The effect of particle size and concentration on the adhesive characteristics of a model drug-carrier interactive system

Abstract

The effect of concentration and particle size on the adhesive tendency of drug particles in a model interactive system was investigated using a centrifuge technique. The model interactive system consisted of drug powders adhered to coated glass carrier beads. Adhesion profiles of per cent of drug remaining on the carrier versus the square of the speed of rotation were a logarithmic normal function. Increase in the adherent particle size and concentration decreased the adhesive tendency of all drug powders studied. Particle collisions during detachment and the formation of multiparticulate layers even before the monolayer saturation of the carrier surface were responsible for the reduced adhesive stability of the drugs on the carrier as the particle loading increased.

The Mode of Drug Particle Detachment from Carrier Crystals in an Air Classifier-Based Inhaler

“…On the other hand, the X 90 -value for the coarsest fraction is 24.68 m. This is considerably higher than even the X 100 -value of the primary drug particles from RODOS dispersion at 5 bar (9 m). This confirms that drug particle agglomeration has occurred on the carrier surface (2). The results also show that the degree of agglomeration depends on the carrier particle mass.…”

“…Therefore, saturation of these irregularities results in a higher effectivity of the press-on forces, which has the effect of a higher mean adhesive force with increasing carrier payload for mixtures with coarse carrier particles. As already discussed in the introduction a high carrier payload could also promote drug particle agglomeration on the carrier surface (1,2,4). This increases the mass of the particles to be detached and by that the removal force (F R ).…”

“…Very little has been reported in this respect. It has been described that drug particles tend to form particle agglomerates (layers) on the carrier crystals at concentrations well below that for a monolayer on the carrier surface (2). Strong clusters are formed that can be dislodged from the carrier as a whole.…”

The Rate of Drug Particle Detachment from Carrier Crystals in an Air Classifier-Based Inhaler

“…A decreasing F R at a constant inspiratory flow rate occurs only when the mass of subsequently detached particles becomes less (e.g., when large primary particles and/ or agglomerates are dislodged first and smaller primary particles next). This may be possible, because it has been described that drug particles tend to form particle agglomerates on the carrier crystals, even at drug concentrations well below that for a monolayer on the carrier surface (30). An increasing F A with increasing number of particles already separated from the carrier could have different reasons, depending on the initial carrier payload and the size and effectivity of presson forces during the mixing process (7).…”

Micronized Drug Adhesion and Detachment from Surfaces: Effect of Loading Conditions

“…Thus it could be seen that the forces of drug loading on to the film surface affect the aerosol characteristics of the drug dispersions. These forces are responsible for drug aggregation on the lactose carrier surface (Kulvanich and Stewart 1987;de Boer et al 2004a). This aggregation increases the magnitude of the removal forces acting on such particles during inhalation (Louey and Stewart 2002) and the degree of aggregation might affect the FPF (de Boer et al 2004a(de Boer et al , 2004bPodczeck 1998b).…”