Nanocrystals of Poorly Soluble Drugs: Drug Bioavailability and Physicochemical Stability

Abstract

Many approaches have been developed over time to overcome the bioavailability limitations of poorly soluble drugs. With the advances in nanotechnology in recent decades, science and industry have been approaching this issue through the formulation of drugs as nanocrystals, which consist of “pure drugs and a minimum of surface active agents required for stabilization”. They are defined as “carrier-free submicron colloidal drug delivery systems with a mean particle size in the nanometer range, typically between 10–800 nm”. The primary importance of these nanoparticles was the reduction of particle size to nanoscale dimensions, with an increase in the particle surface area in contact with the dissolution medium, and thus in bioavailability. This approach has been proven successful, as demonstrated by the number of such drug products on the market. Nonetheless, despite the definition that indicates nanocrystals as a “carrier-free” system, surface active agents are necessary to prevent colloidal particles aggregation and thus improve stability. In addition, in more recent years, nanocrystal properties and technologies have attracted the interest of researchers as a means to obtain colloidal particles with modified biological properties, and thus their interest is now also addressed to modify the drug delivery and targeting. The present work provides an overview of the achievements in improving the bioavailability of poorly soluble drugs according to their administration route, describes the methods developed to overcome physicochemical and stability-related problems, and in particular reviews different stabilizers and surface agents that are able to modify the drug delivery and targeting.

Pure Trans-Resveratrol Nanoparticles Prepared by a Supercritical Antisolvent Process Using Alcohol and Dichloromethane Mixtures: Effect of Particle Size on Dissolution and Bioavailability in Rats

“…In the 'top-down' and 'bottom-up' methods, water containing surface stabilizers was used as a dispersion medium or an antisolvent. To transform the phytochemicals into the solid form, nanosuspensions are dried by spray-drying and fluidized bed granulation after the addition of dispersants (usually sucrose and mannitol) to reduce the aggregation of nanoparticles during solidification and enhance nanoparticle redispersion in water [27,28]. These methods have some disadvantages, such as the use of massive additives.…”

Emerging role of nanosuspensions in drug delivery systems

“…This can decrease the dissolution velocity and bioavailability particularly poorly water soluble BCS II drugs. Formulation of low dose drugs with total nanoparticle content less than 1% relative to total tablet weight is effective in releasing it as fine nanosuspension to the solution [9].…”

The Polymorphism of Drugs: New Approaches to the Synthesis of Nanostructured Polymorphs

“…The methods used for improving the solubility, dissolution rate, and bioavailability of solid medicinal substances are being developed and improved. In the last two decades, in order to enhance the solubility and bioavailability of drugs, in addition to drugs in the form of salts [2], attention has been focused on the preparation of solid amorphous dispersions [3,4], dispersions containing nanocrystals [5,6], and the synthesis of co-crystals [7,8]. Additionally, when resolving the problem of improving the bioavailability, the polymorphism phenomenon, which is defined as the possibility for the original molecule to exist in two or more crystal states, plays an important role [9][10][11].…”