The purpose of the present study was to investigate the possibility of improving the dissolution properties of glisentide, a poorly water-soluble antidiabetic drug, by grinding in a high energy micromill, alone or in mixture with polyvinylpyrrolidone (PVP). Conventional and modulated differential scanning calorimetry (DSC, MDSC), thermogravimetry (TGA), X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), hot-stage FT-IR thermomicroscopy and scanning electron microscopy (SEM) were used to characterize the drug solid state, whereas its dissolution rates were determined according to the dispersed amount method. The techniques utilized enabled exclusion of polymorphism phenomena as a consequence of mechanical treatment, and revealed a progressive drug amorphization during grinding. In particular, MDSC allowed a clear determination of the glass transition temperature of the amorphous drug, enabling separation of glass transition from enthalpic relaxation. The amorphous state of the ground drug was the main responsible factor for the obtained 100% dissolution efficiency increase in comparison with the untreated drug. Further significant increases in dissolution properties, directly related to the polymer content in the mixture, were obtained by co-grinding with PVP, whose presence clearly favored drug amorphization, allowing a strong reduction of time and frequency of grinding necessary for obtaining complete drug amorphization.

INVESTIGATION OF THE EFFECTS OF GRINDING AND CO-GRINDING ON PHYSISCOCHEMICAL PROPERTIES OF GLISENTIDE / P. Mura; M. Cirri; M.T. Faucci; J.M. Ginès-Dorado; G.P. Bettinetti. - In: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS. - ISSN 0731-7085. - ELETTRONICO. - 30:(2002), pp. 227-237. [10.1016/S0731-7085(02)00252-2]

INVESTIGATION OF THE EFFECTS OF GRINDING AND CO-GRINDING ON PHYSISCOCHEMICAL PROPERTIES OF GLISENTIDE

MURA, PAOLA ANGELA;CIRRI, MARZIA;
2002

Abstract

The purpose of the present study was to investigate the possibility of improving the dissolution properties of glisentide, a poorly water-soluble antidiabetic drug, by grinding in a high energy micromill, alone or in mixture with polyvinylpyrrolidone (PVP). Conventional and modulated differential scanning calorimetry (DSC, MDSC), thermogravimetry (TGA), X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), hot-stage FT-IR thermomicroscopy and scanning electron microscopy (SEM) were used to characterize the drug solid state, whereas its dissolution rates were determined according to the dispersed amount method. The techniques utilized enabled exclusion of polymorphism phenomena as a consequence of mechanical treatment, and revealed a progressive drug amorphization during grinding. In particular, MDSC allowed a clear determination of the glass transition temperature of the amorphous drug, enabling separation of glass transition from enthalpic relaxation. The amorphous state of the ground drug was the main responsible factor for the obtained 100% dissolution efficiency increase in comparison with the untreated drug. Further significant increases in dissolution properties, directly related to the polymer content in the mixture, were obtained by co-grinding with PVP, whose presence clearly favored drug amorphization, allowing a strong reduction of time and frequency of grinding necessary for obtaining complete drug amorphization.
2002
30
227
237
P. Mura; M. Cirri; M.T. Faucci; J.M. Ginès-Dorado; G.P. Bettinetti
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/3989
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