In Vitro Profiling of Gliclazide-Loaded Aerosil 380 Solid Dispersion–Based Tablets with Co-Processed Excipients

Abstract

Purpose

Gliclazide (GLC)-loaded Aerosil 380 solid dispersion (GA-SD)-based tablets with co-processed excipient composites were formulated to critically evaluate the physicochemical performance of the resulting tablets with enhanced drug release.

Methods

GA-SD was prepared using the solvent evaporation method with a 1:1 weight ratio based on a previously published report, and its drug release patterns were evaluated. Processed excipient composites, such as lactose-starch-povidone (LSP) and lactose-starch-povidone-sodium starch glycolate (LSPS), were prepared via a coprocessing strategy and evaluated for their ability to perform specific functions. At predetermined combination levels, aqueous dispersions of primary excipients were physically agglomerated at a controlled temperature below the gelatinization temperature (55 °C) before drying at 60 °C for 48 h. GA-SD and co-processed excipients (LSP and LSPS) were utilized to produce tablet batches GAC1 to GAC8 (Gliclazide-Aerosil 380–co-processed excipients, GAC) by direct compression. Through rigorous testing of tablet batches, the physicochemical properties of the resulting formulations were analyzed and compared to those of leading marketed formulations (MFs). FTIR studies were also conducted to detect drug-excipient interactions in the tablet formulations. The release mechanism of the GLC was determined by studying the dissolution process with various kinetic models. The GAC tablets were subjected to 40 °C/75% RH for 3 months to assess stability.

Results

All tablet formulations of GA-SD containing co-processed excipients met the weight, friability, disintegration time, mechanical strength, and homogeneity requirements. There was significantly more GLC released from the GAC formulations (p < 0.05) at each time point when the formulations were exposed to water than when the formulations were exposed to MFs. In vitro, testing revealed that the GAC5 to GAC8 formulations were the most efficient due to the presence of the superdisintegrant in the LSPS composite, which may be a contributing factor to the improvement in the dissolution rate by GA-SD. FTIR analysis revealed no notable chemical interactions between GLC and the excipients in the solid state. The Korsmeyer-Peppas model was the best-fit kinetic model, indicating that diffusion is the predominant mechanism of GLC dissolution. According to the commercial standards, the GAC tablets maintained an acceptable hardness, disintegration time, and drug content during the stability studies. Additionally, no significant changes in release profiles were observed in the selected batches (p < 0.05).

Conclusion

Compared with currently marketed formulations (MFs), GA-SD tablet formulations with co-processed excipients significantly improved the physicochemical properties, including the drug release rate. These findings could lead to the development of more effective and efficient tablet solid dosage forms of drugs with low water solubility, and co-processed excipients could be utilized as a more effective alternative to direct compression materials in tablet formulations.