Application of Response Surface Methodology and Central Composite Design for the Optimization of Metformin Microsphere Formulation using Tangerine (Citrus tangerina) Pectin as Copolymer

Aims: To prepare metformin microspheres by ionic gelation using novel pectin from the peel of tangerine, Citrus tangerina (Rutaceae), as a copolymer with sodium alginate.

Study Design: Central composite design and response surface methodology.

Place and Duration of Study: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria, between September 2015 and February 2016.

Methodology: Central composite design and response surface methodology were applied to evaluate the interactive effects of three variables: Percent of pectin in polymer blend, X1, (50 to 75% w/w), curing time, X2, (10 to 30 min) and concentration of chelating agent (calcium chloride), X3, (5 to 10% w/v) on entrapment and dissolution time (t90).

Results: Entrapment efficiency was 59.10 to 94.90% and t90 was 6.52 to 10.50 h. X1 and X3 had significant effects on entrapment and t90 (p < 0.0001). The interactions between X2 and X3 was significant at p = 0.033 for entrapment. The correlation coefficients (R2 = 0.9557 and R2(Adj) = 0.9158 for entrapment; R2 = 0.9677 and R2 (Adj) = 0.9387 for t90) showed that the regression model represented the experimental data well. The optimization of the analyzed responses demonstrated that peak conditions for obtaining desired maximum responses, entrapment (102.66%) and t90 (12.27 h), were 82.91% w/w pectin; 36.33 min curing time and 7.50% w/w of calcium chloride.

Conclusion: Tangerine pectin could serve as a cheaper alternative polymer for the formulation of microspheres.