@article {46372, title = {Supramolecular synthon hierarchy in bumetanide cocrystals}, journal = {Acta Crystallographica A-Foundation and Advances}, volume = {70}, year = {2014}, month = {FEB}, pages = {C721}, type = {Meeting Abstract}, keywords = {Novel cocrystals of sulfonamide drug Bumetanide with carboxamides are developed based on supramolecular synthons approach}, issn = {2053-2733}, author = {Allu, Suryanarayana and Bolla, Geetha and Tothadi, Srinu and Nangia, Ashwini} } @article { ISI:000378715600002, title = {Pharmaceutical cocrystals: walking the talk}, journal = {Chemical Communications}, volume = {52}, number = {54}, year = {2016}, month = {MAY}, pages = {8342-8360}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

Pharmaceutical cocrystals belong to a sub-class of cocrystals wherein one of the components is a drug molecule (or an active pharmaceutical ingredient, API) and the second is a benign food or drug grade additive (generally regarded as safe, GRAS). The two components are hydrogen-bonded in a fixed stoichiometric ratio in the crystal lattice. In the past decade, pharmaceutical cocrystals have demonstrated significant promise in their ability to modify the physicochemical and pharmacokinetic properties of drug substances, such as the solubility and dissolution rate, bioavailability, particle morphology and size, tableting and compaction, melting point, physical form, biochemical and hydration stability, and permeability. In this feature review, we highlight some prominent examples of drug cocrystals which exhibit variable hardness/softness and elasticity/plasticity depending on coformer selection, improvement of solubility and permeability in the same cocrystal, increase of the melting point for solid formulation, enhanced color performance, photostability and hydration stability, and a longer half-life. Cocrystals of flavanoids and polyphenols can make improved pharmaceuticals and also extend to the larger class of nutraceuticals. The application of crystal engineering to assemble ternary cocrystals expands this field to drug-drug cocrystals which may be useful in multi-drug resistance, mitigating side effects of drugs, or attenuating/enhancing drug action synergistically by rational selection. The advent of new techniques for structural characterization beyond the standard X-ray diffraction will provide a better understanding of drug phases which are at the borderline of crystalline-amorphous nature and even newer opportunities in the future.

