Iterative mathematical approach for understanding deagglomeration behaviour of micronized cohesive powder in formulations

I Parisini, S Hakim, D Murnane

Understanding deagglomeration of cohesive particles is a key component in formulating dry powder inhalers. Coarse carriers are added as diluents and to aid powder handling, and the addition of fine carrier fractions aid the aerosolization of cohesive drug particles. However, this leads to different deagglomeration mechanisms upon aerosolization. The aim of the project was to suggest an appropriate mathematical approach which defines parameters to characterize aerosolization behaviour of cohesive micronized particles alone and in combination of different grade of lactose. Salbutamol sulphate (SS) and salmeterol xinafoate (SX) were chosen as adhesively and cohesively balanced particles when formulated with lactose carriers, respectively. The drugs were blended separately with either fine lactose (FL), coarse lactose (CL) or combination of both in ratio 1:4:63.5, respectively. Laser diffraction using both dry and liquid dispersion systems was employed to characterize the powder population median particle size (i.e. Dv50) and the % volume of particles below 5 μm. The deagglomeration of micronized materials followed an asymptotic monoexponential relationship analogous to a Johnson-Mehl-Avrami-Kolmogorov equation (with positive asymptote ‘m’ and deagglomeration constant ‘k’). However, when the coarse lactose was added, the relationship fitted a bi-exponential equation showing an easily and a poorly dispersed fraction. For both drugs, the extent of deagglomeration was doubled by the addition of FL to CL (63.76 ± 2.85% and 33.62 ± 1.14% for SS:FL:CL and SS:CL, respectively) and SX:FL:CL showed the highest ease of the deagglomeration (2.61 ± 0.23). Based on the formulation studied, the two approaches could be used to understand the deagglomeration behaviour of cohesive particles in combination with lactose or alone.

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