Application of Qbd Principles to Develop and Validate a Method for Cinacalcet Determination in Api and Its Dosage Form

Abstract

Introduction: Cinacalcet Hcl [CIN] is used to treat hyperthyroidism and hypercalcisim. and improves the sensitivity of calcium receptors on parathyroid cells to reduce parathyroid harmone levels and hence decrease serum calcium levels. It also has a role in hypercalcemia and kidney disease (CKD) in persons with parathyroid cancer.

Objectives:QbD approach used to assess risk and develop cleaning method for Cinacalcet HCl.So far no methods were reported for estimation of the same

Methods:The method operable design region (MODR) was obtained by CCD concluded from surface and contour plot Analytical Target Profile defined with 15 variables verified for quality. The contour diagram displays the anticipated and optimized data, which includes the composition of the eluent phase consisting of potassium dihydrogen ortho Phosphate buffer with a pH of 3.5 and acetonitrile (CH₃CN) in a ratio of 20:80 v/v. The flow rate was set at 1 mL/min for a duration of 10 minutes. The analysis was performed using a Kinetex C₁₈ column at a temperature of 25 °C, and the wavelength chosen for detection was 279 nm.

Results:After injecting swabbed samples from SS plate(10*10 cm), sharp and resolved peak of CIN at 2.8 minutes of retention [RT] , was observed. The set method had a LOQ of 0.740 µg mL−1 and a LOD of 0.244 µg mL−1.The measured linearity of the calibration curve ranges from 0.25 to 12.5 gmL^-1, with a r² of 0.999. All validation parameter findings fell within the permitted range.% RSD of system suitability 0.03 %, inter-day and intra-day precision % RSD value 1.07&0.95%, respectively, and accuracy (0.059–0.189)%. Percentage purity was found as 101.16.

Conclusion: QbD approach is applied effectively to optimize HPLC method for CIN estimation in formulation and API manufacturing.