Application of Response Surface Methodology and Central Composite Design for the Optimization of Metformin Microsphere Formulation using Tangerine (Citrus tangerina) Pectin as Copolymer
Adenike Okunlola *
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
Olawunmi Lateefat Akindele
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
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.
Keywords: Central composite design, metformin microspheres, response surface methodology, tangerine pectin, entrapment, dissolution time.