Murali Mohan Babu G V, Prasad Ch D S, Ramana Murthy K V
Division of Industrial Pharmacy, Department of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530003, India.
Int J Pharm. 2002 Mar 2;234(1-2):1-17. doi: 10.1016/s0378-5173(01)00925-5.
Modified gum karaya (MGK), a recently developed excipient was evaluated as carrier for dissolution enhancement of poorly soluble drug, nimodipine (NM). The advantages of MGK over the parent gum karaya (GK) were illustrated by differences in the in vitro dissolution profiles of respective solid mixtures prepared by co-grinding technique. The influence of process variable, such as polysaccharide concentration and method of preparation of solid mixture on dissolution rate was studied. Solubility studies were also performed to explain the differences in dissolution rate. Solid mixtures were characterized by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD) and scanning electron microscopy (SEM). The dissolution rate of NM was increased as the MGK concentration increased and optimum ratio was found to be 1:9 w/w ratio (NM:MGK). It is found that method of preparation of solid mixtures was significantly effected the dissolution rate of NM from solid mixtures. The order of method of preparation in according to their Dissolution Efficiency is physical mixture < co-grinding mixture < swollen carrier mixture < kneading mixture (water as kneading agent) < kneading mixture (70% v/v ethanol as kneading agent) < solid dispersion. Though, the solid mixtures prepared by other methods like solid dispersion, swollen carrier mixture and kneading technique gave faster release, co-grinding mixture prepared in 1:9 w/w ratio (NM:MGK) was found to exhibit a significant improvement in dissolution rate without requiring addition of organic solvents or high temperatures for its preparation and the process is less cumbersome. Hence, co-grinding technique appears to be more easier and the most convenient method from a practical point of view.
改性刺梧桐树胶(MGK)是一种最近开发的辅料,被评估作为难溶性药物尼莫地平(NM)溶出度增强的载体。通过共研磨技术制备的各自固体混合物的体外溶出曲线差异,说明了MGK相对于母体刺梧桐树胶(GK)的优势。研究了工艺变量,如多糖浓度和固体混合物制备方法对溶出速率的影响。还进行了溶解度研究以解释溶出速率的差异。通过差示扫描量热法(DSC)、X射线衍射研究(XRD)和扫描电子显微镜(SEM)对固体混合物进行了表征。随着MGK浓度的增加,NM的溶出速率提高,最佳比例为1:9 w/w比例(NM:MGK)。发现固体混合物的制备方法显著影响NM从固体混合物中的溶出速率。根据溶出效率,制备方法的顺序为物理混合物<共研磨混合物<溶胀载体混合物<捏合混合物(水作为捏合剂)<捏合混合物(70% v/v乙醇作为捏合剂)<固体分散体。虽然,通过固体分散体、溶胀载体混合物和捏合技术等其他方法制备的固体混合物释放更快,但发现以1:9 w/w比例(NM:MGK)制备的共研磨混合物在溶出速率上有显著提高,且制备过程无需添加有机溶剂或高温,并且该过程不太繁琐。因此,从实际角度来看,共研磨技术似乎更容易且是最方便的方法。