Effect of milling on the plastic and the elastic stiffness of lactose particles.

The purpose of this study was to investigate the effect of degree of disorder of a series of α-lactose monohydrate powders, prepared by milling for different time periods, on the plastic and the elastic stiffness of the particles. As references, a series of physical mixtures consisting of original crystalline particles and amorphous particles obtained by spray-drying was used. In addition, the effect of powder pre-storage humidity on the mechanical properties was investigated.

Comminution-amorphisation relationships during ball milling of lactose at different milling conditions.

The purpose of the study was to investigate the relationship between comminution and amorphisation of α-lactose monohydrate particles during ball milling under different milling conditions, including ball-to-powder mass ratio, milling time and ball diameter. The results revealed that at a constant ball filling ratio, ball-to-powder mass ratio of 25:1 resulted in the lowest minimum particle diameter of ∼5μm and the highest degree of apparent amorphous content of 82%. The rate of comminution was high during early stage of milling whereas the degree of apparent amorphous content increased gradually at a slow rate.

Considerations on the quantitative analysis of apparent amorphicity of milled lactose by Raman spectroscopy.

The main purpose of the study was to evaluate various pre-processing and quantification approaches of Raman spectrum to quantify low level of amorphous content in milled lactose powder. To improve the quantification analysis, several spectral pre-processing methods were used to adjust background effects. The effects of spectral noise on the variation of determined amorphous content were also investigated theoretically by propagation of error analysis and were compared to the experimentally obtained values.

Mechanism of amorphisation of micro-particles of griseofulvin during powder flow in a mixer.

The purpose of the research was to investigate the degree of solid-state amorphisation during powder flow and to propose a mechanism for this transformation. Micro-particles of griseofulvin (about 2 μm in diameter) were mixed in a shear mixer under different conditions to influence the inter-particulate collisions during flow, and the degree of amorphisation was determined by micro-calorimeter. The amorphisation of griseofulvin particles (GPs) during repeated compaction was also determined.

The influence of PVP incorporation on moisture-induced surface crystallization of amorphous spray-dried lactose particles.

We have recently shown that atomic force microscopy (AFM) may be an appropriate method for characterisation of the re-crystallization of amorphous particles. In this study, spray-dried composite particles consisting of lactose and polyvinyl pyrrolidon (PVP) were characterised by AFM and electron spectroscopy for chemical analysis (ESCA), and their response on increasing the relative humidity (RH) was investigated. The PVP content in the particles used was 0, 5 or 25 wt.

Compression behaviour and tablet-forming ability of spray-dried amorphous composite particles.

The aim of this study was to investigate the compression behaviour and tablet-forming ability of spray-dried amorphous two- and three-component composite particles. Particles of lactose alone, two-component particles of lactose and PVP, and three-component particles of lactose, PVP and a small amount of polysorbate 80 were prepared by spray-drying. Two qualities of PVP with different molecular weights were used for the preparation of both types of particles.

Long-term stabilisation potential of poly(vinylpyrrolidone) for amorphous lactose in spray-dried composites.

The aim of this study was to investigate the potential of poly(vinylpyrrolidone) (PVP) to inhibit the crystallisation of amorphous lactose during storage of the composites up to 6 months. Short-term stability was assessed by microcalorimetry over 10 days and long-term stability by storage in desiccators with different relative humidities for 3 and 6 months. The solid-state structure of the particles after storage was analysed by differential scanning calorimetry.

Moisture-induced surface crystallization of spray-dried amorphous lactose particles studied by atomic force microscopy.

The aim of this study was to show that atomic force microscopy (AFM) can be used to obtain mechanistic and kinetic information about the process of moisture-induced surface crystallization of single particles of amorphous lactose. Completely amorphous lactose particles were prepared by spray-drying a solution of alpha-lactose monohydrate, and moisture-induced crystallization was monitored for a bed of particles by microcalorimetry and for single particles by AFM. From the AFM images it was found that crystallization of the surface of single particles can be described in terms of a sequence of three events: an initial smoothening of the surface, formation of crystalline nanostructures dispersed in amorphous material, and growth of these structures to a complete crystalline surface.

Effect of polymer content and molecular weight on the morphology and heat- and moisture-induced transformations of spray-dried composite particles of amorphous lactose and poly(vinylpyrrolidone).

Purpose: The aim was to investigate the influence of polymer content and molecular weight on the morphology and heat- and moisture-induced transformations, as indicators of stability, of spray-dried composite particles of amorphous lactose and poly(vinylpyrrolidone) (PVP).

Methods: Amorphous lactose and composite particles of amorphous lactose with different contents and molecular weights of PVP were prepared by spray drying. The nanostructure of the particles was analyzed by x-ray powder diffractometry, the morphology by light microscopy and SEM, the glass transition temperatures (Tg), crystallization temperatures (Tc), heats of crystallization and melting temperatures by differential scanning calorimetry, and moisture-induced crystallizations gravimetrically and by microcalorimetry.