Assessment of milling-induced disorder of two pharmaceutical compounds.

The goal of this study was to provide a better framework for understanding the bulk and surface disorder in milled crystalline materials. The surface and bulk properties of two model compounds, ketoconazole and griseofulvin, were characterized by inverse gas chromatography as a function of cryomilling time. Cryomilling was used to decrease the effect of temperature-induced changes, which commonly occur during milling. A reduction in crystallinity was observed for both compounds by powder X-ray diffraction and differential scanning calorimetry (DSC). Particle size analysis revealed a continued mode of attrition for griseofulvin, whereas attrition followed by growth was observed for ketoconazole. An increase in surface energy for both compounds was noticed upon initial milling, followed by a decrease as milling time continued. A determination and comparison of the surface phase transformations using chromatographic methods and DSC was carried out. Both ketoconazole and griseofulvin showed an earlier phase transformation relative to DSC. It is proposed that an intermediate metastable state for griseofulvin and a change in the surface structure of ketoconazole is the consequence of the cryomilling process.

[1]  J. Booth,et al.  Determining the critical relative humidity for moisture-induced phase transitions. , 2004, International journal of pharmaceutics.

[2]  A. Godec,et al.  Structural evolution of indomethacin particles upon milling: time-resolved quantification and localization of disordered structure studied by IGC and DSC. , 2010, Journal of pharmaceutical sciences.

[3]  W. Johnson,et al.  Structural and thermodynamic properties of heavily mechanically deformed Ru and AlRu , 1989 .

[4]  T. Hamieh,et al.  New approach to characterise physicochemical properties of solid substrates by inverse gas chromatography at infinite dilution. II. Study of the transition temperatures of poly(methyl methacrylate) at various tacticities and of poly(methyl methacrylate) adsorbed on alumina and silica. , 2002, Journal of chromatography. A.

[5]  Exploratory experiments on kinetics of comminution , 1970 .

[6]  R. Suryanarayanan,et al.  Determination of Glass Transition Temperature and in Situ Study of the Plasticizing Effect of Water by Inverse Gas Chromatography , 2003, Pharmaceutical Research.

[7]  Interpretation of the differences in the surface energetics of two optical forms of mannitol by inverse gas chromatography and molecular modelling. , 1999, International journal of pharmaceutics.

[8]  R. Pinal,et al.  The nature of crystal disorder in milled pharmaceutical materials , 2008 .

[9]  N. Rasenack,et al.  Dissolution Rate Enhancement by in Situ Micronization of Poorly Water-Soluble Drugs , 2002, Pharmaceutical Research.

[10]  J. Watts,et al.  Determination of surface heterogeneity of D-mannitol by sessile drop contact angle and finite concentration inverse gas chromatography. , 2010, International journal of pharmaceutics.

[11]  C. Caramella,et al.  The effect of milling and addition of dry binder on the interparticulate bonding mechanisms in sodium chloride tablets , 1998 .

[12]  G. Buckton,et al.  Inverse Gas Chromatography: Investigating Whether the Technique Preferentially Probes High Energy Sites for Mixtures of Crystalline and Amorphous Lactose , 2004, Pharmaceutical Research.

[13]  R. Pinal,et al.  Process induced disorder in crystalline materials: differentiating defective crystals from the amorphous form of griseofulvin. , 2008, Journal of pharmaceutical sciences.

[14]  L. Lavielle,et al.  The Role of the Interface in Carbon Fibre-Epoxy Composites , 1987 .

[15]  C. Nyström,et al.  Physicochemical aspects of drug release. VIII. The relation between particle size and surface specific dissolution rate in agitated suspensions , 1988 .

[16]  G. Alderborn,et al.  Increased metastable solubility of milled griseofulvin, depending on the formation of a disordered surface structure , 1994 .

[17]  G. Vancso,et al.  Characterization of Glass Transition Temperature and Surface Energy of Bituminous Binders by Inverse Gas Chromatography , 2004 .

[18]  Graham Buckton,et al.  Determination of the changes in surface energetics of cefditoren pivoxil as a consequence of processing induced disorder and equilibration to different relative humidities. , 2004, International journal of pharmaceutics.

[19]  P. York,et al.  Determination of the surface properties of two batches of salbutamol sulphate by inverse gas chromatography , 1994 .

[20]  P. York,et al.  Characterisation of the surface energetics of milled dl-propranolol hydrochloride using inverse gas chromatography and molecular modelling , 1998 .

[21]  P Augustijns,et al.  Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[22]  S. Sartnurak,et al.  The impact of low levels of amorphous material (<5%) on the blending characteristics of a direct compression formulation. , 2002, International journal of pharmaceutics.

[23]  P. Young,et al.  On the physical transformations of processed pharmaceutical solids. , 2005, Micron.

[24]  Jerry Y. Y. Heng,et al.  The Effects of Milling on the Surface Properties of Form I Paracetamol Crystals , 2006, Pharmaceutical Research.

[25]  P. York,et al.  Determination of surface properties and flow characteristics of salbutamol sulphate, before and after micronisation , 1998 .