@article {47312, title = {Synthesis, crystal structure and Hirshfeld surface analysis of the hydrated form of N{\textquoteright}, N-(1,4-phenylenebis(methanylylidene) di(iso-nicotinic hydrazide)}, journal = {Chemical Data Collections}, volume = {28}, year = {2020}, month = {AUG}, type = {Article}, abstract = {

The title compound, C20H16N6O2\ was synthesized by reflux with isonicotinic hydrazide and terephthaldehyde in ethanol solvent with the acidic condition. The single-crystal X-ray structure determination of the title compound,\ N, N-(1,4-phenylene bis (methanylylidene) di(iso-nicotinic hydrazide), reveals that the molecule crystallizes in center of symmetry with water molecules (Dihydrated form, C20H16N6O2.2H2O) through N-H...O and C-H...O hydrogen bondings. Further, the crystal structure is stabilized by O-H...O and weak C-H...N hydrogen bondings with the formation of infinite chain and dimer. Further, surface analysis and fingerprint plot reveal that the significant hydrogen bonding such as H{\textbullet}{\textbullet}{\textbullet}O (15.9\%) and N{\textbullet}{\textbullet}{\textbullet}H (11.4\%) interactions play the most crucial role for its molecular packing.

}, doi = {10.1016/j.cdc.2020.100401}, author = {Ingle, Kapil S. and Mohurle, Smital A. and Bairagi, Keshab M. and Shaikh, Tabrez R. and Venugopala, Katharigatta N. and Chandrashekharappa, Sandeep and Gonnade, Rajesh G. and Nayak, Susanta K.} } @article {48175, title = {Novel crystal forms of Entresto: a supramolecular complex of trisodium sacubitril/valsartan hemi-pentahydrate}, journal = {Crystengcomm}, volume = {24}, year = {2022}, month = {OCT}, pages = {7387-7393}, type = {Article}, abstract = {

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.

}, doi = {10.1039/d2ce01009g}, author = {Shaikh, Tabrez R. and George, Christy P. and Bhukya, Priyanka and Shelke, Nikita and Pawar, Komal and Garai, Abhijit and Dandela, Rambabu and Gonnade, Rajesh G. and Nangia, Ashwini K.} } @article {49376, title = {Exploring novel cocrystals of milrinone: a cardioprotective drug combined with nutraceuticals and an NSAID}, journal = {CrystEngComm}, volume = {27}, year = {2024}, month = {DEC}, pages = {138-145}, type = {Article}, abstract = {

Milrinone is a bipyridine phosphodiesterase (PDE) inhibitor of the second generation. It{\textquoteright}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{\textquoteright}s solubility, which may have a positive impact on its synergistic cardioprotective effects.

}, doi = {10.1039/d4ce00990h}, author = {Kenguva, Gowtham and Rekha Rout, Smruti and Shaikh, Tabrez R. and Baidya, Debjani and Shelke, Nikita and Sanphui, Palash and Dandela, Rambabu} } @article {49383, title = {New binary adducts of panobinostat with different carboxylic acid based NSAIDs: structural analysis and physicochemical properties investigation}, journal = {ChemistrySelect}, volume = {9}, year = {2024}, month = {NOV}, pages = {e202403539}, type = {Article}, abstract = {

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.

}, keywords = {Drug-drug salts, Heteromeric interactions, Hydrogen bond, Non-steroidal anti-inflammatory drugs, Panobinostat}, issn = {2365-6549}, doi = {10.1002/slct.202403539}, author = {Kenguva, Gowtham and Rout, Smruti Rekha and Kar, Ananya and Giri, Lopamudra and Shaikh, Tabrez R. and Jadab, Madhusmita and Pal, Satyanarayan and Dandela, Rambabu} } @article {49284, title = {Structural insights into ketanserin salts with aliphatic acids and their physiochemical properties}, journal = {CRYSTENGCOMM}, volume = {26}, year = {2024}, month = {NOV }, pages = {6260-6268}, type = {Journal Article}, keywords = {PHARMACEUTICAL COCRYSTAL, SEROTONIN, SHYDROCHLOROTHIAZIDE, solubility}, doi = {10.1039/d4ce00738g}, author = {Kenguva, Gowtham and Rout, Smruti Rekha and Shaikh, Tabrez R. and Baidya, Debjani and Shelke, Nikita and Sanphui, Palash and Dandela, Rambabu} } @article {49692, title = {Cocrystals of the highly potent sickle cell anemia drug voxelotor with trimesic acid: a substantial enhancement in in vitro dissolution performance at physiological pH}, journal = {Crystal Growth \& Design}, volume = {25}, year = {2025}, month = {MAY}, pages = {4405-4425}, type = {Article}, abstract = {

