Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 162-1 Songdo-dong, Yeonsu-gu, Incheon 406-840, Republic of Korea.
Int J Pharm. 2013 Jan 30;441(1-2):50-5. doi: 10.1016/j.ijpharm.2012.12.020. Epub 2012 Dec 20.
Telmisartan is a biopharmaceutical classification system (BCS) class II drug that has extremely low water solubility but is freely soluble in highly alkalized solutions. Few organic solvents can dissolve telmisartan. This solubility problem is the main obstacle achieving the desired bioavailability. Because of its unique characteristics, the supercritical anti-solvent (SAS) process was used to BCS class II drug in a variety of ways including micronization, amorphization and solid dispersion. Solid dispersions were prepared using hydroxypropylmethylcellulose/polyvinylpyrrolidone (HPMC/PVP) at 1:0.5, 1:1, and 1:2 weight ratios of drug to polymer, and pure telmisartan was also treated using the SAS process. Processed samples were characterized for morphology, particle size, crystallinity, solubility, dissolution rate and polymorphic stability. After the SAS process, all samples were converted to the amorphous form and were confirmed to be hundreds nm in size. Solubility and dissolution rate were increased compared to the raw material. Solubility tended to increase with increases in the amount of polymer used. However, unlike the solubility results, the dissolution rate decreased with increases in polymer concentration due to gel layer formation of the polymer. Processed pure telmisartan showed the best drug release even though it had lower solubility compared to other solid dispersions; however, because there were no stabilizers in processed pure telmisartan, it recrystallized after 1 month under severe conditions, while the other solid dispersion samples remained amorphous form. We conclude that after controlling the formulation of solid dispersion, the SAS process could be a promising approach for improving the solubility and dissolution rate of telmisartan.
替米沙坦是一种生物药剂学分类系统（BCS）Ⅱ类药物，其水溶性极低，但在高度碱性溶液中可自由溶解。很少有有机溶剂可以溶解替米沙坦。这种溶解度问题是实现所需生物利用度的主要障碍。由于其独特的特性，超临界抗溶剂（SAS）工艺被用于多种方式的 BCS Ⅱ类药物，包括微粉化、无定形化和固体分散体。使用羟丙基甲基纤维素/聚乙烯吡咯烷酮（HPMC/PVP）以药物与聚合物 1:0.5、1:1 和 1:2 的重量比制备固体分散体，并使用 SAS 工艺处理纯替米沙坦。对处理后的样品进行形态、粒径、结晶度、溶解度、溶出速率和多晶型稳定性的表征。经过 SAS 处理后，所有样品均转化为无定形形式，且确认其粒径为数百纳米。与原料药相比，溶解度和溶出速率均有所提高。溶解度随着聚合物用量的增加而增加。然而，与溶解度结果不同的是，由于聚合物凝胶层的形成，溶出速率随着聚合物浓度的增加而降低。与其他固体分散体相比，经过处理的纯替米沙坦的药物释放效果最好，尽管其溶解度较低；然而，由于处理后的纯替米沙坦中没有稳定剂，在恶劣条件下放置 1 个月后会重新结晶，而其他固体分散体样品仍保持无定形状态。我们得出结论，在控制固体分散体配方后，SAS 工艺可能是提高替米沙坦溶解度和溶出速率的一种有前途的方法。
