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 microm), 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 h(EFF) that is constant with respect to particle size. However, for particles in the so called "small" size regime (d less than about 50 microm), 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 h(EFF) approximately equal to the particle radius or diameter. This paper presents the first experimental determination of h(EFF) for particles less than about 2 microm. The powder dissolution kinetics of six suspensions over the particle diameter range of 5.9 +/- 0.1 to 0.53 +/- 0.05 microm are analyzed to yield h(EFF) values of 8.5 +/- 1.9 to 0.34 +/- 0.14 microm. The theoretical expectation for mass transport, dissolution time proportional to d(2.0), is in good agreement with the experimental results of dissolution time proportional to d(2.3). An understanding of these mass transfer mechanisms allows pharmaceutical scientists to achieve targeted release rates with minimum ensemble instability.