01834nas a2200193 4500008004100000022001400041245013200055210006900187260000900256300001400265490000700279520110900286100002401395700002501419700002501444700002001469700002401489856012701513 2020 eng d a1466-803300aDrug-drug cocrystals of anticancer drugs erlotinib-furosemide and gefitinib-mefenamic acid for alternative multi-drug treatment0 aDrugdrug cocrystals of anticancer drugs erlotinibfurosemide and  cOCT  a6137-61510 v223 a

Drug-drug cocrystals of anticancer drugs erlotinib and gefitinib with furosemide and mefenamic acid, respectively, have been synthesized. The 1:1 erlotinib-furosemide cocrystal crystallizes in the monoclinic centrosymmetric P2(1)/n space group containing one molecule of each component in the asymmetric unit. In contrast the 1:1 gefitinib-mefenamic acid cocrystal hydrate belongs to the monoclinic centrosymmetric P2(1)/c space group comprising one molecule of both drugs along with one water molecule in the asymmetric unit. The solubility and dissolution rate study revealed higher solubility for BCS class II drugs, furosemide, and mefenamic acid, while the solubility and dissolution rate of erlotinib showed a significant reduction in the cocrystal salt. Conversely, the solubility of gefitinib didn't reveal a substantial decrease; however, the dissolution rate has been reduced in the cocrystal hydrate. Further, an attempt has been made to correlate the crystal structures of the erlotinib-furosemide and gefitinib-mefenamic acid cocrystals with their solubilities and dissolution rate.

1 aGeorge, Christy, P.1 aThorat, Shridhar, H.1 aShaligram, Parth, S.1 aSuresha, P., R.1 aGonnade, Rajesh, G. uhttps://library.ncl.res.in/content/drug-drug-cocrystals-anticancer-drugs-erlotinib-furosemide-and-gefitinib-mefenamic-acid03089nas a2200181 4500008004100000245013200041210006900173260000800242300001400250490000700264520238600271100002502657700002402682700002502706700002002731700002402751856013202775 2021 eng d00aPolymorphs and hydrates of the anticancer drug erlotinib: X-ray crystallography, phase transition and biopharmaceutical studies0 aPolymorphs and hydrates of the anticancer drug erlotinib Xray cr cJUN a3961-39740 v233 a

Erlotinib, a non-small cell lung cancer BCS class II drug, was found to occur as two polymorphs and two hydrates depending on the crystallization conditions. The monohydrate (form III), which has been reported in patents and publications, is the preferred crystalline phase from solution crystallization. The other forms (polymorphs, forms I and II, and a trihydrate, form IV) are solvent and condition-specific. Form I was exclusively and reproducibly obtained from dried non-polar solvents (viz. toluene, benzene, and xylene) using a solution crystallization method under controlled conditions. In contrast, form II was obtained by the rotary evaporation technique under reduced pressure from polar solvents (viz. dichloromethane, ethyl acetate, acetone, and acetonitrile). Slow evaporation from polar and non-polar solvents under open conditions yielded form III crystals, whereas evaporation from acetone-acetonitrile-water mixtures yielded form IV crystals. DSC and variable temperature PXRD studies revealed form I to be the most stable phase while the other solid forms displayed thermally induced polymorphic transitions into form I crystals. Further, form I and form III are found to be stable over the 30-90% RH range. Further, form I displayed solution-mediated transformation into form III (monohydrate) when left to stand in the mother liquor for a longer duration (1-2 days). Similarly, the unstable form IV crystals transformed into the stable form III crystals within 1-2 h when exposed to an open atmosphere. Fast crystallization from polar solvents using the rotary evaporation technique enabled us to capture the metastable polymorph, form II. Early separation of form I from its mother liquor prevented its solution-mediated transformation into the monohydrate, form III. The water activity study revealed that form III is the most preferred solid phase in the presence of water. Dissolution rate measurements showed that the rate of form II is almost comparable to that of the marketed erlotinib hydrochloride. In contrast, for the other forms, the dissolution profiles showed a considerable decrease. Although the crystal structures of form I and form III have been published previously, this manuscript gives a comprehensive overview of the free base solid forms of erlotinib, the phase transitions amongst them and their biopharmaceutical properties.

1 aThorat, Shridhar, H.1 aGeorge, Christy, P.1 aShaligram, Parth, S.1 aSuresha, P., R.1 aGonnade, Rajesh, G. uhttps://library.ncl.res.in/content/polymorphs-and-hydrates-anticancer-drug-erlotinib-x-ray-crystallography-phase-transition-and02779nas a2200217 4500008004100000245010100041210006900142260000900211300001400220490000700234520201600241100002502257700002402282700002102306700002702327700001902354700001702373700001802390700002402408856012902432 2023 eng d00aRivaroxaban eutectics with improved solubility, dissolution rates, bioavailability and stability0 aRivaroxaban eutectics with improved solubility dissolution rates cJUN  a3253-32630 v253 a