Global Blood Therapeutic{\textquoteright}s (GBT{\textquoteright}s) Voxelotor is an investigational oral therapy for treating sickle cell anemia. It functions by increasing the affinity between hemoglobin and oxygen, thereby preventing the sickling of red blood cells and altering the disease{\textquoteright}s pathology. The US FDA has approved Voxelotor for the treatment of sickle cell anemia and granted it an orphan drug status. However, Voxelotor is classified as a BCS class II, indicating poor water solubility. The current study explores the enhancement of Voxelotor{\textquoteright}s water solubility by forming cocrystals with trimesic acid (TMA). Novel cocrystals, cocrystal solvates, and hydrates of Voxelotor (Vox) with trimesic acid (TMA) have been developed to improve their solubility. The new solids were characterized using PXRD, DSC, TGA, XPS, HSM, and single-crystal X-ray diffraction studies, and the intermolecular interactions were quantified using Hirshfeld surface analysis. Detailed crystallographic analysis revealed strong O-H center dot center dot center dot N hydrogen bonding interactions between Vox and TMA, primarily involving the COOH functional group of TMA and the pyridine or pyrazole groups of Vox. Additionally, TMA molecules participate in further hydrogen bonding-either with themselves or with solvates, including hydrates, through mono- or dimeric O-H center dot center dot center dot O H-bonding synthons. In vitro solubility studies demonstrated a significant increase in the solubility of Voxelotor in the Vox-TMA cocrystals compared to the pristine drug at physicochemical pH 4.5 and 6.8. Stability studies confirmed that the nonsolvated multicomponent crystal retains their structural integrity under nonambient conditions without undergoing polymorphic phase transitions. In contrast, the solvated crystals, including hydrates, undergo phase transitions within the temperature range of 100-130 degrees C, losing solvents and converting into one of the nonsolvated cocrystal forms. These findings suggest that the novel Vox-TMA cocrystals have the potential to enhance the therapeutic performance and clinical utility of Voxelotor.

}, issn = {1528-7483}, doi = {10.1021/acs.cgd.5c00300}, author = {Khan, Akram A. and Shaikh, Tabrez R. and George, Christy P. and Gonnade, Rajesh G.} } @article {49501, title = {Confined impinging jet reactor for high-throughput continuous flow mononitration of salicylic acid}, journal = {Organic Process Research \& Development}, volume = {29}, year = {2025}, month = {JAN}, pages = {479-489}, type = {Article}, abstract = {

Novel approach is reported for highly efficient continuous mononitration of salicylic acid using confined impinging jet reactor (CIJR) with a vent. Initially, controlled semibatch reactions are optimized to achieve complete conversion and formation of mononitro products with very high selectivity for 5-nitrosalicylic acid (5-NSA). Further, the combination of computational fluid dynamics simulations and experiments is employed to optimize CIJR design and operating flow conditions, suitable to yield only mononitro products with excellent control over mixing, heat transfer, and liberation of fumes during continuous flow reaction. Detailed analysis of internal flow patterns, rate of heat generation, and concentration distribution inside the CIJR facilitated the optimization of present exothermic reaction in a safe manner. In less than a minute, complete salicylic acid (SA) conversion with good yield and better selectivity for 5-NSA is achieved using the CIJR. Safety and clogging issues are addressed effectively, even at a relatively lower mole ratio (1:5) of SA:acetic acid (AcOH). The present approach is quite scalable using the numbering-up strategy, with advantages viz. nonfouling, high throughput, and the small footprint of CIJR.

}, keywords = {computational fluid dynamics, confined impinging jet reactor, high-throughput synthesis, salicylic acid nitration}, issn = {1083-6160}, doi = {10.1021/acs.oprd.4c00467}, author = {Khan, Muzammilanwar S. and Shaikh, Tabrez R. and Kulkarni, Sphurti P. and Patil, Abhishek A. and Kulkarni, Amol A.} } @article {49517, title = {Synthesis, characterization and theoretical investigations of the newly developed molecular salts of an anti-psychotic drug (Penfluridol)}, journal = {Journal of Molecular Structure}, volume = {1328}, year = {2025}, month = {APR}, pages = {141392}, type = {Article}, abstract = {

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{\textquoteright} 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.

}, keywords = {Anti-psychotic drug, Hydrogen bond, Liquid-assisted grinding (LAG), solubility}, issn = {0022-2860}, doi = {10.1016/j.molstruc.2025.141392}, author = {Kenguva, Gowtham and Rout, Smruti Rekha and Kar, Ananya and Giri, Lopamudra and Mahapatra, Sanat Kumar and Shaikh, Tabrez R. and Baidya, Debjani and Shelke, Nikita and Dandela, Rambabu} }