Effect of processing route on the surface properties of amorphous indomethacin measured by inverse gas chromatography.

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.

Investigating the moisture-induced crystallization kinetics of spray-dried lactose.

Gravimetric water sorption experiments were performed to study the crystallization behavior of amorphous spray-dried lactose over a wide range of temperature and humidity conditions. Experiments performed at 25 degrees C between 48 and 60% relative humidity (RH) showed that the onset time to crystallization increased dramatically with decreasing humidity. At 55% RH and above, crystallization occurred in a single detectable step, while below a two-step process was observed. Experiments performed at 51% RH between 22 and 32 degrees C indicated the induction time to crystallization onset increased with decreasing temperature. Above 25 degrees C at 51% RH, crystallization occurred in one measurable step, while below crystallization occurred in two steps. The constant RH with varying temperature results were modeled to determine the crystallization mechanism. Above 25 degrees C a mechanism consisting of two competing reaction sequences fit the data with a 0.9997 correlation coefficient. Both reaction sequences have two steps: an auto-catalytic first step is followed by a three-dimensional diffusion controlled water loss step.

Determining the critical relative humidity for moisture-induced phase transitions.

A new method to determine the onset relative humidity for a glass transition and crystallization processes in amorphous or partially amorphous materials was developed using dynamic gravimetric vapor sorption (DVS). Water vapor can act as a plasticizing agent in amorphous materials, thus lowering the glass transition temperature below room temperatures. Additional water sorption can lead to a crystallization event below the glass transition temperature. On spray-dried lactose the glass transition RH and crystallization RH values were 30 and 58% at 25 degrees C, respectively. Glass transition and crystallization RH values were also measured at 5, 15, 25, 35, and 45 degrees C on a spray-dried salbutamol sulfate sample. The glass transition RH values for the salbutamol sulfate sample ranged from 64.5% RH (5 degrees C) to 32.8% RH (45 degrees C) while the crystallization RH values ranged from 81.0% RH (5 degrees C) to 50.4% RH (45 degrees C). The results clearly show that the glass transition and crystallization humidity values decrease as the sample temperature increases.

The use of inverse phase gas chromatography to study the change of surface energy of amorphous lactose as a function of relative humidity and the processes of collapse and crystallisation.

The purpose of this study was to assess the effect of relative humidity (RH) on the surface energy of amorphous lactose. Two samples of amorphous lactose were investigated; a spray dried 100% amorphous material and a ball milled sample of crystalline lactose. The milled sample had less than 1% amorphous content by mass, but on investigation at 0% RH, yielded surface energies comparable to those obtained from the 100% amorphous material, indicating that the surface was amorphous. The effect of increasing humidity was to reduce the dispersive surface energy of the two samples from 36.0 +/- 0.14 and 41.6 +/- 1.4 mJ m(-2) at 0% RH for the spray dried and milled samples respectively, to a value comparable to that obtained for the crystalline alpha-lactose monohydrate of 31.3 +/- 0.41 mJ m(-2). The change in surface energy due to water sorption was only reversible up to 20% RH; after exposure to higher RH values subsequent drying did not result in a return to the original surface energy of the amorphous form. This shows that the surface is reorganising as the glass transition temperature (Tg) is reduced, even though the sample has not collapsed or crystallised. It was possible to follow the collapse behaviour in the column with ease, using a number of different methods.

Characterization of Microporous Aluminas by Inverse Gas Chromatography.

Inverse gas chromatography (IGC) is a versatile tool for the characterization of porous solids. IGC at finite dilution has historically been used for isotherm measurements because of fast equilibration times. A combination of IGC with a flash thermodesorption method allows the separation of micropores and outer surface contributions due to different adsorption mechanisms. Whereas the outer surface and the mesopores have a mono-/multilayer sorption mechanism, the micropores are filled according to the "theory of volume filling of micropores" model. Therefore, a higher energy is required for desorption out of micropores than for desorption out of mesopores and from the surface. This difference is used to calculate two separate isotherms respective to each contribution. Four aluminas with different microporosities are investigated to show the benefit of this approach. Copyright 2000 Academic Press.

The use of inverse phase gas chromatography to measure the surface energy of crystalline, amorphous, and recently milled lactose.

PURPOSE: To assess differences in surface energy due to processing induced disorder and to understand whether the disorder dominated the surfaces of particles. METHODS: Inverse gas chromatography was used to compare the surface energies of crystalline, amorphous, and ball milled lactose. RESULTS: The milling process made ca 1% of the lactose amorphous, however the dispersive contribution to surface energy was 31.2, 37.1, and 41.6 mJ m(-2) for crystalline, spray dried and milled lactose, respectively. A physical mixture of crystalline (99%) and amorphous (1%) material had a dispersive surface energy of 31.5 mJ m(-2). CONCLUSION: Milling had made the surface energy similar to that of the amorphous material in a manner that was very different to a physical mixture of the same amorphous content. The milled material will have similar interfacial interactions to the 100% amorphous material.