替米沙坦固体分散体的含量测定及表征

目的建立替米沙坦-羟丙甲纤维素（HPMC）固体分散体中替米沙坦含量测定的反相高效液相色谱（RP-HPLC）法,并对其进行理化性质表征。方法以HPMC为载体,采用冷冻干燥法,制备替米坦固体分散体。色谱分析方法为Phenomenex C_（18）（4.6 mm×250 mm,5μm）色谱柱,流动相0.01 moL/L KH_2PO_4（磷酸调pH至3.7）-乙腈（40：60）,流速1.0 ml/min,检测波长298 nm,柱温35℃,进样量20μl。以X-射线衍射法（XRD）和差示扫描量热法（DSC）分析药物在载体中的存在状态。结果在本色谱条件下替米沙坦与辅料及溶剂峰分离良好,替米沙坦在1.0～100.0μg/ml质量浓度范围内与峰面积呈良好的线性关系（r=0.9999,n=8）,日内精密度试验的相对标准偏差（RSD）为0.52%～0.72%（n=5）,日间精密度试验的RSD为0.67%～1.79%（n=5）,回收率为98.79%～100.20%（n=3）。主药在固体分散体中是以无定型或分子状态存在。结论以HPMC为载体可以成功制备出替米沙坦固体分散体。RP-HPLC色谱分析简便、易行,可用于替米沙坦-HPMC固体分散体中替米沙坦的含量测定。

Content Determination and Characterization of Telmisartan Solid Dispersion

Objective To establish an RP-HPLC method for determination of drug content in telmi-sartan -HPMC solid dispersion and to evaluate the physicochemical properties of solid dispersions.Methods Telmisartan solid dispersion was prepared by a lyophilization method with HPMC as hydrophilic carrier. RP-HPLC analysis was performed on a Phenomenex C_（18）column（4.6mm×250mm,5μm） with mobile phase of 0.01 mol/L KH2PO4（pH 3.7,adjusted by phosphoric acid） - acetonitrile（40：60）. The flow rate was 1.0 ml/min.The UV detector wave length was set at 298 nm.The column compartment temperature was set at 35℃.The injection volume was 20μl.X-ray diffraction（XRD） and differential scanning calorimeter（DSC） was used to determine the status of telmisartan in solid dispersion.Results It had a good linear relation in the range from 1.0 to 100.0μg/ml（r=0.9999,n=8）.The intra-day precision（RSD） was from 0.52%to 0.72%（n=5）,the inter-day precision（RSD） was from 0.67% to 1.79%（n=5 ）,the recovery rate was from 98.79%to 100.20%（n=3）.Telmisartan existed as molecular or amorphous state in solid dispersion.Conclusion Telmisartan solid dispersion is sucessfully prepared with HPMC as a carrier.The developed method is simple,accurate and reliable for determination of the drug content in telmisartan-HPMC solid dispersion.