Method Development and Validation for Determining Formoterol Fumarate and Tiotropium in Tiomate Transcaps Dry Powder Inhaler

Tiotropium (TIO) and formoterol fumarate (FF) combination in dry powder inhaler dosage form is used in the treatment of asthma, bronchospasm, chronic bronchitis, emphysema and chronic obstructive pulmonary diseases (COPD). In order to develop the emerging and advancing dry powder inhaler combinations for enhanced therapeutics, it is necessary to have a sensitive, simple, robust and validated analytical method. A new HPLC method has been developed as an alternative to existing techniques for the determination of FF and TIO in combined formoterol fumarate dihydrate and tiotropium bromide monohydrate dry powder inhaler. The HPLC separation utilises isocratic elution using a mobile phase consisting of 0.2% triethylamine buffer (pH 2.5) with dilute O-phosphoric acid and acetonitrile (80:20% v/v) at 1.0 mL/min flow rate, 25°C column temperature, and PDA detector set at 228 nm wavelength, and Hypersil BDS C18 column (150 × 4.6 mm, 5 μm). The linearity test was performed in a concentration range from 0.50 to 3.02 ppm for TIO and 0.32 to 1.93 ppm for FF. The correlation coefficient ( R 2 ) was found to be 0.999 for both FF and TIO, and the % mean recovery at each concentration varied from 98.0 to 102.0% for both FF and TIO. Being validated in accordance with ICH guidelines, this method provides a safer and easier solution for QC testing and stability studies for the assay and other tests of dry powder inhalers including content uniformity, uniformity of delivered dose and fine particle dose tests.