01626nas a2200289 4500008004100000022001400041245010400055210006900159260000900228300001400237520066700251653001000918653002200928653002600950653001700976653001600993653002001009100002501029700002101054700002401075700002501099700002101124700002701145700001801172700002101190856012501211 2019 eng d a1434-193X00aNeural anti-inflammatory natural product periconianone A: total synthesis and biological evaluation0 aNeural antiinflammatory natural product periconianone A total sy cAPR  a2376-23813 a

Total synthesis of periconianone A, an eremophilane-type sesquiterpenoid with impressive neural anti-inflammatory potential, has been accomplished. Diels-Alder/aldol strategy to construct tetrahydro-naphthalene-2,6-dione scaffold, allylic oxidation of dienone using DBU/O-2 and postulated biomimetic aldol reaction to construct 6/6/6 tricyclic system are the highlights of the present synthesis. Furthermore, the synthesized (+/-)-periconianone A and two close analogs were tested for their neural anti-inflammatory activity using various assays. In the course of our study we found a structurally simplified analog is superior to (+/-)-periconianone A.

10aAldol10aAllylic oxidation10aBiological evaluation10aCytotoxicity10aDiels-Alder10aPericonianone A1 aKalmode, Hanuman, P.1 aPatil, Suhag, S.1 aHandore, Kishor, L.1 aAthawale, Paresh, R.1 aDandela, Rambabu1 aVerma, Abhishek, Kumar1 aBasu, Anirban1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/neural-anti-inflammatory-natural-product-periconianone-total-synthesis-and-biological02374nas 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-permeation02013nas a2200229 4500008004100000245011400041210006900155260000800224300001400232490000700246520121200253100002301465700002401488700002101512700001901533700001701552700001901569700002101588700002401609700002401633856012601657 2022 eng d00aNovel crystal forms of Entresto: a supramolecular complex of trisodium sacubitril/valsartan hemi-pentahydrate0 aNovel crystal forms of Entresto a supramolecular complex of tris cOCT a7387-73930 v243 a

Entresto is a salt-cocrystal supramolecular complex with the chemical name trisodium sacubitril/valsartan hemi-pentahydrate for treating chronic heart failure and was approved by the US FDA in 2015. This multidrug complex was synthesized in our laboratory to investigate its polymorphic behavior. Different crystallization conditions, including various solvent systems, yielded different novel solid forms of Entresto (Form-I to Form-VI), including the reported form. All the novel solids are solvent-dependent and were reproducibly crystallized on a 10 g scale quantity. The 1H NMR spectra confirmed the 1 : 1 stoichiometry of the two drugs, namely, sacubitril and valsartan, in all the solid forms of the crystalline products. Powder X-ray diffraction and DSC analysis of the crystalline solids established that they are distinct crystalline forms. Stability studies under ambient conditions carried out over a one-year period showed higher stability for Form-I and Form-III compared to the other forms, including the innovator crystal form (labelled as Form-II). The novel crystal forms (notably Form-I and Form-III) exhibit higher stability and less hygroscopicity than the reported Form-II.

1 aShaikh, Tabrez, R.1 aGeorge, Christy, P.1 aBhukya, Priyanka1 aShelke, Nikita1 aPawar, Komal1 aGarai, Abhijit1 aDandela, Rambabu1 aGonnade, Rajesh, G.1 aNangia, Ashwini, K. uhttps://library.ncl.res.in/content/novel-crystal-forms-entresto-supramolecular-complex-trisodium-sacubitrilvalsartan-hemi02444nas 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-analysis02754nas a2200229 4500008004100000245008700041210006900128260000900197300001200206490000700218520202400225653001702249653001202266653001502278653000902293653001902302100002502321700002002346700002602366700002102392856011102413 2024 eng d00aNovel molecular adducts of an anti-cancer drug vandetanib with enhanced solubility0 aNovel molecular adducts of an anticancer drug vandetanib with en cJAN  a248-2600 v263 a

The solubility, permeability, and dissolution rate of an active pharmaceutical ingredient (API) are critical factors in determining its pharmacokinetic performance in oral dosage forms. Modifying these properties can potentially enhance the drug's pharmacokinetics. Vandetanib (VDTB), classified as a class II anti-cancer drug in the biopharmaceutical classification system (BCS), suffers from low solubility (0.008 mg mL-1) and an extended pharmacokinetic half-life (19 days), necessitating the administration of high doses, which leads to undesirable side effects. To address this issue, we have employed a crystal engineering approach to enhance the solubility of VDTB. We employed the liquid-assisted grinding (LAG) method followed by the slow evaporation technique to prepare novel solid forms of VDTB by incorporating various aliphatic dicarboxylic acids, including succinic acid (SUA), adipic acid (ADA), pimelic acid (PIA), azelaic acid (AZA), and sebacic acid (SBA). These newly obtained solid forms were characterized by SC-XRD, PXRD, TGA, and DSC experiments. The crystal structure analyses revealed a proton transfer between the carboxylic acid group of aliphatic acids and the N-methyl piperidine moiety of VDTB, confirming salt/adduct formation. Additionally, all of the molecular salts were stabilized by charge-assisted N+-HMIDLINE HORIZONTAL ELLIPSISO- hydrogen bonds, while the parent VDTB crystal structure is stabilised by N-HMIDLINE HORIZONTAL ELLIPSISN interactions. Moreover, the solubility and dissolution rate of these new solid forms were assessed in a pH 7.4 phosphate buffer medium, with the results indicating that all of the solid forms, except for VDTB:SBA, exhibited higher solubility compared to pure VDTB. These findings offer promising prospects for the development of an improved VDTB formulation with enhanced pharmacokinetic properties. Successful attempt to improve the solubility and dissolution rate of Vandetanib - an anti-cancer drug, by crystal engineering approach.

10aAmorfization10ahydrate10aParameters10aSalt10aThyroid-Cancer1 aBandaru, Ravi, Kumar1 aGiri, Lopamudra1 aKrishna, Gamidi, Rama1 aDandela, Rambabu uhttps://library.ncl.res.in/content/novel-molecular-adducts-anti-cancer-drug-vandetanib-enhanced-solubility