Screening and RSM optimization for synthesis of a Gum tragacanth–acrylic acid based device for in situ controlled cetirizine dihydrochloride release

Abstract

The present research work was aimed at the development and optimization of a Gum tragacanth–acrylic acid based hydrogel for in situ release of cetirizine dihydrochloride under different pH conditions such as 2.0, 7.0 and 9.2 at 37 °C. Various process variables like solvent, temperature, pH, treatment time, initiator molar ratio, concentration of monomer and cross-linker were screened using a fractional factorial design approach. Using a half normality plot, the most significant parameters for maximizing swelling are found. These significant parameters (solvent, pH and monomer) are further optimized using center composite design. The ANOVA model predicted that the interaction between pH and monomer concentration had an antagonistic effect on percentage swelling. The sequential experimental design approach was able to optimize the reaction parameters for getting the candidate polymer with maximum swelling capacity, thereby maximizing water absorption capacity by fivefold. Characterization of the candidate hydrogel Gt-cl-poly(AA) was done using FTIR and SEM techniques. The candidate polymer with maximum water absorption capacity was found to exhibit maximum drug absorption which later on was released in a Case II diffusion manner at pH 2.0 and 7.0. However, a non-Fickian mechanism was exhibited at pH 9.2. The hydrogel has been found to show colon specific release behavior of the drug. The initial diffusion coefficient has a greater value than the later diffusion coefficient indicating a higher drug release rate during the early stage.