Enhanced Solubility of Telmisartan Phthalic Acid Cocrystals within the pH Range of a Systemic Absorption Site

Telmisartan (TLM), a nonpeptide angiotensin II antagonist, is widely prescribed for treating arterial hypertension and marketed by the innovator with the trade name of Micardis and Micardis plus. Telmisartan exhibits low aqueous solubility in the pH range of 3-7, which is the physiological pH. For addressing the issue of poor solubility of TLM, its commercial form makes use of inorganic alkalinizers. The present work illustrates the attempt to improve the solubility of telmisartan via a crystal engineering approach. A novel solid form of telmisartan with phthalic acid was obtained through the solution crystallization method (TPS) and the reaction crystallization method (TPR). Both the forms (TPS and TPR) were thoroughly characterized by powder diffraction X- ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and H-1 NMR and were identified to be two different crystalline forms. Solubility studies of TPS and TPR were conducted at varying pH of phosphate buffer, and they exhibited 11-fold and 22-fold increased solubility, respectively, when compared to that of the pure drug at pH 5, which is within the pH of small intestine at which telmisartan is best absorbed orally from the systemic circulation.