Process Optimization of Methylphenidate Hydrochloride Extended Release Pellets by QbD

Abstract:

Objective: The aim of the present research work was to optimize the process of Methylphenidate Hydrochloride (HCl) Extended releasse (ER) pellets based on Quality by Design (QbD) principles. Materials and methods: Wurster (Bottom spray fluid bed coating) process was employed to develop ER pellets of Methylphenidate HCl. Impact of various process variables on drug layering process was assessed by using statistical interpretation such as ANOVA. A face centered central composite design (CCD) was employed to study the effect of independent variables (product temperature, atomization air pressure, fluidization air volume, and spray rate) on dependent variables (Fines, agglomerates, coating efficiency and assay). Fabricated pellets were characterized for various physicochemical parameters and stability studies. Results: Optimization was done by fitting experimental results to the software program (Design expert). The design space for process parameters and its influence on %fines, % agglomerates, coating efficiency and assay was developed. From the obtained results, 40°C ± 2°C as product temperature, 0.8-1.0 kg/cm² as atomization air pressure, 45-60 CFM as fluidization air volume and 2-6 g/min as spray rate were selected as the operating ranges for robust coating process, desired yield and quality of the product. The drug release from the optimized formulation followed first order kinetics and fickian diffusion process. There is no significant change observed during stability. Conclusion: It was concluded that the face centered central composite design facilitated the process optimization of Methylphenidate HCl ER pellets. The Methylphenidate HCl ER pellets were successfully developed by employing bottom spray fluid bed coating (Wurster) technique.

Key words: Methylphenidate HCl, Pellets, Central composite design, Process variables.