Optimization Of Metformin Pulsatile Drug Delivery System Using Central Composite Design

Objective: The aim of the study was to create a pulsatile multiparticulate system of metformin to be optimized in the
delivery of chronotherapeutic drugs.
Methods: Metformin pulsatile beads were made and optimized based on the BoxBehnken design with polyvinylpyrrolidone
(PVP, X₁) and ethyl cellulose (EC, X₂) as the independent variables. The particle size, polydispersivity index (PDI),
entrapment efficiency, lag-time and drug release were analyzed.
Results: EC had a substantial effect on particle size, lag time and drug release whereas PVP primarily had an effect on
entrapment efficiency and matrix hydration. Per cent percentage of drug release was 68.4 ± 0.31 and 88.4 ± 0.48, and lag
time 0.5 ± 0.02 h to 4.5 ± 0.06 h. The MP4 formulation, which was optimized (PVP 1.0 mg, EC 6 mg) was found to have
a particle size of 1336.0 ± 3.6 nm, PDI of 0.794 + 0.06 and entrapment efficiency of 98.50 + 0.52, lag time of 0.5 + 0.03
h, and drug release of 88.4 + 0.48.
Conclusion: The optimized pulsatile system exhibited a short lag time with a rapid release of the drug, therefore, it can be
considered an effective chronotherapeutic delivery system of metformin