SOLID STATE MANIPULATION OF TELMISARTAN VIA MECHANOCHEMICAL ACTIVATION WITH KAOLIN: AN ASSESSMENT OF BIOPHARMACEUTICAL PROPERTIES OF AMORPHOUS PHASE AND ITS PHYSICAL STABILITYAbstract
The objective behind this study is to investigate the affinity between a carboxylic model drug telmisartan and kaolin. Telmisartan was comilled in solid state with kaolin in different weight ratios and characterized by Fourier transform infrared spectroscopy, Differential scanning calorimetry, X-ray powder diffractometry, scanning electron microscopy to examine the extent of transformation from crystalline to amorphous state. XRD and SEM studies revealed complete amorphization of telmisartan on comilling with kaolin for 1 h at 1:2 ratio. FTIR study showed that on milling with kaolin, the free acid carbonyl peak of telmisartan at 1692.14 cm-1 was disappeared, and a new carboxylate peak at 1578.72 cm-1 appeared. This disappearance of acid carbonyl peak and appearance of new carboxylate peak indicating an acid-base reaction between the carboxylic acid of telmisartan and kaolin. DSC study stated that in the milled samples, the melting endotherm of telmisartan was gradually shifted to lower temperature, and the intensity, as well as sharpness of the endotherm, was decreased. In-vitro study showed greater dissolution of telmisartan from telmisartan-kaolin milled powder as compared to pure drug. Stability study revealed that on storage also kaolin-telmisartan bound state was physically stable and the amorphous state of telmisartan in milled powder was unchanged.
Manami Dhibar, Santanu Chakraborty and Madhusmruti Khandai
Formulation Development Research Unit, Department of Pharmaceutics, Dr. B. C. Roy College of Pharmacy & AHS., Durgapur, West Bengal, India.
08 October 2020
11 February 2021
24 May 2021
01 September 2021