The impact of the size of acetylated cyclodextrin on the stability of amorphous metronidazole

Minecka, Aldona; Tarnacka, Magdalena; Jurkiewicz, Karolina; Hachuła, Barbara; Wrzalik, R.; Bródka, A.; Kamiński, Kamil; Kamińska, Ewa

doi:10.1016/j.ijpharm.2022.122025

Cited by 4 publications

(5 citation statements)

References 32 publications

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“…As it is impossible to obtain amorphous MTZ using the standard vitrification method due to its rapid crystallization after melting, we collected the FTIR spectrum of the molten MTZ to detect spectral differences between the crystalline and liquid samples. The spectra of the crystalline and molten MTZ, as well as three PVP samples, together with the assignment of characteristic bands to the appropriate molecular vibrations [ 49 , 60 , 61 , 62 , 63 ], are given in the SMs (see Figure S7 ), whereas the spectra of MTZ- PVP BMs in the supercooled liquid/or glassy and crystalline states, recorded in the regions of 3800–2400 and 1800–400 cm −1 , are shown in Figures S8–S10 . It is worth mentioning that in the crystal, MTZ molecules are linked through O—H···N hydrogen bonds and stabilized by C—H···O weak interactions, forming chains propagating/extending along the c-axis direction [ 64 ].…”

Section: Resultsmentioning

confidence: 99%

“…Briefly, one can stress that the amorphization of this active substance is a difficult task. For example, it is not possible to obtain it in the glassy form using the standard vitrification method due to its immediate crystallization after melting [ 49 ]. So far, only one successful attempt to produce a stable amorphous MTZ in ASDs has been reported.…”

Section: Introductionmentioning

confidence: 99%

“…So far, only one successful attempt to produce a stable amorphous MTZ in ASDs has been reported. Minecka et al have demonstrated that acetylated cyclodextrins (especially the β form) can effectively inhibit the recrystallization of MTZ from the glassy state [ 49 ]. Therefore, further exploration of novel EXCs (both low- and high-molecular-weight) effectively stabilizing amorphous MTZ appears fully justified.…”

Section: Introductionmentioning

confidence: 99%

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The Impact of Various Poly(vinylpyrrolidone) Polymers on the Crystallization Process of Metronidazole

Orszulak,

Lamrani,

Tarnacka

et al. 2024

Pharmaceutics

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In this paper, we propose one-step synthetic strategies for obtaining well-defined linear and star-shaped polyvinylpyrrolidone (linPVP and starPVP). The produced macromolecules and a commercial PVP K30 with linear topology were investigated as potential matrices for suppressing metronidazole (MTZ) crystallization. Interestingly, during the formation of binary mixtures (BMs) containing different polymers and MTZ, we found that linear PVPs exhibit maximum miscibility with the drug at a 50:50 weight ratio (w/w), while the star-shaped polymer mixes with MTZ even at a 30:70 w/w. To explain these observations, comprehensive studies of MTZ-PVP formulations with various contents of both components were performed using Fourier-transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The obtained results clearly showed that the polymer’s topology plays a significant role in the type of interactions occurring between the matrix and MTZ. Additionally, we established that for MTZ-PVP 50:50 and 75:25 w/w BMs, linear polymers have the most substantial impact on inhibiting the crystallization of API. The star-shaped macromolecule turned out to be the least effective in stabilizing amorphous MTZ at these polymer concentrations. Nevertheless, long-term structural investigations of the MTZ-starPVP 30:70 w/w system (which is not achievable for linear PVPs) demonstrated its complete amorphousness for over one month.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Impact of Various Poly(vinylpyrrolidone) Polymers on the Crystallization Process of Metronidazole

Orszulak,

Lamrani,

Tarnacka

et al. 2024

Pharmaceutics

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“…From the drug release data illustrated in Figure 8, it can be observed that the release of Met (a) is slightly higher than that of Ceph (b). This can be attributed to the relatively smaller molecular size of Met (C 6 H 9 N 3 O 3 ) than Ceph (C 16 H 17 N 3 O 4 S), which enables Met to penetrate through the small pore of MOF-5 easily leading to a higher loading and release rate [49].…”

Section: Drug Release Profilementioning

confidence: 99%

Biodegradable Polymer Composites of Metal Organic Framework-5 (MOF-5) for the Efficient and Sustained Delivery of Cephalexin and Metronidazole

