Investigations of the effect of the lipid matrix on drug entrapment, in vitro release, and physical stability of olanzapine-loaded solid lipid nanoparticles

The purpose of this research was to study the effect of the lipid matrix on the entrapment of olanzapine (OL). OL-loaded solid lipid nanoparticles (SLNs) were prepared using lipids like glyceryl monostearate (GMS), Precirol ATO 5 (PRE), glyceryl tristearate (GTS), and Witepsol E85 (WE 85)—and poloxamer 407 and hydrogenated soya phosphatidylcholine as stabilizers—using a hot melt emulsification high-pressure homogenization technique, and then characterized by particle size analysis, zeta potential, differential scanning calorimetry (DSC), and powder X-ray diffraction (pXRD). Homogenization at 10 000 psi for 3 cycles resulted in the formation of SLNs with a mean particle size of ∼190 nm for the 4 lipids investigated. The highest partition coefficient for OL between the melted lipid and pH 7.4 phosphate buffer (pH 7.4 PB) was obtained with GTS. The entrapment efficiency was in the following order: GTS SLNs>PRE SLNs>WE 85 SLNs>GMS SLNs. DSC and pXRD showed that much of the incorporated fraction of OL existed in the amorphous state after incorporation into SLNs. A sharp increase in the flocculation of the SLN dispersions was observed upon addition of 0.6 M aqueous sodium sulfate solution. Nanoparticle surface hydrophobicity was in the following order: GTS SLNs>PRE SLNs>WE 85 SLNs>GMS SLNs. A significant increase in size and zeta potential was observed for GTS SLN and WE 85 SLN dispersions stored at 40°C. Release of OL from the SLNs was sustained up to 48 hours in pH 7.4 PB and obeyed Higuchi’s release kinetics

Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration

The purpose of this research was to investigate the effects of processing conditions on the characteristics of solid lipid microparticles (SLM) with a potential application as carriers for pulmonary administration. Compritol (5.0% wt/wt) SLM dispersions were prepared by rotor-stator homogenization, at different surfactant concentrations and emulsification times. The SLM were characterized, in terms of morphology and size, after lyophilization and sterilization by autoclaving process. In vivo assessment was carried out in rats by intratracheal instillation of either placebo or SLM dispersion, and by bronchoalveolar lavage for cytological analysis. Mean particle size of 4 to 5 μm was achieved using 0.3% and 0.4% (wt/wt) of emulsifier (Poloxamer 188) and emulsification times of 2 and 5 minutes. The particles showed spherical shape and smooth surface. The morphology of microparticles, the size, and the size distribution were not substantially modified after lyophilization and sterilization. Total cell counts showed no significant differences between placebo and SLM 0.5% or 2.5% groups. Regarding cytology, percentage of polymorphonuclear neutrophils and macrophages did not significantly differ between groups. These results suggest that a single intratracheal administration of the SLMs does not induce a significant inflammatory airway response in rats and that the SLMs might be a potential carrier for encapsulated drug via the pulmonary route

Recent Advances in Lipid Nanoparticle Formulations with Solid Matrix for Oral Drug Delivery

Lipid nanoparticles based on solid matrix have emerged as potential drug carriers to improve gastrointestinal (GI) absorption and oral bioavailability of several drugs, especially lipophilic compounds. These formulations may also be used for sustained drug release. Solid lipid nanoparticle (SLN) and the newer generation lipid nanoparticle, nanostructured lipid carrier (NLC), have been studied for their capability as oral drug carriers. Biodegradable, biocompatible, and physiological lipids are generally used to prepare these nanoparticles. Hence, toxicity problems related with the polymeric nanoparticles can be minimized. Furthermore, stability of the formulations might increase than other liquid nano-carriers due to the solid matrix of these lipid nanoparticles. These nanoparticles can be produced by different formulation techniques. Scaling up of the production process from lab scale to industrial scale can be easily achieved. Reasonably high drug encapsulation efficiency of the nanoparticles was documented. Oral absorption and bioavailability of several drugs were improved after oral administration of the drug-loaded SLNs or NLCs. In this review, pros and cons, different formulation and characterization techniques, drug incorporation models, GI absorption and oral bioavailability enhancement mechanisms, stability and storage condition of the formulations, and recent advances in oral delivery of the lipid nanoparticles based on solid matrix will be discussed