Systematic development with quality by design approach of effervescent floating multiple unit minitablets of metoprolol succinate using hydrophobic grade of gelucire

Abstract

Objective: The objective of this study was to systematically develop with Quality by Design (QbD) approach of Effervescent Floating Multiple unit Minitablets (EFMM) of metoprolol succinate (MS) for once-a-day dosing using hydrophobic grade of gelucire in order to increase gastric residence time. Methods: Risk assessment using Failure Mode Effect Analysis (FMEA) was conducted and further screened using taguchi design. A Box-Behnken Design (BBD) was adopted for the process of optimization. The dissolution profile of optimised formulation was compared with the marketed formulation. Drug compatibility study and stability study were also conducted. Results: After conducting risk assessment and screening amount of gelucire 43/01(G 43/01), HPMC K15 M (HM) and NaHCO3 (SB) were found to be as significant factor. The process of optimisation results the single dose of EFMM MS consisting of 125 mg of G 43/01, 72 mg of HM and 28 mg of SB which shows an average of Floating Lag Time (FLT) within 3 min, Floating Time (FT) of 19 hr 36 min, time to release 50% of drug (t50) of 6 hr 38 min and time to release 90% of drug (t90) of 19 hr 12 min. The optimised formulation found to have better dissolution profile as compared to the marketed formulation. The stability study revealed no significant change in various parameters before and after storage. Conclusion: It can be concluded that an optimum combination of various excipient can be used to increase the gastric residence time, sustaining the drug release and ultimately achieve the desired objective of once-a-day dosing of MS.