F. M. Riccieri

Modulation of caffeine skin delivery by carrier design: liposomes versus permeation enhancers

Abstract Delivery systems for caffeine have been designed for two different purposes: (1) enhancing drug permeation through the skin for systemic delivery and (2) accumulating drug reservoir in the skin for local delivery. Caffeine exhibited concentration-dependent growth inhibition of normal and psoriatic human fibroblasts, as well as 3T3 mouse fibroblasts. High flux of caffeine through the skin was obtained from an aqueous solution containing an enhancing mixture of 20% Transcutol and 10% oleic acid. The presence of the enhancers resulted in caffeine flux 40 times greater than in their absence. The high flux of caffeine through the skin in vitro which was obtained using the enhancing composition was shown to be parallel to increased serum concentrations of drug in rats in vivo. Application of caffeine in aqueous solution containing enhancing mixture resulted in high serum concentrations of 50–60 μ ml after 1 h, which remained high for at least 12 h following. The greatest caffeine accumulation in the skin was measured from small liposomal vesicles, 2260 solμg cm 2 , this being 3 times greater than from aqueous solution containing enhancers, the system which exhibited the second largest accumulation of drug in the skin. Using quantitative skin autoradiography, it was found that after 24 h, the greatest concentration of caffeine (280 μg g tissue) was localized in the epidermis and the lowest amount (50 μg g tissue) in the dermis. In addition, a relatively high concentration of caffeine was found in the appendages.

Preparation and properties of new unilamellar non-ionic/ionic surfactant vesicles

Abstract Non-ionic surfactant vesicles (NSVs) were prepared from polysorbate 20 and cholesterol by means of two different methods: by direct sonication of an aqueous dispersion of the various components (bulk) or by solubilization of the components, evaporation of the organic solvent to form a film inside the vessel used for the preparation and then by sonication (film). The influence of the preparation technique on the properties of the obtained structures was studied. Vesicles with bigger dimensions and higher entrapment efficiency were obtained when sonication was carried out after the film formation. Vesicle formation in the presence of ionic surfactants was investigated in order to evaluate the effect of charged components on vesicle dimensions, entrapment efficiency and stability. Dimethyldioctadecylammonium bromide (DDOA) and cetylpyridinium chloride (CPy) were used to introduce a positive charge in the vesicle structure, while dicetylphosphate (DCP) was used for a negative charge. Better resistance to osmotic stress and higher entrapment efficiency values were obtained with vesicles containing DCP and CPy.

A novel co-crosslinked polysaccharide: studies for a controlled delivery matrix

The formulation of a new controlled delivery system, based on a novel type of matrix obtained by the chemical reaction carried out in an aqueous medium on a mixed physical gel of gellan and scleroglucan, is described in this paper. The preparation yielded a new co-crosslinked polysaccharide (CCP) hydrogel, bearing carboxylic groups, that showed a sustained release behaviour that can be modulated by means of calcium ions. For the characterization of CCP, diffusion experiments through the swelled hydrogel were carried out in different environmental conditions and the release from tablets prepared with CCP and a model drug was evaluated. The addition of CaCl2 in the formulation of the dosage forms allowed a further marked reduction in delivery rate to be obtained; this effect is to be related to the free ionized carboxylic groups still present in the gellan moiety of CCP. The different behaviour of Ca+2 and Na+ ions is discussed.

Novel hydrogel system from scleroglucan: synthesis and characterization

New hydrogels obtained by a crosslinking reaction between the polycarboxylated derivative of scleroglucan (sclerox) and 1, 6-hexanedibromide have been prepared and characterized. Different ratios between the alkane dihalide and sclerox yielded products with appreciably different properties. Water uptake by the hydrogel with a low degree of crosslinking was remarkably affected by ionic strength. The diffusion of a model molecule (theophylline) through the swelled crosslinked polymers was studied and the theoretical analysis leading to the calculation of permeability coefficients in different environmental conditions is reported. Tablets prepared with one of the new hydrogels behaved as swellable monolithic systems suitable for sustained drug release.

Gellan for the formulation of sustained delivery beads

Gellan beads containing a model molecule, clay, and in most cases oil and a surfactant were prepared. The release from the obtained beads was studied in vitro with different techniques and the effects of the presence of varying amounts of oil in the formulation was investigated. The behaviour of gellan was compared with that of alginate in the same experimental conditions. The results indicate that gellan is suitable for the formulation of sustained release beads and that, for the tested preparations, the presence of oil results in a marked reduction in delivery rate. From release experiments, carried out with the various formulations and with different concentrations of the substances used as models, it can be suggested that the swelling of the matrix seems to be the most likely factor responsible for the overall rate of delivery.

Gellan in sustained release formulations: preparation of gel capsules and release studies

The ability of gellan to form gels in the presence of calcium ions enabled us to prepare capsules by gelation of this polysaccharide around a core containing starch, calcium chloride and a model drug. Release from the dried capsules was studied in vitro by means of the rotating basket technique (USP) in different environmental conditions (distilled water, pH = 2.0, pH = 6.8) and the effects of the presence of increasing amounts of drug in the formulation were also investigated. The behaviour of the gellan capsules was compared with that of beads prepared with the same polysaccharide but containing different additives. Results obtained indicate that gellan is suitable for the formulation of sustained release capsules and that solvent uptake by the dried capsules is most likely the main factor capable of affecting the rate of delivery from the tested preparations.

Ascorbic acid in aqueous solution : bathochromic shift in dilution and degradation

Spectrophotometric and conductivity determinations were performed for aqueous solutions of ascorbic acid in the concentration range of 5.7 × 10−5 to 10− M. The results show a significant bathochromic shift of up to 30 nm of λmax with a decrease in ascorbic acid concentration. The discrepancy between the absorbance values at λmax and λfix was found to reach up to three absorbance units. These results have important implications for ascorbic acid stability tests and other systems in which ascorbic acid degradation occurs. When absorbance is directly read for ascorbic acid solutions of various concentrations, λmax should be determined for each individual solution.