Solution dynamics of 5‐fluorouracil entrapped in poly lactic‐co‐glycolic acid (PLGA) microsphere—A study with 1D selective NMR methods

Abstract

In this report, our main focus is to introduce a set of one‐dimensional (1D) NMR methods based on chemical shift, relaxation, and magnetization transfer, namely, NOE and chemical exchange involving selective pulse excitation to study the solution dynamics of drug in free and encapsulated state within polymeric microsphere. In this regard 5‐fluorouracil (5‐FU) loaded poly lactic‐co‐glycolic acid (PLGA) microspheres are prepared as model system via standard water‐in‐oil‐in‐water emulsification method. One‐dimensional 1H and 19F nuclear magnetic resonance (NMR) spectra of 5‐FU in presence of PLGA microspheres presented a significant change in linewidth and relaxation rates compared with free 5‐FU confirming encapsulation. Furthermore, loss of coupling pattern in 1H and 19F NMR of PLGA encapsulated 5‐FU as compared with free 5‐FU suggests an enhanced –NH and –H2O protons exchange dynamics in the interior of the microsphere indicating hydrated microsphere cavity. Quantification of exchange dynamics in case of free and PLGA‐encapsulated 5‐FU was attempted employing 1D selective NOESY and 1D multiply selective inversion recovery experiments. Analysis of the exchange rates confirmed existence of more than one kind of water population within the cavity as mentioned in an earlier solid state NMR report.

Influence of PLGA End Groups on the Release Profile of Dexamethasone from Ocular Implants

“…Furthermore, different forms of 1D solution NMR spectroscopy can be smartly used to unravel the dynamic water molecules within the solid PLGA formulation encapsulating drug crystals that are exposed to the dissolution environment. For example, Kumar and Pal utilized 1D selective NOESY and 1D multiple selective inversion recovery experiments to study the delicate dynamics of drug release, PLGA degradation, and local structure and dynamics of water inside the PLGA microsphere . Moreover, a major step forward to fast-track long-acting formulation development will be to develop a tool capable of predicting in vitro drug release as a function of rate of microstructure development, formulation design, API particle size, product dimensions, manufacturing parameters, and so forth.…”

“…Continuous quantitative analysis of PLGA and API release, LA/GA ratio, and GA and LA distribution is a challenge and can be resolved using the innovative flow NMR setup. Furthermore, different forms of 1D solution NMR spectroscopy can be smartly used to unravel the dynamic water 51 Moreover, a major step forward to fast-track long-acting formulation development will be to develop a tool capable of predicting in vitro drug release as a function of rate of microstructure development, formulation design, API particle size, product dimensions, manufacturing parameters, and so forth.…”