β-Cyclodextrin complexation as an effective drug delivery system for meropenem

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• 作者：Magdalena Paczkowska^a ; Mikołaj Mizera^a ; Daria Szymanowska-Powałowska^b ; Kornelia Lewandowska^c ; Wioletta Błaszczak^d ; Joanna Gościańska^e ; Robert Pietrzak^e ; Judyta Cielecka-Piontek^a ; ^{jpiontek@ump.edu.pl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DPH-I ; dehydropeptidase-I ; MER-β-CD ; meropenem-β-cyclodextrin inclusion complex ; β-CD ; β-cyclodextrin ; MER ; meropenem ; UHPLC ; Ultra High-Performance Liquid Chromatography ; HPLC ; High-Performance Liquid Chromatography ; FT-IR ; Fourier Transform Infrared Spectroscopy ; DSC ; differential scanning calorimetry ; DFT ; Density Functional Theory ; MMFF94 ; Merck Molecular Force Field 94 ; PM6 ; Parameterization Method 6 ; T ; temperature ; RH ; Relative Humidity ; UV&ndash ; VIS ; Ultraviolet&ndash ; Visible Spectrophot
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：99
• 期：Complete
• 页码：24-34
• 全文大小：2328 K

文摘

Following the preparation of an inclusion complex of β-cyclodextrin and meropenem, methods based on FT-IR, Raman and DSC were used for its characterization. An analysis of changes in the stability of meropenem after complexation showed that the complex may serve as a valuable delivery system significantly contributing to enhanced meropenem stability in aqueous solutions and in the solid phase. Due to a sustained transfer of meropenem from the cavity of the cyclodextrin it was possible to maintain a constant desired meropenem concentration over a period of 20 h, as confirmed by a release study. An evaluation of microbial activity not only demonstrated that the bactericidal action of meropenem was not stopped as a result of complexation but even pointed to greater growth inhibition in certain clinically important strains. The fact that investigations of meropenem stability and microbial activity proposed the carbonyl groups as those domains of a meropenem molecule that are instrumental in the formation of a complex with β-cyclodextrin supports the findings of theoretical studies based on molecular modeling.