Isaac Jinu, Ganguly Swastika, Ghosh Animesh
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215, India.
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215, India.
Eur J Pharm Biopharm. 2016 Apr;101:43-52. doi: 10.1016/j.ejpb.2016.01.016. Epub 2016 Jan 29.
The aim of this study was to enhance the dissolution and bioavailability of telmisartan (TLM), a poorly water soluble drug by co-milling approach. Physical mixtures of TLM and poly(vinyl alcohol) (PVA) were co-milled in a planetary micro mill in a dry condition by varying process parameters such as drug to polymer weight ratio, ball-to-powder weight ratio, and rotational speed. The co-milled products offered cumulative percentage dissolution of TLM above 75% in 30 min (CG 1 and CG2). These samples were characterized using field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Raman spectra analysis. Well-dispersed acicular shaped particles of TLM were observed in co-milled products. A mixture of crystalline and amorphous TLM with a particle size less than 1 μm was present in CG1. The particle size of TLM observed in CG2 was less than 2 μm. In addition to crystalline and amorphous form of TLM, defective/disordered crystals of TLM were also present in CG 2. Therefore, CG2 tablets exhibited poor stability. CG 1 tablets were found to be stable under accelerated stability test conditions. The relative bioavailability of TLM of CG 1 containing tablets in comparison with Micardis® was 93.92±12.84% (in rabbits). Thus, co-milling of TLM with PVA proves to be a promising "alkalinizer free green approach" to ensure the dissolution and bioavailability of poorly water soluble TLM.
本研究的目的是通过共研磨方法提高替米沙坦（TLM）（一种水溶性差的药物）的溶出度和生物利用度。将TLM与聚乙烯醇（PVA）的物理混合物在行星式微型研磨机中于干燥条件下进行共研磨，通过改变药物与聚合物重量比、球与粉末重量比以及转速等工艺参数。共研磨产物在30分钟内使TLM的累积溶出百分比高于75%（CG 1和CG2）。使用场发射扫描电子显微镜（FE-SEM）、粉末X射线衍射（PXRD）、差示扫描量热法（DSC）和拉曼光谱分析对这些样品进行表征。在共研磨产物中观察到分散良好的针状TLM颗粒。CG1中存在粒径小于1μm的结晶和无定形TLM混合物。在CG2中观察到的TLM粒径小于2μm。除了TLM的结晶和无定形形式外，CG 2中还存在TLM的缺陷/无序晶体。因此，CG2片剂表现出较差的稳定性。发现CG 1片剂在加速稳定性试验条件下是稳定的。与美卡素®相比，含CG 1的片剂中TLM在兔体内的相对生物利用度为93.92±12.84%。因此，TLM与PVA的共研磨被证明是一种有前景的“无碱化剂绿色方法”，可确保水溶性差的TLM的溶出度和生物利用度。
