A QbD assisted modified release formulation of Midodrine Hydrochloride for management of long-term hypotension

Abstract

Midodrine Hydrochloride (MDH) is primarily utilized for the treatment of orthostatic hypotension. The main objective of this research work is to study the effect of the ratio of Methocel 4M to 100M, PVP K-30, and magnesium stearate in extended-release (ER) layer of bilayer tablets of MDH. Bilayer tablets of MDH were optimized by the design of experiment (DoE) using response surface face centre (α = 1), the central composite design having three independent variables at three levels. Bilayer tablets of MDH were administered once a day to reduce dosing frequency and improve patient compliance. Midodrine Hydrochloride tablets contain a drug layer and extended-release layer, which is further compressed into bilayer tablets. Based on the results of in-vitro %drug release it can be concluded that the ratio of Methocel 4M to 100M in MDH bilayer tablets shows a significant impact on % drug release whereas the concentration of PVP K-30 and concentration of magnesium stearate does not shows significant impact on % drug release. As the increase in the ratio of Methocel 4M to 100M, increase in the % drug release and as a decrease in the ratio of Methocel 4M to 100M, decrease in the % drug release. The optimized formulation of MDH bilayer tablets with 6% of Methocel 4M as an extended-release polymer, 24% of Methocel 100M as an extended-release polymer, 5% of PVP K-30 as a binder and 0.5% of magnesium stearate as a lubricant exhibits extended drug release up to 12 hours.