Very fast dissolving rifampicin (RIF)-carboxymethylcellulose (CMC) crystalline solid dispersion: solid state characterization

LUCIANI GIACOBBE LC; MANZO RH; MONTI, GA; GARRO LINCK, Y; OLIVERA ME

Ciudad Autónoma de Buenos Aires

Congreso; 76th FIP World Congress of Pharmacy and Pharmaceutical Sciences 2016; 2016

A crystalline solid dispersion obtained with carboximethylcellulose (CMC) and rifampicin (RIF), CMC-RIF, significantly improved the dissolution efficiency and the hydrophilicity of RIF, which are two of the critical factors that affects RIF bioavailability. The goal of this work was to characterize the crystalline form of RIF that interacts with CMC. RIF and CMC-RIF were subjected to powder XRD (p-XRD), FTIR and solid-state 13C and 15N CP/MAS, and short contact time (SCT, 200μs) 1H?15N NMR experiments. p-XRD patterns and the single resonance of a carbonyl at 196 ppm confirms that pure RIF is in the crystalline form I. A different p-XRD pattern was observed in CMC-RIF. Besides, the up and down-field shifts of the carbons assigned to the aromatic naphthalene group suggest deprotonation of the acidic OH phenolic group which is consistent with a zwiterionic form of RIF. The bathochromic shifts in the FTIR bands ascribed to the aromatic naphthalene group confirm such hypothesis. The 13C NMR spectrum of CMC-RIF presents narrowing in the signals when compared with the zwitterionic RIF.2H2O, used as reference, indicating a higher crystalline degree. In 15N NMR CMC-RIF presented chemical shifts which are larger than those of the zwitterionic form of RIF although in the same direction, suggesting interactions with CMC. A new signal at -338 ppm in SCT 1H-15N NMR confirmed the protonation of the RIF amine group in CMC-RIF. In conclusion, RIF interacts with CMC in its zwitterionic form which explains the hydrophilic character and the very fast dissolution rate of CMC-RIF.