Physicochemical reports of gliclazide-carplex solid dispersions and tablets prepared with directly compressible co-processed excipients.

OBJECTIVES: The main goal of this research was to develop better tablet formulations by utilizing solid dispersions (SDs) and coprocessing excipients composite to achieve a better release rate of poor water-soluble gliclazide.

METHODS: The solvent evaporation method made SDs of gliclazide with different carriers carplex 67, carplex 80, and carplex FPS 500 (weight ratio, 1:1). The drug release patterns of the SDs were all evaluated and optimized. The SDs were illustrated by using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Tablet batches FGC-1 to 8 were made using gliclazide-carplex 67 solid dispersions (GC67-SDs) and the co-processed composite of excipients, namely starch-MCC-povidone (SMP) and lactose-MCC-povidone-sodium starch glycolate (LMPS), prepared with coprocessing technology. We evaluated these batches by conducting physicochemical tests and comparing them to the existing commercial brand.

RESULTS: In a water medium, the release of gliclazide from SDs peaked within the first 30 min, showing a roughly 5∼6-fold increase compared to plain gliclazide. This quick dissolution rate may be due to the amorphization of the drug, which improved the specific surface area, and increased wettability caused by the hydrophilic properties of carplex particles. This has been confirmed through SEM, DSC, FTIR, and PXRD analysis. All FGC formulations had satisfactory pre-compression factor results, while the post-compression parameters indicated good mechanical strength and homogeneity across the blend. All produced tablets met the weight variation, friability, and disintegration time limit set by the compendia. Through in vitro drug release testing, it was discovered that all FGC tablet batches had consistent and nearly identical release results compared to SDs of gliclazide. However, the FGC-5 to 8 batches containing LMPS composites were determined to be the most effective formulations. In the first 30 min in a water medium, the percentage of drug generated from the FGC-8 tablets involving GC67-SDs and co-processed composite LMPS-4 is approximately 3.5 times higher than the average release of currently marketed products (MPs). After storing the selected FGC tablet batches for three months at 40 °C and 75 % RH, there were no noticeable alterations in the amount of drug and drug release profiles across the batches.

CONCLUSION: Based on these findings, it appears that using the carplex silica-based SDs approach, along with gliclazide and co-processing excipients composite, could result in significant benefits compared to the current commercial brands. This approach could be effectively utilized to create solid dosage forms for drugs that have low solubility in water.