Category: Formulation and Quality
Purpose: Syloids® are potential drug carriers because of their ability to stabilize the drug into an amorphous form. They are mesoporous silicas with an average pore size in 50 – 200 Å range. The drug loading into mesoporous silicas has often been low and the factors affecting the drug loading is poorly understood. The purpose of the present study was to determine the drug loading efficiency of three grades of Syloids® possessing different pore size and particle size, but similar pore volume.
Methods: Three grades of Syloid®, namely Syloid® 3150, Syloid® 3050 and Syloid® 244 FP possessing particle size of 150 µm, 50 µm, and 3.5 µm and average pore volume of 1.70 cm3/g, 1.69 cm3/g and 1.60 cm3/g, respectively, were used. Indomethacin, which is a poorly water-soluble, crystalline drug was used as a model drug. The drug was loaded into Syloid® using solvent impregnation method. The drug solutions containing three concentrations of indomethacin, i.e. 100 mg/ml, 300 mg/ml and 500 mg/ml, were prepared by dissolving indomethacin into dimethyl sulfoxide (DMSO). The Syloids®, in the ratio of 160 mg of Syloid® for 1 mL of drug solution, were then immersed in the drug solution for 1 hr with continuous stirring. The drug solution containing Syloid® were vacuum filtered, and the loaded Syloids® were dried for 24 hrs at 70°C. Any remaining amount of moisture or residual solvent was removed by storing the loaded Syloid® samples in a desiccator maintaining 10% RH at room temperature for 24 hrs. Differential scanning calorimetry (DSC) was performed to determine possible crystallization of indomethacin on the surface or inside the pores of Syloid®. The amount of indomethacin loaded into Syloid® was determined using helium pycnometer and ultraviolet spectroscopy. Helium pycnometer was used to determine the drug loading by determining the difference between the true density of the drug-loaded and plain Syloid® using the relationship, q = 𝜌𝑃𝑆𝑖− 𝜌𝑠𝑎𝑚𝑝𝑙𝑒/𝜌𝑃𝑆𝑖− 𝜌𝑑𝑟𝑢𝑔, where q is the amount of drug loading, 𝜌PSi, 𝜌sample, and 𝜌drug are the true densities of the plain silica, the drug-loaded silica, and the drug, respectively. The drug payload was also determined by UV spectroscopy at a wavelength of maximum absorbance at 318 nm.
Results: The DSC analysis demonstrated broad endotherms around the melting point of indomethacin (160°C) in the case of all the drug-loaded Syloid® samples which indicate incomplete recrystallization of the drug. This was due to the mesoporous nature of Syloid® that physically confines the drug molecules from undergoing re-crystallization and forming long-range crystals. The true density of Syloid® was found to decrease after the drug loading, indicating that the drug was present inside the pores. The presence of drug in amorphous clusters along with some individual molecules decreases the true density of silica. The payload calculated by the pycnometer was found to be 56.1-79.4% w/w, 58.0-86.6% w/w and 56.4- 92.0% w/w for Syloid® 3150, Syloid® 3050 and Syloid® 244 FP, respectively. However, the drug loading determined from UV spectrophotometric analysis was found to be in the rage of 17.2- 45.0% w/w, 7.0-66.0% w/w, and 26.9-38.7% w/w for Syloid® 3150, Syloid® 3050 and Syloid® 244FP, respectively. This showed that the drug was present in the superficial pores of Syloid® which blocked the flow of helium gas during the determination of true density resulting in the overestimation of drug loading. The concentration of drug solution was found to have a significant effect on drug loading in the case of Syloid® 3050 where an increase in drug concentration in the solution was found to increase the drug loading. However, in the case of Syloid® 3150 and Syloid® 244FP, the drug loading was found to increase when the drug concentration increased from 100 mg/ml to 300 mg/ml and remained constant when the concentration was increased to 500 mg/ml. This was possibly due to the saturation of pores of Syloid® with drug molecules resulting in the saturation of drug loading. Also, the results demonstrated the significance of particle size of Syloid® in drug loading where large particle size Syloid® 3150 and smaller particle size Syloid® 244FP exhibited lower drug loading, whereas medium particle size Syloid® 3050 showed higher drug loading.
Conclusion: Syloids® are excellent drug delivery carriers; however, the mechanism of drug loading in Syloids® is poorly understood. The study results add a piece of knowledge to the existing information and demonstrate the significance of particle size of silica and the concentration of the drug solution on the drug loading in Syloid®.