Direct and Real-Time Quantification Of Bortezomib Release From Alginate Microparticles Using Boron (¹¹B) Nuclear Magnetic Resonance Spectroscopy

Abstract

This study developed and validated a solution-state quantitative boron nuclear magnetic resonance ( 11 B qNMR) method for the real-time quantification of boron containing bioactive agents with emerging therapeutic applications. Hence, this study may offer an alternative analytic method to estimate drug potency, purity, stability, or in vitro release kinetics of boron-containing pharmaceutical formulations/compounds, especially in cases where dialysis is typically required but limited. The 11 B qNMR method was linear in the range tested, and the detection and quantification limits were 1.87 and 5.65 mM, respectively. The method was also specific, accurate, precise, and robust (%RSE < 2%). The 11 B qNMR method was applied to the in vitro release study of a model drug, bortezomib (BTZ), from alginate microparticles, and results were compared to the traditional dialysis method. The alginate microparticles were prepared by spray drying, and the mean particle diameter was 2.36 ± 0.19 μm with a polydispersity index (PDI) of 0.253. The microparticles surface charge density was −57.1 ± 2.2 mV. More than 20% difference in the total amount of BTZ released from the microparticle formulation was observed between the direct 11 B qNMR and dialysis methods. Furthermore, the dialysis method was not suitable to determine the initial burst release of BTZ from the microparticles. Throughout the release study, the dialysis method consistently underestimated the level of drug released, probably due to the separating membrane that can interfere with the real-time drug transport process. Overall, compared to the dialysis method, the direct 11 B qNMR method was accurate and provided a direct and real-time quantification of BTZ for an effective study of drug release kinetics.

In-cell NMR: Why and how?

“…Other more exotic species have been studied sporadically by NMR in cells, e.g. 10 B/ 11 B or 195 Pt [146][147][148][149][150][151][152]. Overall, NMR has been very useful in understanding the dynamics of all these ions in cells.…”

Research Progress of NMR in Natural Product Quantification

“…These new, advanced methods could minimize the effects of impurities and improve the applicability of previous methods. Coulibaly et al [ 147 ] developed a qNMR method for real-time quantification, providing convenience for the real-time monitoring of contents. Golowicz et al [ 107 ] presented a novel approach named swept coherence transfer (SCoT), which is based on the idea of time-resolved NUS acquisition in HSQC experiments; the coherence transfer delay is co-incremented with non-uniformly sampled evolution time.…”