Effect of amorphization method on telmisartan solubility and the tableting process
Effect of amorphization method on telmisartan solubility and the tableting process
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DOI：
10.1016/j.ejpb.2012.09.019
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发表时间：
2013-01-01
影响因子：
4.9
通讯作者：
Guzik, L.
中科院分区：
文献类型：
--
作者：
Lepek, P.;Sawicki, W.;Guzik, L.
替米沙坦（TLM）是一种水溶性差的结晶形式的血管紧张素II受体拮抗剂，通过熔融骤冷技术以及低温研磨方法将其转化为非晶态，以改善其理化性质。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倾向，通过监测高效液相色谱来评估非晶相形成期间的温度。用差示扫描量热法和X射线粉末衍射法证实了非晶态的存在，玻璃化转变温度为401 K。在下一阶段，测定TLM在0.1M HCl、磷酸盐缓冲液（pH = 6.8）和水（25 ℃和37 ℃）中的溶解度。两种无定形形式的TLM（玻璃化的和冷冻研磨的）具有比它们的结晶对应物更高的溶解度（μ g/ml）。该研究的一个重要且有趣的问题是评估压片过程如何受到TLM的结晶或无定形形式的选择的影响。使用TLM的结晶和无定形形式评估八种不同的片剂制剂。还对不同储存期后含有结晶和无定形替米沙坦的G4制剂片剂进行了物理性质测定和溶出度试验。(C)2012爱思唯尔有限公司版权所有。
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 = 401 K. In the next stage, the solubility of TLM in 0.1 M HCl, phosphate buffer, pH = 6.8, and water (25 degrees C and 37 degrees C) was determined. Both amorphous forms of TLM (vitrified and cryogrinded) had a higher solubility (mu g/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. (C) 2012 Elsevier B.V. All rights reserved.