Development of Paracetamol, Chlorpheniramine Maleate & Phenylephrine Hydrochloride syrup for Pediatric use & evaluation by applying QbD Approach to analytical RP-HPLC method

The present work is based on formulation & analytical method development of Paracetamol (PCM), Chlorpheniramine Maleate (CPM) & Phenylephrine Hydrochloride (PPH) syrup. A Fixed dose combination (FDC) of PCM, PPH & CPM are commonly used in clinical practice as antipyretic-analgesic drugs to treat pain & common cold conditions. The objective of the study is to develop a sugar free syrup formulation which have been smashing in market for pediatric use. The formulation of the product was done by using QbD based development, that has being significantly evolved by following the introduction of ICH guidelines such as Q8(R2), Q9, Q10, Q11 that offers comprehensive direction on implementation & breadth of QbD. The excipients were selected on the basis of the literature survey along with it preformulation studies was carried out to check compatibility on ingredients. The results showed that all active compounds are compatible with excipients. The method of EG-DEG content was developed & validated, in which precision and intermediate precisionwas checked by evaluating the %RSD of the verified method along with it specificity, accuracy was also performed that helps access unequivocally the analyte product & matrix components as well as to determine accuracy of the EG-DEG method, followed by linearity and robustness. The studies has also focused on development of precise, accurate & specific RP-HPLC stability demonstrating method for real-time estimation of PCM, PPH & CPM in formulation by implementing quality by design approach. The method parameters for HPLC, like flow rate and mobile phase composition, are identified as Critical Method Attributes (CMA). A design space was established using Design of Experiments (DoE) facilitated by design experts.The resolution amongst peaks were achieved on an YMC Triart C18 HPLC column (4.6 × 150 mm; 5 µm) at 220 nm, by upholding column oven temperature at 40°C. The optimized conditions included a gradient elution sodium phosphate buffer (pH 3.0) as a mobile phase A then composition of Acetonitrile: Methanol in the ratio of 70:30 as mobile phase B, maintaining flow 1.2 mL/min. Product was stable up to 6 months’ period with liner stability.