A new cyclodextrin-grafted viscose loaded with aescin formulations for a cosmeto-textile approach to chronic venous insufficiency.

Cosmeto-textile applications can be used in the treatment of chronic venous insufficiency in legs by means of elastic bandages loaded with natural products which possess flebotonic properties. We have developed an efficient synthetic procedure for the preparation of ß-cyclodextrin (ß-CD)-grafted viscose by means of a 2-step ultrasound-assisted reaction. The highly grafted fabric bearing bis-urethane bridged ß-CD has been characterized by ATR-FTIR and CP-MAS spectra and by an empiric colorimetric method which used phenolphthalein as the CD guest. We have also developed a suitable cosmetic preparation containing natural substances and extracts (aescin, menthol, Centella asiatica and Ginkgo biloba) to recharge the CD-grafted textile. The efficacy of the new cosmeto-textile has been corroborated by in vitro studies of diffusion through membranes, cutaneous permeation and accumulation in porcine skin. Aescin was taken as a reference compound and its concentration in the different compartments was monitored by HPLC analysis. This cost effective cosmeto-textile shows excellent application compliance and is easily recharged and so has the strong base characteristics needed for possible industrial production.

Solid lipid micro-particles carrying insulin formed by solvent-in-water emulsion-diffusion technique.

The study aimed to produce solid lipid insulin-loaded micro-particles by the solvent-in-water emulsion-diffusion technique, using isobutyric acid as solvent phase, glyceryl monostearate or cetyl palmitate as lipid, soya lecithin and taurodeoxycholate as emulsifiers. Isobutyric acid, a partially water-miscible solvent with low toxicity, was used due to its high insulin-solubilization capacity. Solid lipid micro-particles of spherical shape were prepared by simple dilution of the emulsion with water. To increase the lipid load the process was conducted at 50 degrees C, and in order to reach sub-micron size, a high-shear homogeniser was used. Insulin encapsulation efficiency was about 80%. Analysis of microsphere content after processing showed that insulin did not undergo any chemical modification within the micro-particles. The in vitro release of insulin from the micro-particles was very low, and an initial burst effect of 20% of the dose was observed. After treatment of the solid lipid micro-particles with pepsin solution, an insulin loss of about 24% of the total englobed insulin was observed. The solid lipid micro-particles appear to have interesting possibilities as delivery systems for oral administration of insulin.

Hemp-seed and olive oils: their stability against oxidation and use in O/W emulsions.

Hemp-seed oil has several positive effects on the skin: thanks to its unsaturated fatty acid (PUFA) content it alleviates skin problems such as dryness and those related to the aging process. We present a comparative study of hemp-seed and olive oils, determining some physicochemical indices and evaluating their stability against oxidation. The peroxide value of hemp-seed oil was below 20, the threshold limit for edible oils. Hemp-seed oil was less stable against peroxidation than olive oil, but MDA and MONO assays showed its stability to be above expectations. The chlorophyll contained in extra virgin olive oil had a higher photostability than that contained in hemp-seed oil, possibly due to the larger amount of antioxidant in the olive oil. A certain amount of Vitamin E was found in hemp-seed oil. Since quality analyses indicated that hemp-seed oil is relatively stable, emulsions were prepared with the two oils, and their stability and rheological characteristics were tested. Some of the resulting gel-emulsions were suitable for spraying on the skin.

Kinetics of dopamine oxidation by dialkylaminoalkylphenothiazine cation radicals.

The kinetics of dopamine oxidatinon dialkylaminoalkylphenothiazine cation radicals (with two- or three-carbon side chains) were investigated. The two-carbon side-chain derivatives have reaction rates higher than the three-carbon ones. For chlorpromazine and promazine, extrapolation of pH 1-6 data shows that reaction rates become very fast at physiological pH.

Kinetics and mechanism of oxidation of promazine and promethazine by ferric perchlorate.

The equilibrium constants, kinetics, and mechanism of promazine and promethazine oxidation by ferric perchlorate were investigated at different temperatures and acidities using a stopped-flow spectrophotometric technique. The overall reaction can be represented as follows: (formula: see text) where P+ represents the radical cation corresponding to the phenothiazine derivative. The equilibrium quotients were evaluated at 1.00 M HClO4, 25.0 degrees, and ionic strength 1.0 M. The kinetics of reaction follow the equation: -d[P] divided by dt = k1[Fe3+][P]-k-1[Fe2+][P+] The rate constants k1 and k-1 are independent of acidity and are related to the corresponding equilibrium quotients.

