Solid Lipid Nanoparticles: A Strategy to Improve Oral Delivery of the Biopharmaceutics classification system (BCS) Class II Drugs

Abstract

In drug discovery, approximately 70% of new drug candidates have shown poor aqueous solubility
in recent years. Currently, approximately 40% of the marketed immediate release (IR) oral drugs are
categorized as practically insoluble (<100 g/mL). The aqueous solubility of a drug is a critical determinant
of its dissolution rate. The Biopharmaceutics Classification System (BCS) is a useful tool for decisionmaking
in formulation development from a biopharmaceutical point of view. BCS Class II drugs are
identified as low solubility and high permeability. In general, the bioavailability of a BCS Class II drug is
rate limited by its dissolution so that even a small increase in dissolution rate sometimes results in a large
increase in bioavailability. Therefore, an enhancement of the dissolution rate of the drug is thought to be
a key factor for improving the bioavailability of BCS Class II drugs. Solid lipid nanoparticles (SLNs)
were developed in the mid-1980s as an alternative system to the existing traditional carriers (emulsions,
liposomes, microparticles, and their polymeric counterparts) when Speiser prepared the first micro- and
nano-particles (named nano pellets) made up of solid lipids for oral administration. SLNs are colloidal
carriers made up of lipids that remain solid at room temperature and body temperature and also offer unique
properties such as small size (50–500 nm), large surface area, high drug loading, and the interaction of
phases at the interfaces and are attractive for their potential to improve performance of pharmaceuticals,
nutraceuticals, and other materials. Moreover, SLN are less toxic than other nanoparticulate systems
due to their biodegradable and biocompatible nature. SLN is capable of encapsulating hydrophobic
and hydrophilic drugs, and they also provide protection against chemical, photochemical, or oxidative
degradation of drugs, as well as the possibility of a sustained release of the incorporated drugs.