Nanostructured Micronized Solid Dispersion of Crystalline-Amorphous Metronidazole Embedded in Amorphous Polymer Matrix Prepared by Nano Spray Drying

Mirankó, Mirella and Trif, László and Tóth, Judit and Feczkó, Tivadar (2021) Nanostructured Micronized Solid Dispersion of Crystalline-Amorphous Metronidazole Embedded in Amorphous Polymer Matrix Prepared by Nano Spray Drying. ADVANCED POWDER TECHNOLOGY : INTERNATIONAL JOURNAL OF SCIENCE AND TECHNOLOGY OF POWDER AND PARTICULATE MATERIALS. pp. 1-45. ISSN 0921-8831 (print); 1568-5527 (online)

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Abstract

In this study metronidazole drug was encapsulated by hydroxypropyl methylcellulose and polyvinylpyrrolidone polymers from solutions using nano spray drying technology. The influence of the process parameters and formulation variables were investigated on product morhology and structure, production yield and entrapment efficiency. The use of surface active admixtures (polyvinyl alcohol, Tween80 and Pluronic F68) increased the product yield substantially. The entrapped metronidazole was partially in crystalline and amorphous state in both amorphous polymers as confirmed by DSC and powder X-ray diffraction measurements. In the composites with hydroxypropyl methylcellulose the degree of crystallinity was between 50.2 and 81.0 %, and with polyvinylpyrrolidone between 35.0 and 50.0 % (with respect to the drug content). Melting point decrease phenomena was observed by differential scanning calorimetry between bulk metronidazole and spray dried products. Peak broadening was indicated by powder X-ray diffraction measurements, which could be the result of formation of small drug crystallites. The TEM images showed beside the larger crystals (200–400 nm) a fraction of smaller crystals (20–50 nm in diameter), which are in good correlation with the nt scattering domain sizes of 19–87 nm based on X-ray data. The drug-polymer composites produced by nano spray drying process were identified as crystalline-amorphous nanostructured micronized solid dispersions.

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