General solution for diffusion-controlled dissolution of spherical particles. 1. Theory.

Three classical particle dissolution rate expressions are commonly used to interpret particle dissolution rate phenomena. Our analysis shows that an assumption used in the derivation of the traditional cube-root law may not be accurate under all conditions for diffusion-controlled particle dissolution. Mathematical analysis shows that the three classical particle dissolution rate expressions are approximate solutions to a general diffusion layer model. The cube-root law is most appropriate when particle size is much larger than the diffusion layer thickness, the two-thirds-root expression applies when the particle size is much smaller than the diffusion layer thickness. The square-root expression is intermediate between these two models. A general solution to the diffusion layer model for monodispersed spherical particles dissolution was derived for sink and nonsink conditions. Constant diffusion layer thickness was assumed in the derivation. Simulated dissolution data showed that the ratio between particle size and diffusion layer thickness (a0/h) is an important factor in controlling the shape of particle dissolution profiles. A new semiempirical general particle dissolution equation is also discussed which encompasses the three classical particle dissolution expressions. The success of the general equation in explaining limitations of traditional particle dissolution expressions demonstrates the usefulness of the general diffusion layer model.

[1]  G. Milosovich,et al.  Dissolution rate studies. II. Dissolution of particles under conditions of rapid agitation. , 1963, Journal of pharmaceutical sciences.

[2]  W. Higuchi,et al.  Dissolution rates of finely divided drug powders. I. Effect of a distribution of particle sizes in a diffusion-controlled process. , 1963, Journal of pharmaceutical sciences.

[3]  A. W. Hixson,et al.  Dependence of Reaction Velocity upon surface and Agitation , 1931 .

[4]  W. Higuchi,et al.  Dissolution rates of finely divided drug powders. II. Micronized methyl-prednisolone. , 1963, Journal of pharmaceutical sciences.

[5]  P. Harriott Mass transfer to particles: Part I. Suspended in agitated tanks , 1962 .

[6]  C. Nyström,et al.  Physicochemical aspects of drug release. VIII. The relation between particle size and surface specific dissolution rate in agitated suspensions , 1988 .

[7]  C. Nyström,et al.  Physicochemical aspects of drug release: X. Investigation of the applicability of the cube root law for characterization of the dissolution rate of fine particulate materials , 1990 .

[8]  C. Nyström,et al.  Physicochemical aspects of drug release. VII. The effect of surfactant concentration and drug particle size on solubility and dissolution rate of felodipine, a sparingly soluble drug , 1988 .

[9]  W. Nernst,et al.  Theorie der Reaktionsgeschwindigkeit in heterogenen Systemen , 1904 .

[10]  A. Noyes,et al.  The rate of solution of solid substances in their own solutions , 1897 .

[11]  Erich Brunner,et al.  Reaktionsgeschwindigkeit in heterogenen Systemen , 1904 .

[12]  M. Figueiredo,et al.  Modeling dissolution of sparingly soluble multisized powders. , 1997, Journal of pharmaceutical sciences.

[13]  P V Pedersen,et al.  Experimental evaluation of three single-particle dissolution models. , 1976, Journal of pharmaceutical sciences.