Behavior of ATP toward phenothiazine drugs.

The tricyclic amines promazine, promethazine, chlorpromazine, triflupromazine, and trifluperazine form solid ion pairs with ATP in a 1:2 molar ratio. There is a good correlation between the measured Ksp and the apparent diffusion constants of the ion pairs with the critical micelle concentration (CMC) of the corresponding phenothiazines. Solid ion pairs are solubilized by phenothiazine micelles; the binding constants of ATP to drug micelles are calculated from solubility data at 25 degrees C and can be related to the CMC of the phenothiazines.

Effect of carboxylic acids on permeation of chlorpromazine through dimethyl polysiloxane membrane.

The effect of carboxylic acids on the permeation of chlorpromazine was investigated through a dimethyl polysiloxane nonpolar membrane. The permeability of the diffusate, at pH 5.8, increases considerably in the presence of carboxylic acids or phosphate, probably due to an ion-pair formation between the relative anions and chlorpromazine.

Vitamin A and vitamin A palmitate stability over time and under UVA and UVB radiation.

Vitamin A and vitamin A palmitate photostability were tested in different media. Ethanol and octyl octanoate solutions of these two vitamins, as such and with the addition of sunscreens (3,4 methylbenzilidencanfora, butyl methoxy dibenzoylmethane and octyl methoxycinnamate) or beta-carotene and butylated hydroxy toluene, were analysed spectrophotometrically after UVB or UVA irradiation. An O/W fluid emulsion with 0.5% w/w of retinyl palmitate, with and without butylated hydroxy toluene, was prepared. The oil containing the vitamin was extracted with HCl and aluminium sulfate and analysed spectrophotometrically after UVB or UVA irradiation. The fluid emulsion containing retinyl palmitate with and without butylated hydroxy toluene was stored at different temperatures and analysed every week spectrophotometrically for a month. Of the sunscreens tested butyl methoxy dibenzoylmethane showed the strongest protective action towards vitamin A and vitamin A palmitate, whereas beta-carotene did not protect either vitamin. Butylated hydroxy toluene inhibited the photodegradation of both vitamins dissolved in octyl octanoate, suggesting that oxygen may be involved in their degradation. O/W emulsion promoted slightly the degradation of vitamin A ester. Butylated hydroxy toluene protected retinyl palmitate from degradation induced by light and heat.

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.

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.

Timolol in lipospheres.

Lipospheres carrying timolol (1) were obtained from microemulsions. They had lecithin, palmitic and decanoic acids as the main constituents. The sizes were between 300 and 400 nm and the amount of 1 incorporated varied from 2.7 to 4.8% according to the microemulsion used. Compound 1 was present in the lipospheres mainly as ion pairs in order to increase its lipophilicity. The difference found in the incorporation was principally due to the different lipophilicity of the ion pairs of 1.

Binding of Phenothiazines to bovine hemoglobin.

Phenothiazines with bovine hemoglobin give solid complexes in phosphate buffer; this is due to the presence of ion-pairs between phenothiazines and phosphates. Using diluted solutions the number of sites available on each protein molecule and the intrinsic binding constants are determinated; the number of sites, in solutions and in solid complexes, is about the same for each drug, but different for the various phenothiazines.

Behaviour of hematoporphyrin and protoporphyrin with antidepressant drugs.

Complexation between oppositely charged antidepressant drugs and porphyrin derivatives was investigated by NMR spectroscopy. The solid complexes obtained are soluble in antidepressant aggregates and a good fit was found between the values of CMC of the drugs and the values of the binding constants of porphyrins with antidepressant micelles.

Inhibition of lipoperoxidation of linoleic acid by five antioxidants of different lipophilicity.

The efficacy of oxidation inhibition of five natural and synthetic antioxidants (BHT, BHA, nordihydroguaiaretic acid (NDGA), quercetin and rutin) was studied in O/W emulsions. Linoleic acid was used as a reference molecule; the reaction was initiated by an azo-compound. The kAH characterizing the reaction of the antioxidant with the peroxyl radical decreases in the following order: kAH(BHA) > kAH(BHT) > kAH(NDGA) > kAH(quercetin) > kAH(rutin).

Vitamin A palmitate photostability and stability over time.

