Cleaning Method Validation for Estimation of Dipyridamole Residue on the Surface of Drug Product Manufacturing Equipment Using Swab Sampling and by High Performance Liquid Chromatographic Technique.

Abstract

Cleaning validation is the procedure used to ensure that the cleaning process has eliminated the residues of drug substance from on the equipment surface after manufacture. A simple, sensitive, robust, and accurate high performance liquid chromatographic method was developed for the quantitative estimation of dipyridamole in swab samples obtained from the equipment surface after the manufacture of dipyridamole modified release capsules. The method was developed by using a Hypersil BDS C18 (150×4.6 mm, 5 μm) column with mobile phase containing a mixture of buffer (potassium dihydrogen phosphate buffer, pH 7.0±0.05) and methanol in the ratio of 30:70 v/v. Flow rate was 1.5 mL/min, column temperature was 45°C, and injection volume was 5 μL. The method was validated and a specificity study was conducted to prove that there was no interference from blank and swab blank at the retention time of dipyridamole. The limit of detection and limit of quantification (LOQ) were established by using a series of linearity solutions and were found to be 0.041 μg/mL and 0.124 μg/mL, respectively. The method precision at the LOQ level was 8.6% relative standard deviation (RSD), method precision was 0.2% RSD, and ruggedness was 0.3% RSD. The method was accurate from the concentration of 0.13 μg/mL to 21.80 μg/mL and the recovery results met the acceptance criteria. The linearity of the method was found from 0.12 μg/mL to 20.14 μg/mL and the r2 value was 0.997. The robustness for the flow rate, wavelength, column temperature, buffer pH, and mobile phase ratio variations was tested, and all the system suitability parameters were met. The method validation was performed as per the regulatory requirements and guidelines. The validation parameters met the acceptance criteria and the proposed method can be applied for the intended routine swab analysis.