Drug Nanocrystals: Theoretical Background of Solubility Increase and Dissolution Rate Enhancement

Abstract

The peculiar higher solubility of drug nanocrystals compared to macrocrystals appeals to the pharmaceutical field. Indeed, until now, about 70 % of the potential drug candidates are discarded due to low bioavailability related with poor solubility in water. Since a modern and efficient design strategy for nanocrystal-based delivery systems requires the knowledge of the theoretical relation between nanocrystal size and solubility, the aim of this paper is to build up a physically-oriented thermodynamic model relating to nanocrystal dimensions with their melting temperature, enthalpy, solubility and dissolution rate. In particular, the developed model will be applied to vinpocetine, a poorly soluble drug used in the treatment of various types of cerebrovascular circulatory disorders.

Mathematical Modeling of Drug Release from Natural Polysaccharides Based Matrices

“…This is typical of anhydrous solids hydrating upon contact with the aqueous swelling solvent as it happens in the case of anhydrous theophylline that hydrates upon dissolution in water [59]. A similar behavior takes place in nanocrystalline and amorphous drug (amorphous state may be considered as a crystal of vanishing dimensions) that, upon dissolution, tend to return to the more thermodynamically stable microcrystal condition [58,[60][61][62]. Notably, recrystallization implies a reduction of drug solubility, this being of paramount importance with regard to drug bioavailability [63].…”

“…Indeed, solvent makes possible a very crucial phenomenon: drug dissolution in the solvent. Strictly speaking, dissolution may be viewed as the sum of four consecutive steps [58]: 1) contact of the solid drug surface with the incoming solvent (wetting) 2) breakdown of solid molecular bonds (fusion) 3) transfer of solid molecules to the solid/liquid interface (solvation) and 4) movement of the solvated molecules from the interfacial region into the bulk solution (diffusion). When metastable solid structures are involved, dissolution process may be accompanied by recrystallization.…”

FSE–Ag complex NS: preparation and evaluation of antibacterial activity

“…This enhancement in solubility could be attributed to increased surface area due to decreased particle size and also amorphous nature of particles. It is well known that solubility increases with decrease in drug nanocrystal size [32].…”

Determination of Inherent Dissolution Performance of Drug Substances

“…For many years, drug dissolution has been described by diffusion models, such as Noyes-Whitney [7] and Hixson-Crowell [8]. Later approaches such as those developed by Higuchi [9] and Siepmann [10] as well as Göpferich, Langer [11] and Hasa [12] are based on Fick's law [13]. More recently, drug-solvent interactions have been shown to affect drug release in addition to diffusion [14][15][16].…”