Implementation of QbD Approach to the Analytical Method Development and Validation for the Estimation of Propafenone Hydrochloride in Tablet Dosage Form

Chromatographic and spectrophotometric methods were developed according to Quality by Design (QbD) approach as per ICH Q8(R2) guidelines for estimation of propafenone hydrochloride in tablet dosage form. QbD approach was carried out by varying various parameters and these variable parameters were designed into Ishikawa diagram. The critical parameters were determined by using principal component analysis as well as by observation. Estimated critical parameters in HPTLC method include solvent methanol, mode of detection absorbance, precoated aluminium backed TLC plate (10？cm 10？cm), wavelength: 250？nm, saturation time: 20？min, band length: 8？mm, solvent front: 70？mm, volume of mobile phase: 5？mL, type of chamber: 10？cm 10？cm, scanning time: 10？min, and mobile phase methanol？:？ethyl acetate？:？triethylamine (1.5？:？3.5？:？0.4？v/v/v). Estimated critical parameters in zero order spectrophotometric method were solvent methanol, sample preparation tablet, wavelength: 247.4？nm, slit width: 1.0, scan speed medium, and sampling interval: 0.2, and for first order derivative spectrophotometric method it was scaling factor: 5 and delta lambda 4. The above methods were validated according to ICH Q2(R1) guidelines. Proposed methods can be used for routine analysis of propafenone hydrochloride in tablet dosage form as they were found to be robust and specific. 1. Introduction Quality by Design approach suggests looking into the quality of analytical process during the development stage itself. It says that quality should be built into the process design rather than testing into final results of analytical process [1]. QbD is defined as “a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding based on sound science and quality risk management” [2]. In alignment with the approach proposed in the draft FDA guidance for process validation, a three-stage approach [3] can be applied to method validation. Stage 1. Method Design. Define method requirements and conditions and identify critical controls. Stage 2. Method Qualification. Confirm that the method is capable of meeting its design intent. Stage 3. Continued Method Verification. Gain ongoing assurance to ensure that the method remains in a state of control during routine use. A critical function of Stage 1 is the design of an Analytical Target Profile (ATP) for the method. To design the ATP, it is necessary to determine the characteristics that will be indicators of method performance for its intended use. These are selected from the performance