Experimental determination of the diffusion boundary layer width of micron and submicron particles

Powder dissolution kinetics have shown that for particles in the so called “large” size regime (more than about 50 μm), the dissolution rate scales as the specific surface area, i.e. rate proportional to d−1 where d is the particle diameter. This is consistent with an effective diffusion boundary layer width hEFF that is constant with respect to particle size. However, for particles in the so called “small” size regime (d less than about 50 μm), the dissolution rate has a stronger dependence than proportional to d−1 [Bisrat, M., Anderberg, E.K., Barnett, M.I., Nystroem, C., 1992. Physicochemical aspects of drug release. XV. Investigation of diffusional transport in dissolution of suspended, sparingly soluble drugs. Int. J. Pharm., 80, 191–201; Mosharraf, M., Nystroem, C., 1995. The effect of particle size and shape on the surface specific dissolution rate of microsized practically insoluble drugs. Int. J. Pharm., 122, 35–47]. In this regime, Prandtl boundary layer theory predicts an hEFF approximately equal to the particle radius or diameter. This paper presents the first experimental determination of hEFF for particles less than about 2 μm. The powder dissolution kinetics of six suspensions over the particle diameter range of 5.9 ± 0.1 to 0.53 ± 0.05 μm are analyzed to yield hEFF values of 8.5 ± 1.9 to 0.34 ± 0.14 μm. The theoretical expectation for mass transport, dissolution time proportional to d2.0, is in good agreement with the experimental results of dissolution time proportional to d2.3. An understanding of these mass transfer mechanisms allows pharmaceutical scientists to achieve targeted release rates with minimum ensemble instability.