Marina Gallarate

On the stability of ascorbic acid in emulsified systems for topical and cosmetic use

Several O/W microemulsions, O/W and W/O emulsions and a W/O/W multiple emulsion were prepared using non-ionic, non-ethoxylated, skin compatible emulsifiers. Ascorbic acid (vitamin C) was added to the emulsified systems and its stability against oxidation was studied at 45.0 degrees C in aerobic conditions and compared with that in aqueous solutions at different pH values. All emulsified systems provided protection to ascorbic acid, as its degradation rate, which increased with increasing pH, was slower in emulsified systems than in aqueous solutions. The highest protection of ascorbic acid was when it was dissolved in the inner aqueous phase of the W/O/W multiple emulsion, both at 45 and at 20 degrees C for long storage. A pseudo first-order mechanism was hypothesised for ascorbic acid degradation in the experimental conditions for as long as abundant dissolved oxygen was present.

Elastic liposomes for skin delivery of dipotassium glycyrrhizinate.

The aim of this study was to evaluate the possibility of using liposomes for skin delivery of dipotassium glycyrrhizinate (KG), an anti-inflammatory agent employed in treating acute and chronic dermatitis, and of formulating such liposomes in an oil-in-water emulsion (O/W). KG had emulsifying properties and the possibility of producing elastic liposomes was verified. Liposomes containing soya lecithin (PC) or hydrogenated soya lecithin (HPC) mixed with KG in w/w ratios of 2:1, 4:1 or 8:1 were prepared by the solvent evaporation method and then passed through a high pressure homogeniser. Liposome size and entrapment efficiency were determined and the interaction between KG and HPC was investigated using differential scanning calorimetry (DSC). Transepidermal permeation through intact pig skin and skin deposition of KG from liposomes and O/W emulsion containing liposomes were assessed and compared with values for aqueous control solutions. No marked differences were observed between PC and HPC liposomes. Liposome sizes ranged from 90 to 120 nm. Entrapment efficiency depended on the lipid:KG ratio; the maximum efficiency was obtained at 4:1 w/w. KG interacted with liposomes disrupting and fluidising the lipid bilayer, forming elastic liposomes able to penetrate through membrane pores of diameter much smaller than their own diameter. The liposome structure was maintained when dispersed in an O/W emulsion. The skin fluxes were less than the HPLC detection limit for all systems, while skin deposition increased 4.5-fold compared with aqueous solutions when KG was formulated in liposomes.

Emulsions containing partially water-miscible solvents for the preparation of drug nanosuspensions

The aim of this study was to investigate the feasibility of partially water-miscible solvents, such as benzyl alcohol, butyl lactate and triacetin, to prepare drug nanosuspensions by a solvent quenching technique. Mitotane, which possesses very poor water solubility and low bioavailability, was used as model drug. Preparation was by emulsifying an organic solution of the drug in an aqueous solution of a stabilising agent followed by rapid displacement of the solvent from the internal into the external phase, provoking solid particle formation. To verify the influence of emulsion droplet size on the drug particle size, 0.1 or 0.2% of different emulsifiers (Tween 80, caprylyl-capryl glucoside or lecithin) and different homogenisation conditions (Ultra Turrax or a high pressure homogenizer at 200 or 1000 bar for three cycles) were used. In general, emulsion droplet size decreased with high pressure homogenization and on increasing the number of cycles. The size of drug particles, obtained after adding water at a constant rate, was dependent on the droplet size in the emulsion. Drug particles of approximately 80 nm were obtained using butyl lactate, supporting the hypothesis that drug particle formation by the emulsification diffusion process involves generating regions of local supersaturation. Because of the increase in available surface area, the dissolution rate of diaultrafiltrated suspensions increased greatly compared to commercial product.

Lipid nanoparticles: state of the art, new preparation methods and challenges in drug delivery

Introduction: Nanoparticles are rapidly developing as drug carriers because of their size-dependent properties. Lipid nanoparticles (LNPs) are widely employed in drug delivery because of the biocompatibility of the lipid matrix. Areas covered: Many different types of LNPs have been engineered in the last 20 years, the most important being solid lipid nanoparticles (SLNs), nanostrucured lipid carriers (NLCs), lipid–drug conjugates (LDCs) and lipid nanocapsules (LNCs). This review gives an overview of LNPs, including their physico-chemical properties and pharmacological uses. Moreover, it highlights the most important innovations in the preparation techniques of LNPs, aimed to encapsulate different molecules within the lipid matrix. Finally, it gives a short perspective on the challenges of drug delivery, which are a potential field of application for LNPs: cancer therapy, overcoming the blood–brain barrier and gene and protein delivery. Expert opinion: LNPs are a safe and versatile vehicles for drug and active delivery, suitable for different administration routes. New technologies have been developed for LNP preparation and studies are currently underway in order to obtain the encapsulation of different drugs and to deliver the active molecule to the site of action.

PREPARATION OF GRISEOFULVIN NANOPARTICLES FROM WATER-DILUTABLE MICROEMULSIONS

Nanoparticles of griseofulvin, a model drug with poor solubility and low bioavailability, were prepared from water dilutable microemulsions by the solvent diffusion technique. Solvent-in-water microemulsion formulations containing water, butyl lactate, lecithin, taurodeoxycholate sodium salt (TDC) or dipotassium glycyrrhizinate (KG), 1,2-propanediol or ethanol were used. The formation of macroscopically homogeneous, stable, fluid, optically transparent, isotropic solutions (microemulsions) was investigated by constructing pseudo-ternary phase diagrams. In the presence of TDC or KG, microemulsion systems that remained transparent on water dilution could be obtained. The displacement of butyl lactate, with an excess of water, from the internal phase of the microemulsions containing the drug into the external phase, lead to successful fabrication of drug nanosuspensions. Nanoparticle size was dependent on microemulsion composition: using KG, griseofulvin nanoparticles below 100 nm with low polydispersity and an increased dissolution rate were obtained.

