Otto Caputo

Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique.

A preparation method for nanoparticles based on the emulsification of a butyl lactate or benzyl alcohol solution of a solid lipid in an aqueous solution of different emulsifiers, followed by dilution of the emulsion with water, was used to prepare glyceryl monostearate nanodispersions with narrow size distribution. To increase the lipid load the process was conducted at 47+/-2 degrees C and in order to reach submicron size a high-shear homogenizer was used. Particle size of the solid lipid nanoparticles (SLN) was affected by using different emulsifiers and different lipid loads. By using lecithin and taurodeoxycholic acid sodium salt, on increasing the GMS percentage from 2.5 to 10% an increase of the mean diameter from 205 to 695 nm and from 320 to 368nm was observed for the SLN prepared using benzyl alcohol and butyl lactate, respectively. Transmission electron micrographs of SLN reveal nanospheres with a smooth surface.

Sterilization and freeze-drying of drug-free and drug-loaded solid lipid nanoparticles

Solid lipid nanoparticles (SLN) have been prepared from three oil-in-water microemulsions, whose internal phase was constituted of different lipid matrices. The dispersion media were two aqueous solution of trehalose and Pluronic F68 at 2% besides distilled water. SLN were sterilized by autoclaving, were stable during sterilization and maintained a spherical shape and narrow size distribution as confirmed by TEM analysis. SLN dispersions in water did not present nanoparticles larger than 1 μm after storage at 4°C for 1 year; they were freeze-dried after sterilization to obtain dry products. Diazepam was used as model drug to incorporate into SLN, where it was shown by calorimetric analysis to be in amorphous form.

Preparation and characterization of solid lipid nanospheres containing paclitaxel

The study describes the development of stealth and non-stealth solid lipid nanospheres (SLNs) as colloidal carriers for paclitaxel, a drug with very low solubility. SLNs are constituted mainly of bioacceptable and biodegradable lipids, such as tripalmitin and phosphatidylcholine, and can incorporate amounts of paclitaxel up to 2.8%. Stealth and non-stealth loaded SLNs are in the nanometer size range and can be sterilized and freeze-dried. Thermal analysis (differential scanning calorimetry) showed that paclitaxel is not able to crystallize in the SLNs. Release of paclitaxel from SLNs is very low. Non-stealth and stealth SLNs are stable over time without precipitation of paclitaxel and can be proposed for its parenteral administration.

Solid Lipid Nanoparticles in Lymph and Plasma After Duodenal Administration to Rats

AbstractPurpose. To evaluate the uptake and transport of solid lipid nanoparticles (SLN), which have been proposed as alternative drug carriers, into the lymph and blood after duodenal administration in rats. Methods. Single doses of two different concentrations of aqueous dispersions of unlabelled and labelled SLN (average diameter 80 nm) were administered intraduodenally to rats. At different times, samples of lymph were withdrawn by cannulating the thoracic duct and blood was sampled from the jugular vein. Monitoring continued for 45 and 180 minutes, for unlabelled and labelled SLN respectively. The biological samples were analysed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and gamma-counting. Results. TEM analysis evidenced SLN in lymph and blood after duodenal administration to rats; the size of SLN in lymph did not change markedly compared to that before administration. The labelled SLN confirmed the presence of SLN in lymph and blood. Conclusions. The uptake and transport of SLN in the lymph, and to a lesser extent in the blood, were evidenced. The in vivo physical stability of SLN may have important implications in designing drug-carrying SLN.

Solid lipid nanoparticles as carriers of hydrocortisone and progesterone complexes with β-cyclodextrins

Inclusion complexes of hydrocortisone and progesterone were formed with β-cyclodextrin or 2-hydroxypropyl-β-cyclodextrin. The formation of the complexes was confirmed by differential scanning calorimetry (DSC). The inclusion complexes were incorporated in two types of solid lipid nanoparticles (SLN). In the presence of the complexes the sizes of SLN remained below 100 nm. DSC analysis showed that hydrocortisone and progesterone are dispersed in SLN in an amorphous state. Using the β-cyclodextrin complexes the incorporation of the more hydrophilic drug, hydrocortisone, was higher than that of progesterone. Release of hydrocortisone and progesterone from SLN was lower when they were incorporated as inclusion complexes than as free molecules.

