02374nas a2200193 4500008004100000022001400041245007200055210006900127260000900196300001400205490000700219520174100226100002801967700002101995700001902016700001902035700002402054856010202078 2020 eng d a1528-748300aNaftopidil molecular salts with improved dissolution and permeation0 aNaftopidil molecular salts with improved dissolution and permeat cMAY  a3064-30760 v203 a

Naftopidil (NFPD) is a alpha 1 adrenoceptor antagonist drug. Low solubility and low permeability are the major drawbacks of this drug. The synthesis of multicomponent crystalline forms of this amine functional group drug with carboxylic acid coformers, both achiral and chiral acids, provides a solution to improve its solubility as well as permeability. Nine molecular salts were crystallized by liquid-assisted grinding followed by isothermal crystallization. Single-crystal X-ray diffraction analysis of the molecular salts showed that the structures are stabilized by strong N-H center dot center dot center dot O and O-H center dot center dot center dot O and weak C-H center dot center dot center dot O hydrogen bonds in the solid state. The bulk phase purity of new solid forms was confirmed by powder X-ray diffraction (PXRD), and the crystalline products were further characterized by IR spectroscopy and thermal analytical techniques (differential scanning calorimetry). The molecular salts exhibit superior dissolution rates compared to pure NFPD. However, during dissolution, NFPD showed decrease in concentration after 60 min for all salts due to precipitation. The supersaturation occurred due to salt disproportionation, which generates insoluble NFPD, as confirmed by PXRD of the residue. The salts reach high saturation concentration before 60 min, which is indicative of immediate release formulation to achieve fast onset of therapeutic activity. Moreover, the salts exhibit high saturation in phosphate buffer saline media and improved permeability compared to the pure drug. Finally, the D,L-malic acid racemate of NFPD shows enhanced dissolution and permeability compared to all other salts and pure NFPD.

1 aMannava, M., K. Chaitan1 aDandela, Rambabu1 aTothadi, Srinu1 aSolomon, Anand1 aNangia, Ashwini, K. uhttps://library.ncl.res.in/content/naftopidil-molecular-salts-improved-dissolution-and-permeation02110nas a2200205 4500008004100000022001400041245010300055210006900158260000900227300001200236490000700248520138000255100002801635700002201663700002201685700002401707700002401731700001901755856013001774 2021 eng d a1466-803300aEnhanced solubility, permeability, and tabletability of nicorandil by salt and cocrystal formation0 aEnhanced solubility permeability and tabletability of nicorandil cJAN  a227-2370 v233 a

Cocrystallization is a rational selection crystal engineering approach for the development of novel solid forms with enhanced physicochemical and mechanical properties. Nicorandil (NCR) is a niacinamide vitamin derivative used to treat angina pectoris. A binary solid form screen of NCR with homologous dicarboxylic acids afforded NCR-oxalic acid (NCR-OA, 1:1), NCR-fumaric acid (NCR-FA, 1:1), NCR-succinic acid (NCR-SA, 1:1), and NCR-suberic acid (NCR-SBA, 1:0.5). The binary solids were characterized by powder X-ray diffraction, IR and NMR spectroscopy, and DSC. NCR-FA and NCR-SBA were crystallized by slow evaporation from chloroform and toluene solvents, respectively. Single crystal X-ray diffraction confirmed that NCR-FA is a molecular salt, while NCR-SBA is a neutral cocrystal. NCR and the FA anion are connected via the robust carbovlate-pyridinium synthon, whereas in the NCR-SBA cocrystal, the components associate via the carboxylic acid- -pyridine synthon. The phase stability, solubility, dissolution rate, diffusion rate and tabletability studies have demonstrated that the binary solids exhibit improved physical and mechanical properties compared to the NCR drug. Specifically, the NCR-FA salt and NCR-SBA cocrystal have higher solubility, dissolution rate, and hardness at lower pressures, making the formulation suitable for tablet compression.

1 aMannava, M., K. Chaitan1 aGunnam, Anilkumar1 aLodagekar, Anurag1 aShastri, Nalini, R.1 aNangia, Ashwini, K.1 aSolomon, Anand uhttps://library.ncl.res.in/content/enhanced-solubility-permeability-and-tabletability-nicorandil-salt-and-cocrystal-formation01083nas a2200193 4500008004100000022001400041245011200055210006900167260000900236300001400245490000700259520038500266100002800651700002400679700002100703700001900724700002400743856012200767 2022 eng d a1359-734500aFluorobenzoic acid coformers to improve the solubility and permeability of the BCS class IV drug naftopidil0 aFluorobenzoic acid coformers to improve the solubility and perme cMAY  a5582-55850 v583 a

Crystalline salts of the low solubility and low permeability drug naftopidil were investigated with mono-, di-, tri-, and tetrafluorobenzoic acids as coformers to show that 245TFBA (2,4,5-trifluorobenzoic acid) is the optimal salt with faster dissolution and high permeability, thereby opening the study of fluorinated coformers in pharmaceutical cocrystals and salts.

1 aMannava, M., K. Chaitan1 aBommaka, Manish, K.1 aDandela, Rambabu1 aSolomon, Anand1 aNangia, Ashwini, K. uhttps://library.ncl.res.in/content/fluorobenzoic-acid-coformers-improve-solubility-and-permeability-bcs-class-iv-drug