02918nas a2200241 4500008004100000022001400041245013300055210006900188260000900257300001100266490000900277520208400286653001802370653002202388653001502410653001302425100002102438700002002459700002402479700002802503700002102531856012402552 2023 eng d a0022-286000aExploration of different solid variants of the anticancer medication Panobinostat (PNB) with improved physicochemical attributes0 aExploration of different solid variants of the anticancer medica cNOV  a1360860 v12923 a

Panobinostat (PNB), is a medication used for the treatment of multiple myeloma. It is a BCS Class II drug with strong permeability and poor solubility. Therefore, it is highly desirable to investigate novel PNB variants with improved physiochemical properties. In this regard, several solid forms of PNB have been produced employing mechanochemistry and solution crystallisation techniques using a variety of GRAS (Generally Recognized as Safe) salt formers, notably oxalic acid (OA), fumaric acid (FA), maleic acid (MA), and succinic acid (SA). Powder X-Ray Diffraction (PXRD), Single Crystal X-Ray Diffraction (SCXRD), and thermal analysis such as Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC) were used to characterize all the synthesised molecular adducts. Hirshfeld surfaces and fingerprint plots demonstrate that the molecular entities are stabilized by O & BULL;& BULL;& BULL;H, C & BULL;& BULL;& BULL;H, C & BULL;& BULL;& BULL;C and H & BULL;& BULL;& BULL;H intermolecular interactions. Moreover, the solubility of parent PNB and its molecular adducts in pH 1.2/pH 6.8 was evaluated at room temperature. In every instance, an increase in the solubility of molecular salts relative to the parent medication is seen, notably PNB.MA exhibits enhanced solubility of 0.294 mg/ml, a 73fold increase over the parent PNB. Furthermore, it is observed that this upsurge in solubility of all the forms is static at pH 1.2. A thorough analysis of the recovered residue after solubility showed that most of the molecular adducts were stable at pH 6.8 and did not display any phase change or dissociation (with the exception of PNB.MA), but at pH 1.2 they transferred into a new stable form and extensive analysis confirmed that it converted into PNB.Cl salt. To the best of our knowledge, this is the first report on novel solid forms of PNB with enhanced physicochemical properties which implies that the obtained PNB molecular adduct may help in the development of improved PNB formulations.

10aHydrogen bond10aMolecular adducts10asolubility10aSolvates1 aKenguva, Gowtham1 aGiri, Lopamudra1 aRout, Smruti, Rekha1 aAcharya, Achyuta, Nanda1 aDandela, Rambabu uhttps://library.ncl.res.in/content/exploration-different-solid-variants-anticancer-medication-panobinostat-pnb-improved02163nas a2200205 4500008004100000245011100041210006900152260000800221300001200229490000700241520142900248100002101677700002401698700002301722700002001745700001901765700002001784700002101804856013201825 2024 eng d00aExploring novel cocrystals of milrinone: a cardioprotective drug combined with nutraceuticals and an NSAID0 aExploring novel cocrystals of milrinone a cardioprotective drug  cDEC a138-1450 v273 a

Milrinone is a bipyridine phosphodiesterase (PDE) inhibitor of the second generation. It's a PDE-III antagonist that raises cAMP levels to support heart function and acts as a systemic vasodilator in chronic decongested cardiovascular illness. It is categorised as class II in the Biopharmaceutics Classification System (BCS), indicating that it exhibits poor aqueous solubility and high permeability. Three new cocrystals of the cardioprotective drug milrinone (MR) with two nutraceuticals, e.g. sesamol (SES) and resveratrol (RES), and an anti-inflammatory drug, e.g. niflumic acid (NIF), were successfully synthesised using mechanochemical and solution crystallisation techniques. Thermal analysis (DSC and TGA) and diffraction tools (PXRD and SCXRD) were used to obtain structural insights into all the cocrystals. Their crystal structures indicate that the dimeric interactions in MR are preserved in the crystal structures in addition to carboxylic acid/phenol & ctdot;pyridine heterosynthons. Among the three synthesized molecular solids, MR.SES was more soluble than the native drug. The solubility of the cocrystals was correlated with polar surface contacts, the solubility of the coformer and melting points (inversely). We believe that the new MR.SES cocrystal offers a novel approach to enhance the drug's solubility, which may have a positive impact on its synergistic cardioprotective effects.

1 aKenguva, Gowtham1 aRout, Smruti, Rekha1 aShaikh, Tabrez, R.1 aBaidya, Debjani1 aShelke, Nikita1 aSanphui, Palash1 aDandela, Rambabu uhttps://library.ncl.res.in/content/exploring-novel-cocrystals-milrinone-cardioprotective-drug-combined-nutraceuticals-and-nsaid02444nas a2200289 4500008004100000022001400041245014900055210006900204260000800273300001500281490000600296520142700302653002001729653002901749653001801778653004201796653001701838100002101855700002401876700001601900700002001916700002301936700002201959700002201981700002102003856013002024 2024 eng d a2365-654900aNew binary adducts of panobinostat with different carboxylic acid based NSAIDs: structural analysis and physicochemical properties investigation0 aNew binary adducts of panobinostat with different carboxylic aci cNOV ae2024035390 v93 a

