NMR characterization of paclitaxel/poly (styrene-isobutylene-styrene) formulations

Abstract

TAXUS™ is a coronary drug-eluting stent system utilizing a formulation consisting of cellular-target drug paclitaxel and poly (styrene-isobutylene-styrene) (SIBS). The present study investigates the interaction and interfacial dynamics of paclitaxel incorporated in a nano-polymeric matrix system. Solution and solid-state CP/MAS NMR experiments were designed to characterize the microstructure of heterogeneous drug–polymer mixtures in terms of its composition, molecular mobility, molecular order, paclitaxel–SIBS molecular interactions, and molecular mobility of the drug in the polymer matrix. The NMR spectra demonstrated unchanged chemical shifts between the neat and incorporated paclitaxel, and suggested that the level of the interactions between paclitaxel and SIBS is limited to non-bonding interactions or physical interactions between paclitaxel and SIBS when mixed in solution under NMR detection. Carbon spin-lattice relaxation time and proton spin-lattice relaxation time in the rotating frame offer further confirmation that the mobility of paclitaxel is increased in the paclitaxel–SIBS mixture. The results also indicate that a change occurs from crystalline packing to amorphous packing in paclitaxel due to its intermolecular interaction with SIBS. Our studies were used in understanding the detailed structure, morphology, and molecular motion of paclitaxel in the paclitaxel–SIBS system and to probe chemical and physical heterogeneity down to the nanometer scale.