The Role of Particle Size in Drug Release and Absorption

Abstract

AbstractSolid drug delivery systems are crucial formulations via the oral route. In such drug systems, particle size has a strong impact on drug dissolution and on drug absorption. Its role in dissolution rate is described starting from the Noyes–Whitney equation, the modified form by Nerst–Brunner and the cube root equation. According to these equations diffusion of solute through a boundary layer around the particles is the rate limiting step in both drug dissolution and absorption and, thus, depends upon the specific (external) surface area of the particles, the diffusion coefficient of the solute, the thickness of the boundary layer and the solute 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 is directed to nanosystems and on their relevance to the bioavailability of poorly soluble drugs. A second advantage of such drug systems is that the solubility increases with decreasing particle size, according to the Freundlich–Ostwald equation. Since dissolution and absorption are closely related, the impact of particle size on drug absorption is described. Moreover, regulatory implications of particle size are reviewed.KeywordsDissolution RateSolid DispersionSoluble DrugBiopharmaceutical Classification SystemDiffusion Boundary LayerThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.