}, issn = {1359-7345}, doi = {10.1039/c6cc02943d}, author = {Bolla, Geetha and Nangia, Ashwini} } @article {43716, title = { Acemetacin cocrystal structures by powder X-ray diffraction}, journal = {Iucrj}, volume = {4}, year = {2017}, month = {MAY}, pages = {206-214}, type = {Article}, abstract = {Cocrystals of acemetacin drug (ACM) with nicotinamide (NAM), p-aminobenzoic acid (PABA), valerolactam (VLM) and 2-pyridone (2HP) were prepared by melt crystallization and their X-ray crystal structures determined by high-resolution powder X-ray diffraction. The powerful technique of structure determination from powder data (SDPD) provided details of molecular packing and hydrogen bonding in pharmaceutical cocrystals of acemetacin. ACM-NAM occurs in anhydrate and hydrate forms, whereas the other structures crystallized in a single crystalline form. The carboxylic acid group of ACM forms theacid-amide dimer three-point synthon R-3(2)(9) R-2(2)(8) R-3(2)(9) with three different syn amides (VLM, 2HP and caprolactam). The conformations of the ACM molecule observed in the crystal structures differ mainly in the mutual orientation of chlorobenzene fragment and the neighboring methyl group, being anti (type I) or syn (type II). ACM hydrate, ACM-NAM, ACM-NAM-hydrate and the piperazine salt of ACM exhibit the type I conformation, whereas ACM polymorphs and other cocrystals adopt the ACM type II conformation. Hydrogen-bond interactions in all the crystal structures were quantified by calculating their molecular electrostatic potential (MEP) surfaces. Hirshfeld surface analysis of the cocrystal surfaces shows that about 50\% of the contribution is due to a combination of strong and weak O center dot center dot center dot H, N center dot center dot center dot H, Cl center dot center dot center dot H and C center dot center dot center dot H interactions. The physicochemical properties of these cocrystals are under study.}, doi = {10.1107/S2052252517002305}, author = {Bolla, Geetha and Chernyshev, Vladimir and Nangia, Ashwini} } @article {43818, title = {Supramolecular synthons in bumetanide cocrystals and ternary products}, journal = {Crystal Growth \& Design}, volume = {17}, year = {2017}, month = {AUG}, pages = {4225-4236}, type = {Article}, abstract = {A novel design strategy for cocrystals of the diuretic sulfonamide drug bumetanide (BUM) with carboxamides is reported based on reliable supramolecular synthons. Binary cocrystals of BUM with pyridine carboxamides, pyridones, and cytosine were obtained by solvent assisted grinding followed by solution crystallization. All cocrystal structures exhibit hydrogen bonding of the coformer with the carboxylic acid group of BUM via heterosynthons which replace the acid homodimer in the drug crystal structure. Pyridones are inserted as N-H center dot center dot center dot O dimers which are in turn bonded to the acid group of BUM, while the pyridine amide coformers interact via the acid amide heterosynthon. Cocrystal polymorphs were obtained for bumetanide isonicotinamide cocrystal structure with the sulfonamide pyridine and sulfonamide acid synthons. Careful crystal packing analysis of BUM structure and nine new binary adducts gave an idea for the design ternary cocrystals, and subsequently four new ternary crystalline products were crystallized. Whereas the binary cocrystal structures were confirmed by single crystal diffraction, the ternary combinations were chatacterized by their unique powder X-ray diffraction patterns as well as by thermal and spectroscopic techniques.}, doi = {10.1021/acs.cgd.7b00531}, author = {Allu, Suryanarayana and Bolla, Geetha and Tothadi, Srinu and Nangia, Ashwini} } @article {45365, title = { Novel pharmaceutical salts of albendazole}, journal = {Crystengcomm}, volume = {20}, year = {2018}, month = {NOV}, pages = { 6394-6405}, type = {Article}, abstract = {Albendazole (ABZ) is a class II safe and effective antihelmintic drug in the benzimidazole group according to the BCS (Biopharmaceutics Classification System) with low solubility (9 mg L-1) and high permeability (log P 2.54). Novel salts and salt hydrates of ABZ are reported with benzene and p-toluene sulfonic acid (BSA, PTSA), as well as carboxylic acids such as oxalic acid (OA), maleic acid (MLE), L-tartaric acid (LTA), 2,6-dihydroxybenzoic acid (2,6-DHBA), and 2,4,6-trihydroxybenzoic acid (2,4,6-THBA). The products ABZ-BSA, ABZ-BSA-H, ABZ-PTSA, ABZ-PTSA-H, ABZ-OA-H and ABZ-2,6-DHBA were confirmed by single crystal X-ray diffraction. In the hydrate structures (designated as -H), the water molecule acts as a bridge in the hydrogen bonding network. The salt formation of ABZ-MLE, ABZ-LTA, and ABZ-2,4,6-THBA was confirmed by N-15 ss-NMR based on the chemical shift change of ca. 50 ppm. The sulfonate salt hydrates exhibit 2D isostructurality, and position disorder in the thiopropyl group in the drug crystal structure was not observed in the salts. Crystal lattice energies were calculated for the MLE, LTA, and 2,4,6-THBA complexes of ABZ to confirm the molecular salt formation. The cocrystals of ABZ with the hydroxybenzene carboxylic acids are novel salts in the benzimidazole drugs class.}, author = {Bolla, Geetha and Nangia, Ashwini} } @article {46141, title = {Role of hydrogen bonding in cocrystals and coamorphous solids: indapamide as a case study}, journal = {Crystengcomm}, volume = {21}, year = {2019}, month = {APR }, pages = {2043-2048}, type = {Article}, abstract = {

The stronger sulfonamide-pyridine (SO2NH2 center dot center dot center dot N-Py) and sulfonamide-carboxamide (SO2NH2 center dot center dot center dot O = C-NH) hydrogen bonds direct the formation of cocrystals, while the weaker sulfonamide-amine (SO2NH2 center dot center dot center dot N-H) hydrogen bond results in coamorphous products. IDP-PIP and IDP-ARG coamorphous solids exhibit remarkable stability under accelerated conditions.

