Structure and Solid‐State Chemistry of Anhydrous and Hydrated Crystal forms of the Trimethoprim‐Sulfamethoxypyridazine 1:1 Molecular Complex

Bettinetti, Giampiero; Caira, Mino R.; Callegari, A.; Merli, Marcello; Sorrenti, Milena; Tadini, C.

doi:10.1002/(sici)1520-6017(200004)89:4<478::aid-jps5>3.0.co;2-5

Cited by 57 publications

(35 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the crystalline state, hydrogen bonds are accountable for the creation of families of molecular networks with the same molecular components or with different molecular components (multiple component crystals or cocrystals). [5][6][7][8][9][10][11][12][13][14][15] The cocrystals are stabilized through a variety of different intermolecular interactions including hydrogen bonds, aromatic p-stacking, and van der Waals forces, and unlike salt formation, no proton transfer occurs between the API and the guest molecule. 16 Slow evaporation and grinding are the most commonly used techniques for producing cocrystals.…”

Section: 4mentioning

confidence: 99%

Identification of a new cocrystal of citric acid and paracetamol of pharmaceutical relevance

et al. 2011

View full text Add to dashboard Cite

Cocrystals have been increasingly recognized as an attractive alternative delivery form for solid drug products. In this work, Raman spectroscopy, X-ray powder diffraction/X-ray crystallography, and differential scanning calorimetry have been used to study the phenomenon of cocrystal formation in stoichiometric mixtures of citric acid with paracetamol. Raman spectroscopy was particularly useful for the characterization of the products and was used to determine the nature of the interactions in the cocrystals. It was observed that little change in the vibrational modes associated with the phenyl groups of the respective reactants took place upon cocrystal formation but changes in intensities of the vibrational modes associated with the amide and the carboxylic acid groups were observed upon cocrystal formation. Several new vibrational bands were identified in the cocrystal which were not manifest in the raw material and could be used as diagnostic features of cocrystal formation. An understanding of the effects of cocrystal formation on the vibrational modes was obtained by the complete assignment of the spectra of the starting materials and of the cocrystal component. The results show that the cocrystals was obtained in a 2 : 1 molar ratio of paracetamol to citric acid. The asymmetric unit of the crystal contains two paracetamol molecules hydrogen-bonded to the citric acid; one of these acts as a phenolic-OH hydrogen bond donor to the carbonyl of a carboxylic acid arm of citric acid. In contrast, the other phenolic-OH acts as a hydrogen bond acceptor from the quaternary C-OH of citric acid.

show abstract

Section: 4mentioning

confidence: 99%

Identification of a new cocrystal of citric acid and paracetamol of pharmaceutical relevance

et al. 2011

View full text Add to dashboard Cite

show abstract

“…It is important to note that cocrystals are a homogeneous phase of stoichiometric composition and not a mixture of pure component crystalline phases. Key questions in the discovery of families of cocrystals are: (1) do cocrystals offer any advantages over other solid-state forms, (2) what are the criteria for cocrystal former selection, (3) can cocrystal screening and cocrystallization methods be theoretically based, and (4) can cocrystals form as a result of stresses encountered during pharmaceutical processes and storage? The research presented in this manuscript will address the last question.…”

Section: Introductionmentioning

confidence: 99%

Cocrystal Formation during Cogrinding and Storage is Mediated by Amorphous Phase

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Several structures of solvates are also present, along with chlorohydrate/bromohydrate structures. Pharmaceutical cocrystal structures of neutral trimethoprim with 3,3-tetramethyleneglutarimide (Ton, 2014), glutarimide and 3,3-dimethylglutarimide (Ton & Egert, 2015), sulfadimidine , saccharine , barbital (Brogden et al, 1982), barbituric acid (Muthiah et al, 2007), 2aminoterephtalic acid (Delori & Jones, 2011) and sulfamethoxazole (Giuseppetti & Tadini, 1980) are reported as well as pharmaceutical salts of charged trimethoprim with sulfonamide derivatives sulfametrole (Giuseppetti et al, 1994), sulfamethoxazole (Nakai et al, 1984) and sulfamethoxypyridazine (Bettinetti et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Structural and energy insights on solid-state complexes with trimethoprim: a combined theoretical and experimental investigation

Tilborg

Carletta

2015

Acta Crystallogr Sect B

View full text Add to dashboard Cite

We present here a new structure of a 1:1 salt of trimethoprim with hemifumarate, highlighted by single-crystal X-ray diffraction and computational conformational studies. This salt was formed during cocrystallization assays conducted to combine trimethoprim and other APIs whose combination exhibits interesting properties. Theoretical in vacuo investigations have been performed on the organic salt through a DFT two-dimensional conformational scan of torsion angles between the two aromatic moieties of trimethoprim. The evaluation of relative energies for hydrogen-bond interactions in the structure has also been performed. Comparison with conformational data from structures implying trimethoprim retrieved from the Cambridge Structural Database (CSD) shows good agreement with theoretical results, proving the validity of vacuum ab initio calculations in describing the energetic landscape of the molecule and thereby gain initial insight into the prediction process for possible new conformations and therefore potential new polymorphs.

show abstract

Structure and Solid‐State Chemistry of Anhydrous and Hydrated Crystal forms of the Trimethoprim‐Sulfamethoxypyridazine 1:1 Molecular Complex

Cited by 57 publications

References 24 publications

Identification of a new cocrystal of citric acid and paracetamol of pharmaceutical relevance

Identification of a new cocrystal of citric acid and paracetamol of pharmaceutical relevance

Cocrystal Formation during Cogrinding and Storage is Mediated by Amorphous Phase

Structural and energy insights on solid-state complexes with trimethoprim: a combined theoretical and experimental investigation

Contact Info

Product

Resources

About