03011nas a2200277   4500008004100000022001400041245007900055210006900134260000800203300001200211490000800223520215300231653002002384653002202404653000802426653001602434653001502450100001802465700002602483700002202509700002202531700002302553700002002576700002402596856011302620       2018                        eng d  a0731-708500aRufinamide: crystal structure elucidation and solid state characterization0 aRufinamide crystal structure elucidation and solid state charact  cFEB  a185-1920 v1493 a<p>Rufinamide (R) is a triazole derivative approved for the management of partial seizures and seizures associated with Lennox-Gastaut Syndrome, in November 2007. Crystal structure, solid state characterization, drug-excipient compatibility and solubility play a pivotal role in formulation development. This work deals with the crystal structure elucidation of R by single crystal X-ray diffraction and solid state characterization by thermal, spectroscopic and crystallographic techniques. Drug- excipient compatibility was assessed by differential scanning calorimetry (DSC). New RP-HPLC method for quantification of R was developed with improved retention time. Solubility and dissolution of drug in different media was determined. Additionally, the flow behavior of the drug was evaluated by measuring Carr's index and Hausner's ratio, while the compressibility behavior was studied using Well's protocol. R crystallized from dimethylformamide (R-DMF) was utilized for single crystal analysis. The drug crystallized in triclinic crystal system with P-1 space group. Asymmetric unit cell consists of two molecules of R held by intermolecular hydrogen bond (connected by N-H center dot center dot center dot O, which forms the catemeric chain). Analytical outcomes from DSC, thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD) revealed that the drug was present in pure crystalline form and was devoid of any polymorphic or pseudopolymorphic impurities. Influence of pH on the solubility and dissolution of R-DMF was found to be insignificant. The drug exhibited poor aqueous solubility, which was improved nearly 4.6 fold with the addition of 2% sodium lauryl sulphate (SLS). The drug exhibits poor flow and elastic compression nature. Excipients such as poly ethylene glycol (PEG) 8000, SLS, lactose monohydrate, starch and Hydroxypropyl methylcellulose (HPMC) E15 were incompatible with R-DMF as identified by thermal analysis. It is envisaged that these information regarding solid state properties of R-DMF would aid in identifying a logical path for formulation development. (C) 2017 Elsevier B.V. All rights reserved.</p>10aCompressibility10aDissolution media10aDSC10aHPLC method10asolubility1 aSalunke, Nita1 aThipparaboina, Rajesh1 aChavan, Rahul, B.1 aLodagekar, Anurag1 aMittapalli, Sudhir1 aNangia, Ashwini1 aShastri, Nalini, R.  uhttps://library.ncl.res.in/content/rufinamide-crystal-structure-elucidation-and-solid-state-characterization