Micromeritic properties and instrumental analysis of physical mixtures and solid dispersions with adsorbent containing losartan: Comparison of dissolution-differentiating factors

Abstract

Micromeritic properties and instrumental analysis of physical mixtures (PM) and solid dispersions (SD) with colloidal silicon dioxides (Aerosils) as adsorbents containing losartan potassium (LST) were investigated to explain the dissolution-differentiating factors. LST was chosen as a poorly water-soluble drug in acidic low pH conditions. The SD of LST with an adsorbent (1:1) was prepared by the solvent evaporation method, while the PMs were prepared by simple grinding method in a mortar. The unexpected performance of PM over SD of poorly water-soluble drug (losartan) with adsorbent (colloidal silicon dioxide) by simple grinding method was obtained. The PMs rapidly increased the dissolution rate of LST up to 100% within 10min, performed in 900mL gastric buffer (pH1.2) at 37°C while the SD was dissolved slowly over 40min. To explain the unexpected increase of the dissolution rate of PMs, instrumental analysis and micromeritic properties were characterized. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) results showed that the SD gave an amorphous structure while the PM had crystalline form. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) images indicated that the PM had higher adsorption of drug onto the surface of the adsorbent than the SD. The PM showed significantly higher surface area due to high porosity than the SD, regardless of the larger particle size. The contact angle of PM was very low, suggesting significantly increased the wettability. Thus, an overall interpretation of the physicochemical difference of micromeritic powders, crystallinity and hydrogen bonding between PMs and SDs powders could be performed to explain the unexpected increase of LST dissolution. This report also showed that the SD was not always a good system to increase the dissolution rate of poorly water-soluble drug relative to PM.