Preparation and Evaluation of Co-amorphous Formulations of Telmisartan-Amino Acids as a Potential Method for Solubility and Dissolution Enhancement.

Abstract

Telmisartan (TLM) is a potent antihypertensive drug with pH-dependent aqueous solubility. This work aimed to enhance the solubility and dissolution rate of TLM by the co-amorphous drug amino acid (AA) approach by combining TLM, with different types and ratios of AAs. The co-amorphous TLM-AA blends were prepared by freeze-drying and investigated for solid-state characteristics like the dissolution rate enhancement of TLM. Among the prepared co-amorphous formulations, TLM-arginine (ARG) exhibited the greatest enhancement in solubility with increasing the molar ratio of ARG. The TLM-ARG at 1:2 ratio showed about a 57-fold increase in solubility of TLM and the highest dissolution percentage in phosphate buffer (pH7.5) (100% in 20 minutes) compared to both crystalline TLM (20% in 60 min) and physical mixture. Powder XRD, DSC, FTIR analysis and SEM demonstrated the formation of amorphous form within the co-amorphous formulations. Only TLM:ARG (1:0.5) were stable at (40°C, 75% RH) for a minimum of 90 days. In conclusion, ARG was able to stabilize the amorphous form of TLM and enhances its aqueous solubility and dissolution. The 1:2 w/w ratio of TLM-ARG co-amorphous showed the best solubility and dissolution rate while the 1:0.5 w/w ratio showed the best stability.