Solid lipospheres of doxorubicin and idarubicin

Abstract Solid lipospheres, constituted mainly of stearic acid and egg lecithin, containing amounts of doxorubicin and idarubicin up to 7 and 8.4%, respectively, were prepared. The high incorporation of drug is due to an increase in their lipophilicity as a result of the formation of ion-pairs with monoalkyl phosphate esters.

Phagocytic uptake of fluorescent stealth and non-stealth solid lipid nanoparticles

Abstract Fluorescent non-stealth and stealth solid lipid nanoparticles (SLN) were prepared using rhodamine B base as fluorescent marker. The steric stabilization of the nanoparticles was obtained using two lipid derivatives of monomethylpoly(ethylene) glycol 2000 (PEG 2000) as stealth agents: dipalmitoylphosphatidylethanolamine-PEG 2000 and stearic acid-PEG 2000. Stealth and non-stealth SLN were in the nanometer size range. Phagocytosis was evaluated by incubating SLN with murine macrophages and determining the extent of phagocytic uptake spectrofluorimetrically; stealth SLN inhibited phagocytosis to a greater extent than did non-stealth SLN.

Scale-up of the preparation process of solid lipid nanospheres. Part I.

An apparatus was designed to prepare solid lipid nanospheres (SLN), potential colloidal therapeutic system obtained by dispersing a warm oil-in-water (o/w) microemulsion in cold water. The apparatus, consisting mainly of a thermostated aluminium chamber and a pneumatic piston, permitted to disperse through a needle up to 100 ml of warm microemulsion and to vary the temperature, the dispersing rate and the drop size of the warm o/w microemulsion. Experimental design was applied to study the effect of four experimental factors, such as chamber temperature, piston pressure, needle gauge and volume of dispersing water, on average diameter and polydispersity index of SLN and on dispersing time of microemulsion (the time required for the microemulsion to drip completely from the apparatus). The results showed that temperature and pressure play the most important roles depending on the needle gauge used. In particular, the smallest SLN were obtained using high temperature and pressure values and a small needle gauge.

Effects of ultrasound-assisted compaction on Ketoprofen/Eudragit® S100 Mixtures

Ketoprofen alone and in binary mixtures with Eudragit S100 was compacted by an ultrasound-assisted (US) tableting machine at an energy ranging from 50 to 400 J. The final material was analysed by TLC and HPLC: no decomposition product of the active agent was found. IR spectra and HSM revealed the absence of any interaction between the two components. Thermal analysis (DSC) evidenced that ketoprofen inside the mixtures was transformed into an amorphous state, documented by the decreasing of the DeltaHfus as the Eudragit/ketoprofen ratio increases and as US energy increases. While pure ketoprofen recovers its crystalline state quickly after the US treatment, the presence of Eudragit was found to slow down or possibly to prevent the regeneration of the crystallinity.

Evaluation of theophylline tablets compacted by means of a novel ultrasound-assisted apparatus

Abstract A model formulation containing theophylline and Eudragit® RL was compacted, at energies ranging between 15 and 150 J, by means of a laboratory-scale, novel tabletting machine in which compaction was effected by ultrasound, rather than by mechanical energy. Comparison of the technological and physico-chemical characteristics of the resulting tablets with those of tablets obtained with a conventional tabletting machine evidenced significant differences, suggesting sintering as the main mechanism operating in ultrasound-assisted compaction. The ultrasound-compacted tablets released the drug at lower rates with respect to conventional tablets. The novel technique migh prove useful for the development of sustained-release oral dosage forms containing theophylline or other suitable drugs.