesoporous material SBA- 15, and control the drug release by combining bi-layer osmotic pump technology. Methods： FDP was loaded into the mesopores of SBA-15 with solvent evaporation method to prepare the solid dispersion （FDP-SBA-15）. The mor- phology and structure of SBA-15 were observed by using transmission electron microscopy （TEM）. The existing state of FDP in mesoporous pore was characterized by differential scanning calorimetry （ DSC）, X-ray diffraction （XRD） and Fourier transform infrared spectroscopy （FTIR）. The solubilization ability of SBA-15 for FDP and the release of bi-layer osmotic pump tablets in vitro were investigated by dissolution test. The pharmacokinetic parame- ters in vivo of bi-layer osmotic pump tablets and commercially available sustained-release tablets were measured by high performance liquid chromatography （HPLC）. Results： SBA-15 could significantly inhibit the crystallinity of the drug, and FDP existed in amorphous form. The dissolution test showed that SBA-15 significantly increased the dissolution rate of FDP, and the bi-layer osmotic pump technology effectively controlled the drug release. The in vi- vo experiments showed that the oral bioavailability of self-made bi-layer osmotic pump tablets was significantly im- proved. Conclusion： The combination of solid dispersion and bi-layer osmotic pump technology can improve the water solubility of insoluble drugs, control their release, and increase their oral absorption.