}, issn = {1466-8033}, doi = {10.1039/c8ce01075g}, author = {Allu, Suryanarayana and Suresh, Kuthuru and Bolla, Geetha and Mannava, M. K. Chaitanya and Nangia, Ashwini} } @article {46069, title = {Supramolecular synthon hierarchy in sulfonamide cocrystals with syn-amides and N-oxides}, journal = {IUCRJ}, volume = {6}, year = {2019}, month = {JUL}, pages = {751-760}, type = {Article}, abstract = {

Sulfonamide drugs are well known antibacterial and antimicrobial molecules for pharmaceutical development. Building a library of suitable supramolecular synthons for the sulfonamide functional group and understanding their crystal structures with partner coformer molecules continues to be a challenge in crystal engineering. Although a few sulfonamide cocrystals with amides and N-oxides have been reported, the body of work on sulfonamide synthons is limited compared with those that have carboxylic acids and carboxamides. To address this structural gap, the present work is primarily focused on sulfonamide-lactam and sulfonamide-syn-amide synthons with drugs such as celecoxib, hydrochlorothiazide and furosemide. Furthermore, the electrostatic potential of previously reported cocrystals has been recalculated to show that the negative electrostatic potential on the lactam and syn-amide O atom is higher compared with the charge on carboxamide and pyridine N-oxide O atoms. The potential of sulfonamide molecules to form cocrystals with syn-amides and lactams are evaluated in terms of the electrostatic potential energy for the designed supramolecular synthons.

}, keywords = {cocrystals, crystal engineering, sulfonamides, supramolecular synthons, syn-amides}, issn = {2052-2525}, doi = {10.1107/S2052252519005037}, author = {Bolla, Geetha and Nangia, Ashwini} } @article {46974, title = {Novel pharmaceutical cocrystals and salts of bumetanide}, journal = {Crystal Growth \& Design}, volume = {20}, year = {2020}, month = {FEB}, pages = {793-803}, type = {Article}, abstract = {

New crystalline forms of bumetanide, namely, four cocrystals, two salts, and one salt-cocrystal were crystallized. Urea and lactams such as valerolactam, caprolactam, and N-methyl caprolactam formed cocrystals with bumetanide, whereas 4-aminopyridine gave a salt. Piperazine afforded a salt hydrate, and 5-fluorocytosine gave a salt-cocrystal. The supramolecular synthons in bumetanide-lactam cocrystals are an amide dimer between drug and coformer, and acid homo dimer between bumetanide molecules. In bumetanide salts, the acid proton is transferred from bumetanide to coformer amine, whereas in bumetanide salt-cocrystal proton transfer and free acid were observed in the crystal structure. Similarly, the cytosine salt-cocrystal of bumetanide and fluorocytosine also gave a salt-cocrystal adduct. The acid proton of bumetanide is transferred to the 2-amino pyridine base of cytosine as a salt, and on the other side of the drug molecule the sulfonamide interacts with the syn amide part of cytosine. Furthermore, solubility, dissolution, and diffusion membrane permeability experiments were performed on all new solid forms. The piperazine salt shows high dissolution and permeability crossover when compared to other binary forms of bumetanide.

}, issn = {1528-7483}, doi = {10.1021/acs.cgd.9b01195}, author = {Allu, Suryanarayana and Bolla, Geetha and Tothadi, Srinu and Nangia, Ashwini K.} }