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Application of vibrational spectroscopy supported by theoretical calculations in identification of amorphous and crystalline forms of cefuroxime axetil.

Talaczyńska A, Lewandowska K, Jelińska A, Garbacki P, Podborska A, Zalewski P, Oszczapowicz I, Sikora A, Kozak M, Cielecka-Piontek J - ScientificWorldJournal (2015)

Bottom Line: FT-IR and Raman scattering spectra of cefuroxime axetil were proposed for identification studies of its crystalline and amorphous forms.An analysis of experimental spectra was supported by quantum-chemical calculations performed with the use of B3LYP functional and 6-31G(d,p) as a basis set.The geometric structure of a cefuroxime axetil molecule, HOMO and LUMO orbitals, and molecular electrostatic potential were also determined by using DFT (density functional theory).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.

ABSTRACT
FT-IR and Raman scattering spectra of cefuroxime axetil were proposed for identification studies of its crystalline and amorphous forms. An analysis of experimental spectra was supported by quantum-chemical calculations performed with the use of B3LYP functional and 6-31G(d,p) as a basis set. The geometric structure of a cefuroxime axetil molecule, HOMO and LUMO orbitals, and molecular electrostatic potential were also determined by using DFT (density functional theory). The benefits of applying FT-IR and Raman scattering spectroscopy for characterization of drug subjected to degradation were discussed.

No MeSH data available.


Chemical structure of cefuroxime axetil.
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Related In: Results  -  Collection


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fig1: Chemical structure of cefuroxime axetil.

Mentions: Cefuroxime axetil belongs to the second generation of cephalosporins characterized by a broad spectrum of antibacterial activity and is used as an oral prodrug [1]. Cefuroxime axetil contains various isomeric centers and occurs in crystalline and amorphous forms. The stereochemical properties of cefuroxime axetil are essential for its antibacterial activity and affinity to biological membranes. A syn-geometric isomer demonstrates considerable resistance to β-lactamases and is easily transported while an anti-isomer of cefuroxime axetil is deactivated by cephalosporinases [2, 3]. Due to the poor solubility of cefuroxime axetil content, studies of polymorphs in drug products are required. The abbreviated new drug application (ANDA) has approved cefuroxime axetil as an amorphous dispersion or an amorphous/crystalline mixture following the expiry of patent protection and the appearance of generic products. It is suggested that the crystalline content in the mixture of cefuroxime axetil may “seed” crystallization of the amorphous form and so increase the content of the crystalline form that is known to be less soluble and bioavailable [4]. The literature does not provide reports on analytical methods allowing precise and valid characterization of polymorphic forms of cefuroxime axetil. The methods that have been proposed, including those recommended by USP, employ polarizing microscopy [5]. They fail to supply the data necessary to study the polymorphism of cefuroxime axetil during the manufacture of batch-to-batch drug products as well as their control throughout drug product shelf-life. The development of an analytical method for examining cefuroxime axetil polymorphism needs to take into consideration the susceptibility of the drug to degradation [6, 7]. The stability of cefuroxime axetil has been studied, including evaluation of differences in kinetic degradation, adsorption, and photoisomerisation of diastereoisomers [8–10]. It is possible to suggest that interring stresses are one of the reasons of instability of β-lactam analogs (Figure 1).


Application of vibrational spectroscopy supported by theoretical calculations in identification of amorphous and crystalline forms of cefuroxime axetil.

Talaczyńska A, Lewandowska K, Jelińska A, Garbacki P, Podborska A, Zalewski P, Oszczapowicz I, Sikora A, Kozak M, Cielecka-Piontek J - ScientificWorldJournal (2015)

Chemical structure of cefuroxime axetil.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4306215&req=5

fig1: Chemical structure of cefuroxime axetil.
Mentions: Cefuroxime axetil belongs to the second generation of cephalosporins characterized by a broad spectrum of antibacterial activity and is used as an oral prodrug [1]. Cefuroxime axetil contains various isomeric centers and occurs in crystalline and amorphous forms. The stereochemical properties of cefuroxime axetil are essential for its antibacterial activity and affinity to biological membranes. A syn-geometric isomer demonstrates considerable resistance to β-lactamases and is easily transported while an anti-isomer of cefuroxime axetil is deactivated by cephalosporinases [2, 3]. Due to the poor solubility of cefuroxime axetil content, studies of polymorphs in drug products are required. The abbreviated new drug application (ANDA) has approved cefuroxime axetil as an amorphous dispersion or an amorphous/crystalline mixture following the expiry of patent protection and the appearance of generic products. It is suggested that the crystalline content in the mixture of cefuroxime axetil may “seed” crystallization of the amorphous form and so increase the content of the crystalline form that is known to be less soluble and bioavailable [4]. The literature does not provide reports on analytical methods allowing precise and valid characterization of polymorphic forms of cefuroxime axetil. The methods that have been proposed, including those recommended by USP, employ polarizing microscopy [5]. They fail to supply the data necessary to study the polymorphism of cefuroxime axetil during the manufacture of batch-to-batch drug products as well as their control throughout drug product shelf-life. The development of an analytical method for examining cefuroxime axetil polymorphism needs to take into consideration the susceptibility of the drug to degradation [6, 7]. The stability of cefuroxime axetil has been studied, including evaluation of differences in kinetic degradation, adsorption, and photoisomerisation of diastereoisomers [8–10]. It is possible to suggest that interring stresses are one of the reasons of instability of β-lactam analogs (Figure 1).

Bottom Line: FT-IR and Raman scattering spectra of cefuroxime axetil were proposed for identification studies of its crystalline and amorphous forms.An analysis of experimental spectra was supported by quantum-chemical calculations performed with the use of B3LYP functional and 6-31G(d,p) as a basis set.The geometric structure of a cefuroxime axetil molecule, HOMO and LUMO orbitals, and molecular electrostatic potential were also determined by using DFT (density functional theory).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.

ABSTRACT
FT-IR and Raman scattering spectra of cefuroxime axetil were proposed for identification studies of its crystalline and amorphous forms. An analysis of experimental spectra was supported by quantum-chemical calculations performed with the use of B3LYP functional and 6-31G(d,p) as a basis set. The geometric structure of a cefuroxime axetil molecule, HOMO and LUMO orbitals, and molecular electrostatic potential were also determined by using DFT (density functional theory). The benefits of applying FT-IR and Raman scattering spectroscopy for characterization of drug subjected to degradation were discussed.

No MeSH data available.