The nature of crystal disorder in milled pharmaceutical materials

Chamarthy, Sai Prasanth; Pinal, Rodolfo

doi:10.1016/j.colsurfa.2008.06.040

Cited by 79 publications

(70 citation statements)

References 33 publications

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“…[1][2][3] When milling a crystalline active pharmaceutical ingredient (API), the mechanical stress during the milling process cannot only change the particle size, surface area and crystallinity of the API but can also induce polymorphic transformations. [3][4][5][6][7][8][9][10][11] Solid-state polymorphic transitions and amorphization induced by milling have been reported for many pharmaceutical products such as gabapentin, 3 famotidine, 9 ranitidine hydrochloride, 10 and Fananserine. 11 Cryo-milling (Cryogenic grinding) seeks to operate ball milling, a high energy process, at low temperatures with the aid of cryogenic media such as liquid nitrogen.…”

Section: Introductionmentioning

confidence: 99%

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

MacFhionnghaile

Caron

et al. 2013

Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

MacFhionnghaile

Caron

et al. 2013

Journal of Pharmaceutical Sciences

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“…It provides access to several physicochemical (surface and bulk) properties of materials, including their surface energy, phase transitions, solubility parameter, crystallinity, and acid-base characteristics (133,134). It has been also used to detect surface energy changes caused by milling (135). It was found for sucrose that milling does not influence the crystal structure particles, but only the particle size and relative exposure of specific crystal planes.…”

Section: Inverse Gas Cromatographymentioning

confidence: 99%

Methods of amorphization and investigation of the amorphous state

Einfalt¹,

Planinšek²,

Hrovat³

2013

Acta Pharmaceutica

114

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.g., polymorphs) provides pharmaceutical scientists with an opportunity to select the preferred form of the material to be used in a formulation. This is very useful since critical properties, such as particle morphology and dissolution properties, are frequently different in the different physical forms of a material. The amorphous form of pharmacologically active materials has received considerable attention because, in theory, it represents the most energetic solid state of a material, and should thus provide the biggest advantages in terms of dissolution rate and bioavailability (1). However, the amorphous form also shows various disadvantages, such as lower physical stability compared to crystals.The structure of an amorphous solid is usually described as possessing a crystal--like short-range molecular arrangement, but lacking a long-range order. As illustrated by Fig. 1, the immediate environment of a molecule (m) in an amorphous solid may not differ significantly from that in a crystal (e.g., similar number of and distance to nearest neighbors), but an amorphous solid lacks any long-range transational-orientational symmetry that characterizes a crystal (1). However, this is only true when we are dealing The amorphous form of pharmaceutical materials represents the most energetic solid state of a material. It provides advantages in terms of dissolution rate and bioavailability. This review presents the methods of solid--state amorphization described in literature (supercooling of liquids, milling, lyophilization, spray drying, dehydration of crystalline hydrates), with the emphasis on milling. Furthermore, we describe how amorphous state of pharmaceuticals differ depending on the method of preparation and how these differences can be screened by a variety of spectroscopic (X-ray powder diffraction, solid state nuclear magnetic resonance, atomic pairwise distribution, infrared spectroscopy, terahertz spectroscopy) and calorimetry methods.

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“…Finite concentration IGC experiments on needle-shaped D-mannitol crystals indicated that crystal fracture was dominated by geometric factors and not by the weakest attachment energy (10). Finally, IGC studies by Chamarthy and Pinal (11) revealed that the surface energy values of cryomilled samples were higher than those of the crystalline and amorphous (quench melt) counterparts for both felodipine and griseofulvin.…”

Section: Introductionmentioning

confidence: 93%

Effect of Processing Route on the Surface Properties of Amorphous Indomethacin Measured by Inverse Gas Chromatography

et al. 2012

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Abstract. The aim of this study was to investigate the effect of processing route (i.e., quench cooling and ball milling) on the surface energy heterogeneity and surface chemistry of indomethacin (IMC). Recently developed inverse gas chromatography (IGC) methodology at finite concentrations was employed to determine the surface energy distributions of crystalline, quench cooled and milled IMC samples. Surface properties of crystalline and processed IMC were measurably different as determined by the IGC and other conventional characterization techniques: differential scanning calorimetry and powder X-ray diffraction. Quench cooled IMC was in fully amorphous form. Milled IMC showed no amorphous character by calorimetric or X-ray diffraction studies. It was demonstrated that both processed IMC samples were energetically more active than the crystalline IMC. In particular, milled IMC exhibited a relatively higher dispersive surface energy and higher surface basicity (electron donor capability). This may be attributed to the creation of surface defect sites or exposure of higher energy crystal facets during the milling process. This study confirms that processing route has notable influence on the surface energy distribution and surface acid-base character. IGC was demonstrated as a powerful technique for investigating surface properties of real-world, heterogeneous pharmaceutical materials.

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The nature of crystal disorder in milled pharmaceutical materials

Cited by 79 publications

References 33 publications

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

Formation, Physical Stability, and Quantification of Process-Induced Disorder in Cryomilled Samples of a Model Polymorphic Drug

Methods of amorphization and investigation of the amorphous state

Effect of Processing Route on the Surface Properties of Amorphous Indomethacin Measured by Inverse Gas Chromatography

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