Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25.

The glass forming properties of ketoconazole were investigated using differential scanning calorimetry (DSC), by quench cooling liquid ketoconazole from T(m)+10 to 273.1 K, followed by subsequent heating at 5 K/min to T(m)+10 K. It was shown that liquid ketoconazole forms a glass which did not recrystallise following reheating, indicating its stability; T(g) was found to be 317.5+/-0.3 K. However, the presence of a small amount of crystalline ketoconazole was able to convert the amorphous drug back to the crystalline state: the addition of only 4.1% (w/w) of crystalline material converted 77.1% of the glass back to the crystalline state, and this value increased as the amount of added crystals increased. PVP K25 was found to be highly effective in the prevention of such recrystallisation, but only if the amorphous drug was formulated in a solid dispersion, since physical mixing of amorphous ketoconazole with the polymer resulted in recrystallisation of the former compound. Storage of the solid dispersions for 30 days at 298.1 K (both 0 and 52% RH) in the presence or absence of crystals did not result in recrystallisation of the amorphous drug. Solid dispersions formed compatible blends as one single T(g) was observed, which gradually increased with increasing amounts of PVP K25, indicating the anti-plasticising property of the polymer. The values of T(g) followed the Gordon-Taylor equation, indicating no significant deviation from ideality and suggesting the absence of strong and specific drug-polymer interactions, which was further confirmed with 13C NMR and FT-IR. It can be concluded therefore that the physical mechanism of the protective effect is not caused by drug-polymer interactions but due to the polymer anti-plasticising effect, thereby increasing the viscosity of the binary system and decreasing the diffusion of drug molecules necessary to form a lattice.

In-house packing and testing of capillaries for capillary electrochromatography using simple equipment.

The feasibility of producing packed capillaries for capillary electrochromatography (CEC) is evaluated. Emphasis is put on the fact that only material was used that is already available in any LC/CE orientated laboratory. An experimental set-up is developed for filling the capillaries by use of an ordinary LC pump, and frits are sintered with a glowing resistance wire, fed by a d.c. power supply. Electrochromatography was carried out in an in-house built capillary electrophoresis apparatus, without pressurizing the vials. Under these conditions, the capillaries performed well, producing up to 190,000 plates per meter. Bubble formation did not appear, on condition that the mobile phase was thoroughly helium degassed. Even at ambient temperature, electrophoresis obeyed Ohm's law up to a voltage of 30 kV, proving that Joule heating was not a major concern.