In vitro permeation of azelaic acid from viscosized microemulsions

Abstract The transport of azelaic acid, a bioactive molecule used in treating acne and many skin disorders, from a viscosized microemulsion and from a gel through full thickness abdominal skin was examined. A lag time was evident in both systems. The percentage of azelaic acid transported from the microemulsion was several times higher than that from the gel. The effect of dimethyl sulfoxide, chosen as a model enhancer, on transport was also investigated. After 8 h from the viscosized microemulsions, 43 and 64% of the initial amount passed through hairless skin in the presence of 1 and 2% of dimethyl sulfoxide, respectively.

Preparation of solid lipid nanoparticles from W/O/W emulsions: Preliminary studies on insulin encapsulation

Abstract A method to produce solid lipid nanoparticles (SLN) from W/O/W multiple emulsions was developed applying the solvent-in-water emulsion-diffusion technique. Insulin was chosen as hydrophilic peptide drug to be dissolved in the acidic inner aqueous phase of multiple emulsions and to be consequently carried in SLN. Several partially water-miscible solvents with low toxicity were screened in order to optimize emulsions and SLN composition, after assessing that insulin did not undergo any chemical modification in the presence of the different solvents and under the production process conditions. SLN of spherical shape and with mean diameters in the 600–1200 nm range were obtained by simple water dilution of the W/O/W emulsion. Best results, in terms of SLN mean diameter and encapsulation efficiencies, were obtained using glyceryl monostearate as lipid matrix, butyl lactate as a solvent, and soy lecithin and Pluronic®F68 as surfactants. Encapsulation efficiencies up to 40% of the loaded amount were obtained, owing to the actual multiplicity of the system; the use of multiple emulsion-derived SLN can be considered a useful strategy to encapsulate a hydrophilic drug in a lipid matrix.

Solid lipid nanoparticles as vehicles of drugs to the brain: current state of the art.

Central nervous system disorders are already prevalent and steadily increasing among populations worldwide. However, most of the pharmaceuticals present on world markets are ineffective in treating cerebral diseases, because they cannot effectively cross the blood brain barrier (BBB). Solid lipid nanoparticles (SLN) are nanospheres made from biocompatible solid lipids, with unique advantages among drug carriers: they can be used as vehicles to cross the BBB. This review examines the main aspects surrounding brain delivery with SLN, and illustrates the principal mechanisms used to enhance brain uptake of the delivered drug.

Investigation of the phase behaviour of systems containing lecithin and 2-acyl lysolecithin derivatives

A series of modified phospholipids (m-PC) possessing different acyl chains in position 2, from butanoyl to hexadecanoyl, were prepared by partial synthesis from soybean lysolecithin. They were used with soybean lecithin to construct phase diagrams containing ethanol as cosolvent, water and medium chain triglycerides (MCT) or isopropyl myristate (IPM) as oils. The weight ratios lecithin:m-PC and surfactants:ethanol were kept constant at 1:1. The results indicate that the m-PCs have a strong effect on the microemulsion (L) and liquid crystalline (LC) domains in the water-rich/oil-poor part of the phase diagrams, although all diagrams correspond to a single lecithin:m-PC ratio. On decreasing the acyl chain length, and thus increasing the hydrophilicity of the surfactant, there was a corresponding increase in the L area, which moved towards the aqueous corner of the phase diagrams. The LC phase was detected only in the presence of the hexadecanoyl derivative for the systems containing MCT, and it was not detected only in the presence of the butanoyl derivative for the systems containing IPM. The use of a second hydrophilic surfactant to adjust the packing properties of the lecithin-alcohol systems, and/or to increase the fluidity of the surfactant film, increased the region of existence of the isotropic systems. This may be of importance in the formulation of drug delivery systems, especially those which are diluted by biological fluids upon administration.

Solid lipid nanoparticles formed by solvent-in-water emulsion-diffusion technique: development and influence on insulin stability.

Insulin-loaded solid lipid nanoparticles (SLN), obtained by the solvent-in-water emulsion–diffusion technique, were produced using isovaleric acid (IVA) as organic phase, glyceryl mono-stearate (GMS) as lipid, soy lecithin and sodium taurodeoxycholate (TDC) as emulsifiers. IVA, a partially water-miscible solvent with low toxicity, was used to dissolve both insulin and lipids. SLN of spherical shape were obtained by simple water dilution of the O/W emulsion. Analysis of SLN content after processing showed interesting encapsulation efficiency with respect to therapeutic doses; moreover, insulin did not undergo any chemical modification within the nanoparticles and most of it remained stable after incubation of the SLN with trypsin solution. The biological activity of insulin, i.e. the ability to decrease glycemia in rats, was not negatively influenced by the SLN production process, as after subcutaneous administration of insulin extracted from SLN to animals, the blood glucose levels were quite similar to those obtained after administration of a conventional insulin suspension. Consequently, SLN seem to have interesting possibilities as delivery systems for oral administration of insulin.