Influence of Pregelatinized Breadfruit Starch-Alginate Blend as a Sustained Release Polymer in Theophylline Microbeads Using Box Behnken Design

Abstract

Background: Apart from the coating property of modified starches on drugs, these natural polymers also acts as release rate retardants.
Objectives: To evaluate the potential of pregelatinized breadfruit (Artocarpus altilis) starch as a carrier in microbead formulations of theophylline using different blend combinations with sodium alginate and to determine the optimized formulation using Box-Behnken design.
Method: Theophylline microbeads were prepared using the ionic gelation method. The 3 factor-3 level Box-Behnken design was employed for constructing polynomial models to optimize the microbeads, involving 3 independent variables (polymer type, X₁, polymer: drug ratio, X₂, and concentration of calcium chloride, X₃) and 2 dependent variable (entrapment efficiency and quantity of drug released in 12 h, Q₁₂).
Results: Entrapment efficiency was 35 - 71 % while the values of Q12 was 38 - 88 %. The three variables, X₁, X₂ and X₃, were positive for entrapment efficiency but negative for Q₁₂, implying that increase from low to medium and then to high level resulted in an increase in entrapment but a decrease in Q₁₂ (sustained release), both desirable effects. Factor X1 had the most significant influence on entrapment efficiency and Q₁₂ (p = 0.002; p = 0.0001, respectively). The optimized formulation with starch:polymer 2:1, polymer:drug 3:1 and 7.5%w/v calcium chloride solution gave an entrapment efficiency 65% with Q₁₂ of 38.75%.
Conclusion: Pregelatinized breadfruit starch enhanced entrapment efficiency while retarding drug release, showing its potential as a polymer for sustained release in microbead formulations.

Keywords: Box-Behnken design; Breadfruit starch; Ionic gelation, Microbeads, Pregelatinization