Vitamin A palmitate photostability in relation to UVA and UVB was tested in hydroxy ethyl cellulose hydrogels at pH 4.0, 5.6, 7.0, and 8.0, alone and with the addition of sunscreens (3,4-methylbenzilidencamphor or butyl methoxy dibenzoylmethane) or an antioxidant (butylated hydroxy toluene). The photostability of vitamin A palmitate was also tested in encapsulated systems (Tagravit A1 microcapsules, Lipotec liposomes, phosphatidylcholine liposomes, and Lipotec nanocapsules) dispersed in gels at pH 5.6 and 7.0. The stability of retinyl palmitate over time in hydroxy ethyl cellulose hydrogels at pH 5.6 and 7.0 (stored one month at 25 degrees C or 40 degrees C), alone or with butylated hydroxy toluene, was also tested. The stability of retinyl palmitate over time in encapsulated systems, dispersed in gels at pH 5.6 and 7.0, was also studied. O/W emulsions were also prepared to compare the stability of vitamin A palmitate introduced in a lipophilic/hydrophilic medium (O/W emulsions) and a hydrophilic medium (hydrogels). HPLC analysis showed that encapsulated systems such as Lipotec nanocapsules, Tagravit A1 microcapsules, phosphatidylcholine liposomes, and Lipotec liposomes protect the vitamin A ester over time from hydrolysis and from oxidation to retinaldeide and retinoic acid, and that Lipotec nanocapsules and phosphatidylcholine liposomes also improve the vitamin's photostability. A change in pH (from 5.6 to 7.0) of the gels did not influence the vitamin ester's stability. pH levels of 4.0 and 8.0 determined a decrease in the stability of retinyl palmitate in the gels. A high concentration of sunscreens improved the photostability of retinyl palmitate in the gels at pH 5.6 and 7.0. Butylated hydroxy toluene protected retinyl palmitate from degradation induced by light at all the pH levels studied and by heat at pH 5.6 and 7.0, as can be seen from the study of the photostability of vitamin A palmitate under UVB and UVA and of stability over time. Rheological studies showed a slight decrease in the viscosity of the gels after UVB-UVA irradiation and a higher decrease in the viscosity of the gels and the emulsions after storage at 25 degrees C and 40 degrees C. This decrease can be attributed to a partial degradation of hydroxy ethyl cellulose and of emulsifier, as can be seen from the decrease in shear stress versus shear rate values under these conditions of storage, denoting a depolymerization of the rheological modifier.

Photostability of naturally occurring whitening agents in cosmetic microemulsions.

An o/w microemulsion formulated using lecithin and an alkyl glucoside as mild, non-irritant surfactants was proposed as a cosmetic vehicle for arbutin and kojic acid, naturally occurring whitening agents. After assessing the physicochemical stability of the microemulsion in the presence and absence of whitening agents, several perfumed compositions, developed using fragrant molecules of natural or synthetic origin, were introduced, and the olfactory impact of the perfumed microemulsion was evaluated. The photostability to UVB irradiation of both whitening agents was determined in aqueous solutions and in microemulsions, and also in the presence of the perfumed compositions. The stability of arbutin and kojic acid was higher in microemulsions than in aqueous solutions, and only in some cases did the presence of odorous molecules appear to influence it: linalool exerted some protective effect towards kojic acid photodegradation.

[Formation of an azoderivative of phenothiazine]. / Sulla formazione di un azoderivato della fenotiazina

The reaction of phenothiazine-5-oxide in 2 N HCl with 2,4-dinitrophenylhydrazine gives rise to 3-azo-(2',4'-dinitrophenyl)phenothiazine and phenothiazine. The stoichiometric ratio is two molecules of phenothiazine-5-oxide to one molecule of 2,4-dinitrophenylhydrazine.

In vitro release of propranolol from oil/water microemuisions.

Synopsis Oil/water (o/w) microemulsions containing propranolol were studied. Isopropylmyristate was used as the oil, Tween 60 as a surfactant, butanol as a co-surfactant and a buffer of pH 6.5 for the continuous phase. The lipophilicity of propranolol was enhanced by formation of lipophilic ion-pairs to obtain a disperse phase that could act as a reservoir; octanoic acid was used as counter-ion. The diffusion rates of propranolol from microemulsions through a hydrophilic membrane decreased as the concentration of octanoic acid increased. The apparent permeability constant, determined at the beginning of the experiment, was 2.9 x 10(-9) cm s(-1) for propranolol alone and diminished until 3.5 x 10(-10) cm s(-1) in the presence of octanoic acid, at a concentration of 16.4 times that of propranolol.