Optimization of Formulations of Metoprolol Succinate Tablets Containing Ofada Rice Starch Acetate as Tablet Matrix for Sustained Release Using Response Surface Methodology

Abstract

Background: Release-retarding polymers in matrix tablets play a vital role in controlling drug release from tablets.
Objectives: To prepare metoprolol succinate tablets by direct compression using Ofada rice (Oryza glaberrima Steud) starch acetate, degree of substitution (DS) 2.22, as a matrix for sustained release.
Materials and methods: The central composite design and response surface methodology were applied to evaluate the interactive effects of three variables: percent content of starch acetate (X₁), compression pressure (X₂) and compression time (X₃), on tablet crushing strength, friability and dissolution time (t₈₀).
Results: Crushing strength was 90.0 to 140.50 N; Friability 0.05 to 0.90 % and t80 5.75 to 11.50 h. X₁ and X₂ had significant effects on crushing strength and dissolution time (p < 0.0001). The interactions between X1 and X2 and those between X₁ and X₃ were significant on crushing strength and dissolution time, and on friability respectively (p < 0.0001). The correlation coefficients indicated that the regression model represented the experimental data well (R² = 0.9971 and R² (Adj) = 0.9944 for crushing strength; R² = 0.9976 and R2 (Adj) = 0.9954 for friability; R² = 0.9979 and R² (Adj) = 0.9961 for t₈₀). Optimized conditions for formulation of metoprolol succinate tablets were 60 %w/w Ofada starch acetate; 150 MNm^-2 compression pressure and 60 s compression time.
Conclusion: Optimized formulations of metoprolol tablets containing Ofada starch acetate with good mechanical strength and prolonged dissolution can be obtained when process conditions are adjusted within the reported values.

Keywords: Central composite design, Metoprolol succinate tablets, Ofada rice starch acetate, Response surface methodology