Effects of particle size, surface nature and crystal type on dissolution rate

Abstract

Solid drug delivery systems are crucial formulations for the oral route. In such systems, particle size and polymorphism have a strong impact on drug dissolution and on drug absorption. Starting from the role of particle size in dissolution rate, the Noyes-Whitney equation, the modified form by Nernst-Brunner and the cube root equation are here described. According to these equations diffusion of a solute through a boundary layer around the particles is the rate limiting step for both drug dissolution and absorption and, thus, depends on the specific (external) surface area of the particles, the diffusion coefficient of the dissolved drug, the thickness of the boundary layer and the drug solubility. In relation to this, good wetting of the particle surface by the surrounding liquid and adequate particle dispersion play an essential role. Information from dissolution rates suggests that the thickness of the boundary layer is constant for larger particle sizes, but dependent upon size for smaller particles. Given the larger surface area of smaller particles, the attention has been directed to nanosystems and on their relevance to the bioavailability of poorly soluble drugs. A second advantage of such drug systems is that solubility increases on decreasing particle size, according to the Freundlich–Ostwald equation. The impact of polymorphism, pseudopolymorphism and amorphous form on drug dissolution and bioavailability is also described. Since dissolution and absorption are closely related, the effect of particle size and polymorphism on drug absorption is described. Moreover, regulatory implications of particle size and polymorphism are reviewed.