Rivaroxaban (RXB) is a direct factor Xa inhibitor used for the treatment of deep vein thrombosis (DVT, a blood clot in the leg) and pulmonary embolism (PE, a blood clot in the lung) and to prevent blood clots in atrial fibrillation following hip or knee surgery. However, RXB suffers from poor solubility that hinders its broader application. Although its cocrystals are reported for solubility enhancement, the methodology used to prepare multi-component crystals is complex. Also, it uses hazardous solvents to develop cocrystals. We have prepared eutectics of RXB with caffeic acid (CAA), coumaric acid (CA), fumaric acid (FA), succinic acid (SA), mandelic acid (MA) and trimesic acid (TA) and analyzed them using hot stage microscopy (HSM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier transform infrared spectroscopy (FTIR) techniques. The saturation solubility and dissolution rate profiles were also obtained to investigate the effect of eutectics on these parameters. Amongst all the coformers tested, coformers CAA, CA, and FA showed significant enhancement in the solubility of RXB. The powder dissolution rate of the eutectics showed considerable enhancement compared to that of RXB. In vivo pharmacokinetic study was carried out for RXB-CAA, RXB-CA and RXB-FA in rats and compared with RXB, which showed 1.5 and 1.4 times enhancement in relative bioavailability for RXB-CAA and RXB-CA, respectively. Stability studies were carried out as per ICH guidelines for all the eutectics, which revealed excellent stability over six months under accelerated (40 degrees C and 75%) conditions and twelve months under long-term (30 degrees C and 60% RH) conditions. The DFT studies carried out using the B3LYP/TZVP level of theory revealed higher Gibbs free interaction energy (Delta G(int)) for homosynthons (drugMIDLINE HORIZONTAL ELLIPSISdrug and coformerMIDLINE HORIZONTAL ELLIPSIScoformer) than heterosynthons (drugMIDLINE HORIZONTAL ELLIPSIScoformer).

1 aShaligram, Parth, S.1 aGeorge, Christy, P.1 aSharma, Himanshu1 aMahadik, Kakasaheb, R.1 aPatil, Sharvil1 aVanka, Kumar1 aArulmozhi, S.1 aGonnade, Rajesh, G. uhttps://library.ncl.res.in/content/rivaroxaban-eutectics-improved-solubility-dissolution-rates-bioavailability-and-stability01312nas a2200241 4500008004100000022001400041245008900055210006900144260000900213300001400222490000700236520051800243653000600761653002700767653001800794653002100812100002800833700001700861700002500878700002100903700002400924856012200948 2024 eng d a1359-734500aElectrochemically enabled (3+2) cycloaddition of unbiased alkenes and β-dicarbonyls0 aElectrochemically enabled 32 cycloaddition of unbiased alkenes a cMAY  a5836-58390 v603 a

A (3+2) cycloaddition between unbiased alkenes and 1,3-dicarbonyls is accomplished by judicious choice of electrode material and electrocatalyst to access dihydrofuran derivatives. A fluorinated porous carbon electrode with appropriate thickness governs unprecedented reactivity. This methodology eliminates the necessity for any stabilizing group within the alkene substrate. This is a rare example of the annulation of unbiased internal and terminal alkenes with cyclic and acyclic beta-dicarbonyls.

10a110a3-DICARBONYL COMPOUNDS10aDIHYDROFURANS10aFACILE SYNTHESIS1 aSuryawanshi, Sharad, M.1 aSahoo, Suman1 aShaligram, Parth, S.1 aManna, Narugopal1 aSamanta, Ramesh, C. uhttps://library.ncl.res.in/content/electrochemically-enabled-32-cycloaddition-unbiased-alkenes-and-%CE%B2-dicarbonyls00975nas a2200277 4500008004100000022001400041245013800055210006900193260000800262490000600270653000800276653001500284653001800299653001900317100003000336700002300366700002500389700001900414700002500433700002400458700002100482700001800503700002000521700002400541856013200565 2024 eng d a2365-654900aPyridazine-Based Aggregation Induced Emission Active Conjugates: Synthesis, Single Crystal XRD Analysis, and Self-Assembly Assessment0 aPyridazineBased Aggregation Induced Emission Active Conjugates S cOCT0 v910aAIE10aPyridazine10aSelf-assembly10aSingle crystal1 aWaghchoure, Aishwarya, P.1 aSangale, Vijay, B.1 aShaligram, Parth, S.1 aLambud, Sushil1 aPardeshi, Satish, K.1 aGonnade, Rajesh, G.1 aBandaru, Sateesh1 aMore, Sandeep1 aReddy, Prakasha1 aBhosale, Rajesh, S. uhttps://library.ncl.res.in/content/pyridazine-based-aggregation-induced-emission-active-conjugates-synthesis-single-crystal-xrd01272nas a2200181 4500008004100000022001400041245007600055210006900131260000900200300001400209490000700223520066100230100002700891700002500918700002000943700002300963856010400986 2024 eng d a1463-907600aSolid-state NMR method for characterization of pharmaceutical eutectics0 aSolidstate NMR method for characterization of pharmaceutical eut cJAN  a3800-38030 v263 a

Pharmaceutical eutectics are extremely useful for designing formulations, and currently, there are no techniques other than differential scanning calorimetry (DSC) that can confirm their formation. In this study, we demonstrate that 1H fast magic angle spinning (MAS) solid-state NMR (SSNMR) experiments can confirm the formation of eutectics by detecting their intermolecular hydrogen bonding interactions. 2D 1H-1H double quantum single quantum (DQSQ) correlation SSNMR experiment is demonstrated which can confirm the formation of pharmaceutical eutectics for which there are no techniques other than differential scanning calorimetry (DSC).

1 aHareendran, Chaithanya1 aShaligram, Parth, S.1 aGonnade, Rajesh1 aAjithkumar, T., G. uhttps://library.ncl.res.in/content/solid-state-nmr-method-characterization-pharmaceutical-eutectics