The influence on the oral bioavailability of solubilized and suspended drug in a lipid nanoparticle formulation: In vitro and in vivo evaluation.

The present study investigated the oral bioavailability of celecoxib when incorporated into solid lipid nanoparticles either dissolved or suspended. In vitro drug release in different media, in vivo performance, and in vitro-in vivo correlation were conducted. The results revealed that the compound was successfully encapsulated into the nanocarriers with good physicochemical properties for oral administration. The in vitro release profiles followed the Weibull model, with significant differences between the formulations containing the solubilized and the suspended compound. Furthermore, in vitro release data could be used to rank the observed in vivo bioavailability. The relative bioavailability of celecoxib from the solid lipid nanoparticles was 2.5- and 1.8-fold higher for the drug solubilized and suspended solid lipid nanoparticle formulation, respectively, when compared to the celecoxib reference. A significant difference was observed between the plasma concentration-time profiles and pharmacokinetic parameters for the three investigated formulations. Finally, this investigation displayed promising outcomes that both solubilized and suspended celecoxib in the lipid core of the solid lipid nanoparticles offers the potential to improve the compound's oral bioavailability and thereby reduce the dosing frequency.

Application of solid lipid nanoparticles as a long-term drug delivery platform for intramuscular and subcutaneous administration: In vitro and in vivo evaluation.

The purpose of this work was to evaluate solid lipid nanoparticles (SLNs) as a long acting injectable drug delivery platform for intramuscular and subcutaneous administration. SLNs were developed with a low (unsaturated) and high (supersaturated) drug concentration at equivalent lipid doses. The impact of the drug loading as well as the administration route for the SLNs using two model compounds with different physicochemical properties were explored for their in vitro and in vivo performance. Results revealed that drug concentration had an influence on the particle size and entrapment efficiency of the SLNs and, therefore, indirectly an influence on the Cmax/dose and AUC/dose after administration to rats. Furthermore, the in vitro drug release was compound specific, and linked to the affinity of the drug compounds towards the lipid matrix and release medium. The pharmacokinetic parameters resulted in an increased tmax, t1/2 and mean residence time (MRT) for all formulations after intramuscular and subcutaneous dosing, when compared to intravenous administration. Whereas, the subcutaneous injections performed better for those parameters than the intramuscular injections, because of the higher blood perfusion in the muscles compared with the subcutaneous tissues. In conclusion, SLNs extend drug release, need to be optimized for each drug, and are appropriate carriers for the delivery of drugs that require a short-term sustained release in a timely manner.