Co-milling of telmisartan with poly(vinyl alcohol)--An alkalinizer free green approach to ensure its bioavailability.

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.