Quality by Design-basedStability-indicating Reverse Phase HighPerformance Liquid ChromatographyMethod Development and Validation forSimultaneous Estimation of TamsulosinHydrochloride and Tadalafil inPharmaceutical Dosage Forms

Abstract

A stability-indicating reverse phase high performance liquid chromatography (RP-HPLC) method based on the
analytical quality by design (AQbD) approach was developed and validated for the simultaneous estimation of
Tamsulosin (TAM) hydrochloride (HCl) and Tadalafil (TDL) in pharmaceutical formulations. An analytical target
profile was developed that specified the method performance requirements, and critical method parameters were
identified based on risk assessment, and optimized using a systematic experimental design. Chromatographic
separation was available on the C18 column with triethylamine buffer and methanol as the mobile phase
and detection was performed at 243 nm using ultraviolet. The method was validated as per the International
Conference on Harmonisation Q2(R1) guidelines for linearity, precision, accuracy, specificity, robustness, and
sensitivity. The method showed a good linearity within the studied concentration ranges with a correlation
coefficient of more than 0.999 for both analytes. Precision studies provided ≤2% relative standard deviation
values, indicating good repeatability, and intermediate precision and accuracy studies gave the recovery values
between >98% and 102%.The limits of detection were found to be 0.4 μg/mL for TAM HCl and 1.3 μg/mL
for TDL. Robustness evaluation revealed that slight changes of chromatographic conditions did not influence
the performance of the method to a great extent. Forced degradation studies under acidic, alkaline, oxidative,
thermal, and photolytic conditions ensured good separation of degradation products from the analyte peaks,
proving the stability-indicating ability of the method. The developed AQbD-driven RP-HPLC method is precise,
accurate, robust, and reliable, and thus can be used for routine quality control and stability studies of TAM HCl
and TDL in both dosage combinations