Formulation, Optimization and Evaluation of Gastroretentive Alginate Beads of Ivacaftor by Using Factorial Design

Abstract

Aim: The main aim of study is to improve solubility of Ivacaftor by formulating into solid dispersions and to prolong the drug release, the solid dispersion of ivacaftor is formulated into gastroretentive alginate beads by Ionotropic Gelation method by using 24 factorial design. Methods: Ivacaftor solid dispersions were prepared by solvent evaporation method using polyethylene glycol, urea and mannitol as carriers by taking 1:1, 1:2 and 1:3 drug:carrier ratios. The best solid dispersion with better dissolution rate was incorporated into gastroretentive alginate beads by Ionotropic Gelation method using 24 factorial design. The independent variables are Sodium alginate concentration, Calcium chloride concentration, drug:HPMC ratio and drug:chitosan ratio and the dependent variables are percentage entrapment efficiency and percentage in-vitro drug release. The optimization of formulation was carried out using Stat Ease Design Expert Software. Results: The solid dispersion with polyethylene glycol and drug in 1:2 ratio showed better in-vitro dissolution of 98.17% at 120 mins. This solid dispersion was incorporated into gastroretentive alginate beads. The optimized formulation with 2% sodium alginate concentration, 4% calcium chloride concentration, 1:1 ratio of drug:HPMC and 1:1 ratio of drug:chitosan of solid dispersion entrapped alginate beads showed entrapment efficiency of 96.23% and in-vitro drug release of 95.62% at 12 hrs. The FTIR studies shown compatibility between drug and the excipients. The drug release kinetics of optimized formulation followed first order with Fickian diffusion. Conclusion: Ivacaftor entrapped solid dispersion entrapped alginate beads were successfully optimized using 24 full factorial design, which gave maximum entrapment efficiency and high drug release for extended period of 12 hrs. The release of ivacaftor was found to follow first order kinetics by Fickian diffusion. It can be concluded that this method may prove to be a suitable potential option for effective delivery of drug for treatment of cystic fibrosis.