Adhesion forces in interactive mixtures for dry powder inhalers--evaluation of a new measuring method.

Dry powder inhalers mostly contain carrier based formulations where micronized drug particles are adhered to coarse carrier particles. The performance of the dry powder inhaler depends on the inhaler device, the inhalation manoeuvre and the formulation. The most important factor influencing the behaviour of the formulation is the adhesion force acting between the active ingredient and the carrier particles, which can be measured using different methods, for example the centrifuge technique or atomic force microscopy. In this study the tensile strength method, usually applied to determine cohesion forces between powder particles of one material, is optimized for adhesion force measurements between powder particles of unlike materials. Adhesion force measurements between the carrier materials lactose or mannitol and the drug substance salbutamol sulphate using the tensile strength method and the atomic force microscopy show higher values with increasing relative humidity. Consequently, the fine particle fraction determined using the Next Generation Impactor decreases with increasing relative humidity as a result of the enhanced interparticle interactions.

Solid dispersions of nimodipine and polyethylene glycol 2000: dissolution properties and physico-chemical characterisation.

The incorporation of a drug in a carrier by melt embedding may either result in a solid solution or in a solid suspension of the active ingredient within the carrier material. As the dispersivity of the drug is of outstanding importance for its dissolution characteristics, parameters which are supposed to influence crystallinity and dispersivity, e.g. cooling rate during preparation and storage conditions like temperature and relative humidity are investigated. It is found that the absence of crystalline drug material in solid dispersions containing nimodipine and polyethylene glycol 2000 is the prerequisite for a high dissolution rate and a remarkable supersaturation in the dissolution medium. Shock freezing during the preparation process, low storage temperatures and low relative humidities are identified to prevent recrystallisation. Furthermore, emphasis is put on the physico-chemical characterisation of solid dispersions. It is shown that the determination of crystallinity and dispersivity of the drug in solid dispersions can only be successful by combining different investigation methods like differential scanning calorimetry, hot stage microscopy, X-ray diffraction as well as macroscopic observation.