Anim,

Mahmoud,

Kelly

et al. 2023

Applied Sciences

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The sustained and controlled delivery of antimicrobial drugs has been largely studied using nanomaterials, like metal organic frameworks (MOFs), and various polymers. However, not much attention has been given to combining MOFs and biodegradable polymers towards the potentially more sustained release of active pharmaceutical ingredients. Herein, we report a comparative study of two widely used antimicrobial drugs, cephalexin and metronidazole, from zinc-based MOF-5 incorporated into biodegradable polycaprolactone (PCL) and poly-lactic glycolic acid (PLGA) composites. Cephalexin and metronidazole were separately loaded into MOF-5 post-synthetically, followed by their integration into biodegradable PLGA and PCL composites. The pristine MOF-5 and the loaded MOFs were thoroughly characterised using Fourier-transformed infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Ultraviolet-visible (UV-Vis) spectroscopy studies were carried out to assess the release of the drugs in PBS for up to 72 h, showing a cumulative release of 24.95 wt% and 27.84 wt% for cephalexin and metronidazole, respectively. The antibacterial properties of the pristine MOF, pure drugs, drug-loaded MOFs and the loaded composites were assessed against Gram-positive and Gram-negative bacterial strains, Staphylococcus aureus or Staphylococcus epidermidis and Escherichia coli or Acinetobacter baumanii, respectively. A cephalexin-loaded MOF-5 composite of PCL (PCL-ceph@MOF-5) showed the best efficiency for the controlled release of drugs to inhibit the growth of the bacteria compared to the other composites. This study demonstrates that the combination of MOFs with biodegradable polymers can provide an efficient platform for the sustained release of antimicrobial drugs and can be a promising tool to manage antimicrobial resistance (AMR).

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“…Considering that drug degradation occurs in several stages via different pathways generating degradation products with adverse bioactivity and increased toxicity, the pharmaceutical field focused efforts in expanding numerous strategies for improving the API stability. Several studies have emerged in this context, reporting the potential use of cyclodextrins (CDs) for improving the stability through the formation of inclusion complexes, which encapsulates labile moieties of the drug molecules [ 8 , 9 , 10 , 11 ]. Among the CDs, β-cyclodextrin (β-CD) is widely used due to its numerous advantages, including a suitable cavity size for the inclusion of guest molecules, its non-toxicity, its biodegradability, and its reasonable price [ 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical Systems as a Strategy to Enhance the Stability of Oxytetracycline Hydrochloride Polymorphs in Solution

2023

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In order to improve the stability of oxytetracycline hydrochloride, a polymorphic antibiotic set of novel binary systems were developed using β-cyclodextrin and amino acids with different acid-basic characteristics as ligands. The formation constants for each system containing β-cyclodextrin, L-aspartic acid, histidine and N-acetylcysteine were determined by Scott’s method and statistical studies. The structure of the binary systems with β-cyclodextrin and N-acetylcysteine was elucidated by NMR experiments. The effect β-cyclodextrin and N-acetylcysteine on the polymorph’s chemical stability in aqueous and phosphate buffered saline solutions at 25 °C was monitored by an optimized and validated high-performance liquid chromatography method. The combination of N-acetylcysteine with the three polymorphs and the β-cyclodextrin system obtained with the form III demonstrated a reduction in the degradation rate of oxytetracycline hydrochloride in the aqueous solution when compared to each free form, with an increase of 20 h in the half time. It evidences that the use of amino acids as ligands constitutes an interesting alternative for pharmaceutical areas. In conclusion, based on the results obtained, these pharmaceutical systems could be candidates for the development of a pharmaceutical formulation for the administration of the drug through reconstituted solutions using the binary system as a promising tool for improving the stability of oxytetracycline hydrochloride polymorphs in solution.

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The impact of the size of acetylated cyclodextrin on the stability of amorphous metronidazole

Cited by 4 publications

References 32 publications

The Impact of Various Poly(vinylpyrrolidone) Polymers on the Crystallization Process of Metronidazole

The Impact of Various Poly(vinylpyrrolidone) Polymers on the Crystallization Process of Metronidazole

Biodegradable Polymer Composites of Metal Organic Framework-5 (MOF-5) for the Efficient and Sustained Delivery of Cephalexin and Metronidazole

Pharmaceutical Systems as a Strategy to Enhance the Stability of Oxytetracycline Hydrochloride Polymorphs in Solution

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