Geetha Bolla

Celecoxib cocrystal polymorphs with cyclic amides: synthons of a sulfonamide drug with carboxamide coformers

The trimorphic cocrystals of celecoxib with δ-valerolactam contain sulfonamide dimers and catemers together with carboxamide dimers, whereas the caprolactam cocrystal is sustained by a SO2N–H⋯H–NOC heterosynthon. The alternation of synthons with even–odd ring coformers offers a crystal engineering approach to sulfonamide–carboxamide cocrystals.

Acemetacin polymorphs: a rare case of carboxylic acid catemer and dimer synthons

Acemetacin is the first example of an API polymorph with a carboxylic acid catemer and dimer O–H⋯O synthons. The auxiliary stabilization to the catemer motif from stronger C–H⋯O and C–Cl⋯O interactions compared to those in the dimer structure is discussed for a polymorph pair. The crystal structure of the stable dimer polymorph was solved by structure determination from powder X-ray diffraction data (SDPD).

Acemetacin cocrystals and salts: structure solution from powder X-ray data and form selection of the piperazine salt

Multi-component crystals of the anti-inflammatory drug acemetacin were prepared by melt crystallization and their X-ray crystal structures solved using single-crystal and high-resolution powder X-ray diffraction (PXRD) data. The acemetacin–para-aminobenzoic acid adduct and the acemetacin piperazine salt are stable to hydration in the aqueous medium (up to 24 h).

Binary and ternary cocrystals of sulfa drug acetazolamide with pyridine carboxamides and cyclic amides

The first report of a ternary cocrystal acetazolamide–nicotinamide–pyridone (1:1:1) for a sulfonamide drug with amide coformers.

Modularity and three-dimensional isostructurality of novel synthons in sulfonamide–lactam cocrystals

Novel supramolecular synthons for primary sulfonamides with cyclic amides (GRAS coformers) are introduced for the crystal engineering of pharmaceutical cocrystals of sulfa drugs. The cocrystals of this model study exhibit isostructurality and isosynthons mediated by SO2NH2⋯CONH hydrogen bonding.

Can we exchange water in a hydrate structure: a case study of etoricoxib

Novel crystalline forms of etoricoxib (ETR) with pharmaceutically acceptable coformers (generally regarded as safe, GRAS), such as glutaric acid (1:1), adipic acid (2:1), suberic acid (1:1), and caprolactam, were co-crystallized. The solid forms were prepared from ETR hemihydrate form I and characterized by powder XRD, DSC, and IR, and finally confirmed by single crystal X-ray diffraction. The exchange of water with an organic acid coformer in the crystal structure is explained by lattice energy calculations.

Acemetacin cocrystal structures by powder X-ray diffraction

Acemetacin cocrystals were prepared by melt crystallization and their crystal structures determined by high-resolution powder X-ray diffraction. The difficult to obtain single crystals for the acemetacin family is overcome by structure determination from powder data.

Role of hydrogen bonding in cocrystals and coamorphous solids: indapamide as a case study

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

Novel pharmaceutical salts of Albendazole

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 15N 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.

Supramolecular synthon hierarchy in bumetanide co-crystals

Active pharmaceutical ingredients (API) cocrystals are much important in pharmaceutical industry to fine tune the physicochemical properties such as solubility, dissolution, bioavailability and stability. to design of new cocrystals, basic understanding of the functional groups attached to the given molecules, complementary hydrogen bonds and molecular crystal packing of the API and coformer is essential. recently; we synthesized sulfonamide cocrystals with lactams, syn−amides and pyridine carboxamides from binary to ternary cocrystals. The new supramolecular synthon strategy was successfully developed for sulfonamide functional group and applied on acetazolamide drug. in continuation of our previous work to explore more about new supramolecular synthons, our focus moved towards diuretic sulfonamide drug ‘Bumetanide (BUM)’ with carboxamides are developed based on supramolecular synthons approach. Binary cocrystals of BUM with pyridine carboxamides, pyridones, and cytosine were obtained by solvent assist grinding followed by solution crystallization. All cocrystals are formed by proper insertion of coformers in the acid-acid homo dimer of BUM to achieve new supramolecular synthons. Pyridones are inserted acid-acid homo dimer of BUM as pyridone dimers. Pyridine amide coformers are always interacted with acid of BUM to form acid−amide dimer. Cocrystal polymorphs are obtained with Bumetanide–Isonicotinamide combination and show rare sulfonamide−pyridine, sulfonamide−acid synthon. By careful crystal packing analysis of single component BUM and nine new binary adducts gave an idea to design ternary cocrystals and finally four new ternary crystalline materials were synthesized. Single component crystals of BUM, all binary cocrystals were characterized PXRD, IR, DSC and finally all the binary adducts (except nicotinamide) confirmed by single crystal analysis.