Evaluating thermogravimetric analysis for the measurement of drug loading in mesoporous silica nanoparticles (MSNs)

Abstract

In this study, a thermogravimetric analysis (TGA) method for measuring the drug loading in mesoporous silica nanoparticles (MSNs) has been developed and evaluated in comparison with the drug loading quantification by high-performance liquid chromatography (HPLC). Indapamide was loaded into two different types of MSNs, namely Mobile Crystalline Material (MCM-41, pore size = 1.2 nm) and Santa Barbara Amorphous (SBA-15, pore size = 4.1 nm). Physical mixtures of the drug and silica gave a linear correlation between the observed and expected drug content for both TGA and HPLC, which were used for calibration purposes. The limit of detection (LOD) for the TGA method obtained from the physical mixture calibration curve was 0.77 % (w/w) and the r2 value was 0.9936, whereas the HPLC had a LOD of 0.06 % (w/w) and an r2 value of 0.9933. The sensitivity of the TGA method was well established using the drug loading studies, as it can detect the low loading of MCM-41 at 2.2 ± 0.21 % (w/w), compared to 5.1 ± 0.12 % (w/w) with the SBA-15. In all samples applied, the multiple comparison analysis showed an insignificant difference between the two methods (p > 0.05). The TGA data presented good evidence for using this technique as a sensitive, cost-effective, and low-variable quantitative analysis in the drug loading determination of the MSNs. TGA is not a selective method of quantification, but optimising the method using the pure and blank samples of MSNs and drug can significantly improve the sensitivity. This work provides a unique approach to apply TGA as a selective and more favourable method to characterise MSNs to do early formulation developments.