Demonstration Progressive Statistical and Analytical Tools to Optimize Febuxostat - MCC - Pearlitol - Kyron Multi Particulate System (FBX-MPK-MPS)

Microcrystalline cellulose (MCC) is widely recognized as benchmark extruder aid for pellet design. Major drawback of MCC is that partial drug release confines its use to an instant-release formulation. That draws attention to exploring novel excipients as extrusion aids in combination with MCC. The current research aimed to explore excipients Pearlitol SD-100 and Kyron T-134 in development of FBX-MPK-MPS using extrusion-spheronization method, employing systematic and scientific approach. Extrusion-pelletization technique was used to formulate pellets. Pellets were optimized using a 32 full factorial design, with MCC: Pearlitol SD-100 (PSD) and Kyron T-134 (KT-134) as critical material attributes, and disintegration time, percentage drug release at 30min, and aspect ratio as responses. A grid search analysis was adopted to validate model. Optimal FBX-MPK-MPS was chosen considering range of responses to be measured using Design-Expert software. FBX-MPK-MPS were characterized and evaluated. FBX-excipient study revealed conversion of FBX crystalline to an amorphous form, which improved dissolution rate. FBX-MPK-MPS had good flowability with spherical shape and smooth surfaces. FBX-MPK-MPS size was found between 0.8 to 1.2mm. Friability and FBX content were found to be within the pharmacopoeial limits. 1:3 (MCC: PSD) and 12.5 mg PSD were found to be optimum for achieving desired results in terms of disintegration time (205 sec), %FBX release in 30min (96.53%), and aspect ratio (1.02). FBX-MPK-MPS with shortest disintegration time and immediate FBX release were successfully prepared and developed using QbD. Type and amount of excipients dictated release of FBX from FBX-MPK-MPS. Using PSD with MCC significantly affected disintegration time.