Department of Physical Chemistry, Medical University of Gdansk, Gdansk, Poland.
Eur J Pharm Biopharm. 2013 Jan;83(1):114-21. doi: 10.1016/j.ejpb.2012.09.019. Epub 2012 Oct 17.
Telmisartan (TLM), a poorly water-soluble angiotensin II receptor antagonist in crystalline form, was transformed into the amorphous state by the melt quench technique, as well as a cryogenic grinding method, in order to improve its physiochemical properties. The chemical stability of TLM, that is, the tendency of the material to resist change or decomposition due to internal reaction, or due to the effects of air, heat, light, pressure, etc., during formation of the amorphous phase was assessed by monitoring high performance liquid chromatography. The existence of the amorphous state was confirmed by differential scanning calorimetry and X-ray powder diffraction. The glass transition occurred at T(g)=401K. In the next stage, the solubility of TLM in 0.1M HCl, phosphate buffer, pH=6.8, and water (25°C and 37°C) was determined. Both amorphous forms of TLM (vitrified and cryogrinded) had a higher solubility (μg/ml) than their crystalline counterpart. An important and interesting problem of the study was to evaluate how the tableting process was affected by the choice of either a crystalline or an amorphous form of TLM. Eight different tablet formulations were evaluated using both the crystalline and the amorphous form of TLM. Measurements of the physical properties and dissolution tests of G4 formulations tablets with telmisartan in crystalline and amorphous form after different storage periods were also performed.
替米沙坦（TLM）是一种水溶性差的结晶型血管紧张素 II 受体拮抗剂，通过熔融淬火技术和低温研磨方法转化为无定形态，以改善其物理化学性质。通过监测高效液相色谱法来评估 TLM 的化学稳定性，即材料由于内部反应或由于空气、热、光、压力等的影响而抵抗变化或分解的趋势，在形成无定形相时。通过差示扫描量热法和 X 射线粉末衍射法确认无定形态的存在。玻璃化转变发生在 T(g)=401K。在接下来的阶段，测定了 TLM 在 0.1M HCl、磷酸盐缓冲液、pH=6.8 和水中（25°C 和 37°C）的溶解度。两种 TLM 的无定形形式（玻璃化和低温研磨）的溶解度（μg/ml）均高于其结晶形式。研究的一个重要而有趣的问题是评估片剂制备过程如何受到选择 TLM 的结晶形式或无定形形式的影响。使用结晶形式和无定形形式的 TLM 评估了八种不同的片剂配方。还对 G4 配方片剂的物理性质测量和在不同储存期后用结晶和无定形形式的替米沙坦进行的溶解试验进行了评估。