Adoption of multitarget, cost-effective fixed-dose medication combinations can help lower the pill load without increasing the risk of adverse events. In this study, three new 1:1 drug-drug binary solid forms of panobinostat (PNB) and nonsteroidal anti-inflammatory drugs (NSAIDs) were effectively synthesized by liquid-assisted grinding and slow evaporation crystallization techniques. The obtained solid forms were extensively characterized by various analytical techniques. The structural investigation revealed that all molecular adducts formed salt with a comparable R42\${\textbackslashmathrm{R}}_4<\^>2\$(10) graph set pattern created by heteromeric interactions formed between PNB and corresponding salt formers. To determine the dissolving behavior of the newly developed adducts, solubility tests were performed at various pH levels (pH 1.2 and pH 7), and the results indicated that the solubility of all forms is increased at pH 7.0, particularly PNB.NIF has a solubility of 0.195 mg/mL, which is seven times higher than the parent drug. Furthermore, PXRD was used to assess the stability of the synthesized adduct at varied temperature and humidity levels and it was found that all the adducts are stable. Based on the findings, we hope that the newly found PNB drug-drug binary adducts have possible potential to broaden the use of drug combinations without changing the chemical structures.

10aDrug-drug salts10aHeteromeric interactions10aHydrogen bond10aNon-steroidal anti-inflammatory drugs10aPanobinostat1 aKenguva, Gowtham1 aRout, Smruti, Rekha1 aKar, Ananya1 aGiri, Lopamudra1 aShaikh, Tabrez, R.1 aJadab, Madhusmita1 aPal, Satyanarayan1 aDandela, Rambabu uhttps://library.ncl.res.in/content/new-binary-adducts-panobinostat-different-carboxylic-acid-based-nsaids-structural-analysis00844nas a2200241 4500008004100000245010300041210006900144260000900213300001400222490000700236653002900243653001400272653002500286653001500311100002100326700002400347700002300371700002000394700001900414700002000433700002100453856012800474 2024 eng d00aStructural insights into ketanserin salts with aliphatic acids and their physiochemical properties0 aStructural insights into ketanserin salts with aliphatic acids a cNOV  a6260-62680 v2610aPHARMACEUTICAL COCRYSTAL10aSEROTONIN10aSHYDROCHLOROTHIAZIDE10asolubility1 aKenguva, Gowtham1 aRout, Smruti, Rekha1 aShaikh, Tabrez, R.1 aBaidya, Debjani1 aShelke, Nikita1 aSanphui, Palash1 aDandela, Rambabu uhttps://library.ncl.res.in/content/structural-insights-ketanserin-salts-aliphatic-acids-and-their-physiochemical-properties02497nas a2200289 4500008004100000022001400041245014200055210006900197260000800266300001100274490000900285520150000294653002401794653001801818653003501836653001501871100002101886700002401907700001601931700002001947700002801967700002301995700002002018700001902038700002102057856012902078 2025 eng d a0022-286000aSynthesis, characterization and theoretical investigations of the newly developed molecular salts of an anti-psychotic drug (Penfluridol)0 aSynthesis characterization and theoretical investigations of the cAPR a1413920 v13283 a

Penfluridol (PEN) is a clinically relevant antipsychotic medication used to treat schizophrenia; nevertheless, its bioavailability is limited due to its poor solubility. To address this issues, new molecular salts of PEN are being produced utilizing an array of GRAS (Generally Recognised AS Safe) salt formers such as oxalic acid (OXA), malonic acid (MAL), maleic acid (MAE), and an artificial sweetener (saccharin (SAC)). A variety of solid-state analytical techniques were used to identify and characterize the resulting molecular salts. Moreover, PEN and its novel salts' solubility were assessed using high-performance liquid chromatography (HPLC) and the data revealed that among all the adducts PEN.MAL exhibited a significantly higher solubility which is similar to 15 times more than the parent drug PEN. Furthermore, in order to enhance comprehension of the hydrogen bonding interaction, the Hirshfeld surface (HS), frontier molecular orbital (HOMO-LUMO), non-covalent interaction plots (NCIs), and electrostatic potential maps (ESP) investigations are discussed. Additionally, the stability of the synthesized adducts was evaluated over a 2-week period under accelerated humidity (90 % +/- 5 % RH, 40 +/- 1 degrees C) and it was observed that all the adducts demonstrated excellent stability. In light of the aforementioned observations, we expect that the latest discovery will be a superior alternative for refining and strengthening the pharmacological features of PEN.

10aAnti-psychotic drug10aHydrogen bond10aLiquid-assisted grinding (LAG)10asolubility1 aKenguva, Gowtham1 aRout, Smruti, Rekha1 aKar, Ananya1 aGiri, Lopamudra1 aMahapatra, Sanat, Kumar1 aShaikh, Tabrez, R.1 aBaidya, Debjani1 aShelke, Nikita1 aDandela, Rambabu uhttps://library.ncl.res.in/content/synthesis-characterization-and-theoretical-investigations-newly-developed-molecular-salts