Biorelevant Dissolution Testing of Numerically Optimized Multiparticulate Drug Delivery Systems of Gliclazide

Gliclazide (GLZ) is an ampholyte with pH-dependent solubility in the gastrointestinal pH range. Although the effects of different pH values on GLZ release have been thoroughly investigated in compendial dissolution media, the effects of gastrointestinal fluid components and pH are not well known. Multiple response optimization was carried out employing two optimization criteria to obtain different release profiles (optimized alginate-gelatin beads, OP-1 and OP-2). Thermograms indicated polymorph formation (OP-1) and changes in GLZ crystallinity (OP-2). Fourier transform infrared (FT-IR)-spectra confirmed GLZ chemical stability. GLZ release in gradient compendial and biorelevant media was studied employing two dissolution methodologies using fed state simulated gastric and intestinal fluid (FeSSGF and FeSSIF, respectively). A validated HPLC/UV method for GLZ analysis in biorelevant media was developed. OP-1 and OP-2 showed low relative error between the actual and predicted values. In the gradient biorelevant media, OP-1 showed faster GLZ release than OP-2. In the gradient compendial media, OP-1 showed slower GLZ release in pH 1.2 and faster release in pH 7.4 than OP-2. Generally, both formulations showed slower GLZ release in biorelevant compared to compendial media. SEM images of OP-1 showed tiny pores on the bead surface after GLZ release in biorelevant media. Meanwhile, thin polymer layers were diffused around the beads (OP-1 and OP-2) after GLZ release in compendial media. In conclusion, GLZ release was mainly affected by pH rather than media components. A cost-effective biorelevant dissolution methodology was proposed. KEYWORDS: Gliclazide, biorelevant media, numerical optimization, gradient conditions, cost-effective methodology, dissolution