Formulation and characterization of tramadol-loaded IPN microgels of alginate and gelatin: Optimization using response surface methodology

Tramadol-loaded interpenetrating polymer network (IPN) alginate-gelatin (AG) microgels (MG) were prepared by the chemical cross-linking technique with glutaraldehyde as cross-linking agent and were optimized using response surfaces. A central composite design for 2 factors, at 3 levels each, was employed to evaluate the effect of critical formulation variables, namely the amount of gelatin (X₁) and glutaraldehyde (X₂), on geometric mean diameter, encapsulation efficiency, diffusion coefficient (D), amount of mucin adsorbed per unit mass (Q_e) and 50 % drug release time (t₅₀). Microgels with average particle size in the range of 44.31-102.41 μm were obtained. Drug encapsulation up to 86.5 % was achieved. MGs were characterized by FT-IR spectroscopy to assess formation of the IPN structure and differential scanning calorimetry (DSC) was performed to understand the nature of drug dispersion after encapsulation into IPN microgels. Both equilibrium and dynamic swelling studies were performed in pH 7.4 phosphate buffer. Diffusion coefficients and exponents for water transport were determined using an empirical equation. The mucoadhesive properties of MGs were evaluated in aqueous solution by measuring the mucin adsorbed on MGs. Adsorption isotherms were constructed and fitted with Freundlich and Langmuir equations. In vitro release studies indicated the dependence of drug release on the extent of cross-linking and the amount of gelatin used in preparing IPNs. The release rates were fitted to a power law equation and Higuchi's model to compute the various drug transport parameters, n value ranged from 0.4055 to 0.5754, suggesting that release may vary from Fickian to quasi-Fickian depending upon variation in the formulation composition.