Increment of the dissolution efficiency of poor water-soluble drugs comparing different loading methods in mesoporous materials

GALLO LOREANA; BUCALÁ VERÓNICA; BOIX ALICIA; PEDERNERA MARISA; TISCORNIA INÉS; ADROVER ESPERANZA

Congreso; WCCE11 - 11th World Congress of Chemical Engineering; 2023

For oral drug administration, the dissolution step represents the limiting stage for the absorption of a drug in the gastrointestinal tract. However, more than 70% of the existing drugs are poorly water-soluble compounds limiting their oral formulation [1]. An interesting strategy to improve the solubility/dissolution rate of these drugs is loading them into carriers with a large surface area, such as mesoporous silica particles because their crystalline structure changes to a more soluble amorphous one. SBA-15 is a promising material to this end. Even though, there are different loading methods such as immersion, impregnation and incipient wetness impregnation, the immersion method offers important advantages such as simplicity and reproducibility. In this work, SBA-15 was synthesized and loaded with albendazole (ABZ, antiparasitic drug). Drug loading was performed at two different ABZ:SBA-15 ratios by immersion and a modified immersion method. SBA-15 materials were synthesized according to different procedures in order to obtain rods and fibers. Subsequently, the mesoporous materials were loaded with ABZ by: i) immersion method which implied dissolving ABZ in acetic acid and then, incorporating SBA-15 and, ii) a modified immersion method which consists on sonicating the solution for an hour previous immersion. Both procedure were repeated for two different ABZ:SBA-15 ratio (6:1, 1:1). The amount of ABZ loaded was determined by elemental analysis. The dissolution rate of ABZ was evaluated in a type II dissolution apparatus (900 ml of 0.1 N HCl, 37 °C and 100 rpm of stirring). The ABZ concentration was measured with a UV-visible. The dissolution efficiency (DE) was estimated by means of the DDSolver software. Table 1 shows the effect of the different loading methods, SBA-15 morphologies and ABZ:SBA-15 ratios on drug loading (DL) as well as on the DE. It is possible to observe that the highest load was obtained by immersion for rods at the maximum ABZ:SBA15 ratio. On the other hand, the lowest load was obtained by immersion for fibers at the minimum ABZ:SBA-15 ratio. Interestingly, the maximum DE was obtained for the lowest DL. Fibers present higher DE values. The effect of sonicating the sample before immersion shows different effects on DL depending on ABZ:SBA-15 ratio. For ABZ:SBA-15 ratio 6:1, sonication reduces the DL. Instead sonication increases DL for ABZ:SBA-15 ratio equals to 1:1. Taking into account that the DE of pure ABZ is 29.5%, it is important to highlight that all the samples (A-I) present higher DE than the crystalline drug. In conclusion, the SBA-15 morphology and ABZ:SBA-15 ratio are relevant parameters in the formulation of the oral pharmaceutical dosage form.References1. Zhang, X., Xing, H., Zhao, Y., Ma, Z. (2018). Pharmaceutical dispersion techniques for dissolution and bioavailability enhancement of poorly water-soluble drugs. Pharmaceutics, 10(3), 74.