Caracterização estrutural de fármacos por RMN de sólidos e cálculos DFT: mefloquina e praziquantel

Abstract

Mefloquine hydrochloride (MQ) is a drug used in prophylaxis and treatment of malaria, an acute febrile infectious disease caused by protozoa of the genus Plasmodium. Due to side effects such as vomiting when administered to children, new formulations of this drug have been reported in the literature. One of these formulations, using polacrilin® resin, was analyzed by 13C CPMAS NMR to verify the nature of the resin-drug interaction. By comparing the constants associated with the cross-polarization dynamics for the carbons in isolated polacrilin and mefloquine hydrochloride with those in the resin-drug formulation, it was demonstrated that an interaction between the two materials occurred through complex formation, rather than merely being a physical mixture of the two main components. Praziquantel is a firstchoice drug for the treatment of schistosomiasis, used to treat entire populations in areas with poor sanitation due to its efficacy and lack of significant side effects. Using analytical instrumental techniques, such as Solid-State Nuclear Magnetic Resonance (NMR) and X-Ray Diffraction, and computational studies performed with the help of the Quantum ESPRESSO package, the crystalline structure of a polymorph of praziquantel present in commercial samples was investigated. Experimental conditions for acquiring 1H → 13C CPMAS NMR spectra were optimized, and in experiments with variation in contact time, the constants associated with crosspolarization dynamics, ă1Ā ÿ (hydrogen longitudinal relaxation time constant in the rotating reference frame) and ăÿÿ (cross-polarization time constant), were measured. With the GIPAW approach in Quantum ESPRESSO, the isotropic chemical shifts were computationally estimated from magnetic response parameter results. The computational results were compared to experimental results, and new assignments were proposed for the spectra of (RS)-Praziquantel.