NIFEDIPINE 固體分散相之熱分析法和溶離特性探討   全文下載

Thermal Analysis and Dissolution Characteristics of Nifedipine Solid Dispersions

本研究以兩種親水性載体系統Gelucire（44/14）/PEG 600和PVP（K12-K25）/PEG 6000使用熔化或熔化／溶媒法比較熱分析法來製備nifedipine固體分散相，結果顯示在超過50%的比例與Nifedipine經過高溫熔化以後可以抑制結晶的產生而形成非晶型的狀態，且隨著載体的比例增加而增多。PEG 6000與Nifedipine以3 : 1的比例混合時，可以使Nifedipine的熔點降低到110°C。由溶離度測試的結果可以發現，經過與載体系統熔化處理後的Nifedipine溶離速率都比未經處理的還快。在Gelucire（44/14）/PEG 600系統，溶離的速率在加熱到高溫熔化的系列比在Gelucire熔點混合的快，溶離的速率也會隨著Gelucire含量的增加而加快。而對於PEG 6000 / PVP載体系統，當PVP和PEG 6000量增加，Nifedipine的溶離速率越快；然而溶離速率會因PVP分子量增加而延緩。

Solid dispersions of nifedipine prepared with two hydrophilic carrier systems, Gelucire (44/14)/PEG 600 and PVP (K12-K25)/PEG 6000 by fusion or fusion/solvent method were characterized by thermal analysis for comparisons. Results demonstrated that both carrier systems were able to prohibit the crystallization of nifedipine after the mixture melted at a higher temperature at a ratio exceeding 50%. The extent of forming amorphous nifedipine due to the inhibition of crystallization, also raised with the increasing ratio of the carrier. When mixing with PEG 6000 at a ratio of 3 : 1, the melting temperature of nifedipine dropped to 110°C. Dissolution tests further demonstrated that nifedipine, once fused with these carriers, possessed an enhanced dissolution rate. As to the Gelucire (44/14)/PEG 600 system, the dissolution rates from those samples prepared at a higher temperature were faster than those prepared at the melting point of Gelucire. The dissolution rate increased with the amount of Gelucire added in the preparation. For the PVP/PEG 6000 carrier system, the dissolution rate of nifedipine increased with the amounts of both PVP and PEG 6000. However, a slower dissolution rate was also noted resulted from higher molecular weight of PVP.