Very fast dissolving acid carboxymethylcellulose-rifampicin matrix: Development and solid-state characterization

L. C. LUCIANI-GIACOBBE; MARÍA V. RAMÍREZ-RIGO; Y. GARRO LINCK; G. A. MONTI; R. H. MANZO; M. E. OLIVERA

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2017 vol. 96 p. 398 - 410

0928-0987

One of the main obstacles to the successful treatment of tuberculosis is the poor and variable oral bioavailabilityof rifampicin (RIF),which is mainly due to its lowhydrophilicity and dissolution rate. The aimof thiswork was toobtain a hydrophilic newmaterial that allows a very fast dissolution rate of RIF and therefore is potentially usefulin the development of oral solid dosage forms.The acid form of carboxymethylcellulose (CMC) was co-processed with RIF by solvent impregnation to obtainCMC-RIF powder, which was characterized by polarized optical microscopy, powder x-ray diffraction, DSCTGA,hot stage microscopy, 13C and 15N solid-state NMR and FT-IR spectroscopy. In addition, the CMC-RIF matriceswere subjected to water uptake and dissolution studies to assess hydrophilicity and release kinetics.CMC-RIF is a crystalline solid dispersion. Solid-state characterization indicated that no ionic interaction occurredbetween the components, but RIF crystallized as a zwitterion over the surface ofCMC,which drastically increasedthe hydrophilicity of the solid. The CMC-RIF matrices significantly improved the water uptake of RIF anddisintegrated in a very short period immediately releasing RIF. As CMC improves the hydrophilicity and deliveryproperties of RIF, CMC-RIF is very useful in the design of oral solid dosage forms with very fast dissolution of RIF,either alone or in combination with other antitubercular drugs.