Abstract
Famotidine (FMT) is an orally administered histamine H2-receptor blocker with limited bioavailability since it exhibits low solubility and low permeability. In addition, the recent withdrawal of ranitidine from the market, makes famotidine an interesting candidate to obtain solid forms with improved pharmacokinetic performance. In this work, crystal engineering concepts and the co-amorphous formation strategy were applied to obtain two novel solids. Crystalline famotidine malate (FMT-MT) and a vitreous phase (FMT-MTa) were prepared by solvent evaporation and mechanochemical synthesis, respectively. FMT-MT (monoclinic, S.G. P21/n) crystallizes with one FMT and one co-former molecules in the asymmetric unit forming a (R228) structural motif. FMT-MT resulted in a salt by proton transfer from one malic carboxylic group to the guanidine moiety of FMT. The three-dimensional packing is described as undulating layers of alternated FMT+ and MT- running along the a direction. FMT-MTa shows the inherent features of amorphous phases according to powder X-ray diffraction and DSC analysis. The higher physical stability was found for amorphous samples maintained at 4 °C up to 60 days. The solubility assays in water, indicate that FMT-MT and FMT-MTa are 2.02 and 2.68-fold more soluble than the marketed polymorph, whereas similar values were obtained in simulated gastric fluid.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
