Sunscreen immobilization on ZnAl-hydrotalcite for new cosmetic formulations

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Microporous and Mesoporous Materials 107 (2008) 180–189 www.elsevier.com/locate/micromeso

Sunscreen immobilization on ZnAl-hydrotalcite for new cosmetic formulations Luana Perioli a, Morena Nocchetti b, Valeria Ambrogi a, Loredana Latterini b, Carlo Rossi a, Umberto Costantino b,* a

Dipartimento di Chimica e Tecnologia del Farmaco, Universita` degli Studi di Perugia, Via del Liceo 1, 06123 Perugia, Italy b CEMIN ‘‘Centro di Eccellenza Materiali Innovativi Nanostrutturati’’, Dipartimento di Chimica, Universita` di Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy Received 31 October 2006; received in revised form 5 February 2007; accepted 13 February 2007 Available online 20 February 2007

Abstract Intercalation compounds of ZnAl-hydrotalcite with the UV absorber 5-benzoyl-4-hydroxy-2-methoxy-benzenesulphonate acid (4BHF) have been prepared by ion exchange procedure and used to obtain sunscreen stabilization for new cosmetic formulations. Compounds having a sunscreen loading from 26% to 38% w/w have been obtained changing the pH of the equilibrating solution. In fact, taking advantage of the bi-protic nature of 4BHF, the mono-anions, the di-anions or a mixture of mono- and di-valent anions have been intercalated into the hydrotalcite. The compounds obtained have been firstly characterized by TG, XRPD, DSC, and SEM techniques, and then dispersed in a suitable waterproof silicon cream to obtain new sunscreen formulations. The in vitro 4BHF release from the formulation has been determined. Furthermore, the intercalation products and their formulations have been investigated by means UV–vis absorption spectroscopy in order to study the matrix influence on sunscreen sunlight protection effect and on their photostability. The 4BHF intercalation between ZnAl-hydrotalcite lamellae can be considered a good strategy to increase the sunscreen stability and to prepare solar cosmetic formulations always more efficacious and safe.  2007 Elsevier Inc. All rights reserved. Keywords: Hydrotalcites; Intercalation; Sunscreen; Cosmetic formulation; Photostability

1. Introduction Protection against UV radiation has become an increasingly important issue in human life [1] and many ‘‘solar products’’ containing UV filter species, known also as sunscreens, are used. Photochemical stability is the most important characteristic of an effective and safe UV filter, since the light-induced decomposition of the sunscreen not only reduces its photoprotective power, but can also promote phototoxic or photoallergic contact dermatitis and photocross reaction with other molecules as drugs [2–4]. Therefore, the development of new sunscreen formulations suitable to reduce the above-mentioned effects is a *

Corresponding author. Tel.: +39 075 5855565; fax: +39 075 5855566. E-mail address: [email protected] (U. Costantino).

1387-1811/$ - see front matter  2007 Elsevier Inc. All rights reserved. doi:10.1016/j.micromeso.2007.02.021

challenge for manufacturers of safe cosmetic products. Recently the use of hydrotalcite-like compounds (HTlc) as hosts of sunscreens showed to be a good approach to improve their performances [5–11]. The HTlc is a rare example of lamellar solids with positively charged lamellae and exchangeable anions into interlamellar region. They are represented by the general formula ½MðIIÞ1x MðIIIÞx ðOHÞ2 ½Az x=z  nH2O, where M(III) can be Al, Cr, Fe, and M(II) can be Mg, Zn, Ni, Co; x ranges from 0.2 to 0.4. The substitution, in the brucite sheet, of some M(II) by M(III) ions gives rise to positive charges balanced by anions (Az) accommodated in the interlayer region where water molecules are also located [12–17]. By means of the anion exchange or direct synthesis procedures [12,16] or taking advantage of the ‘‘dissolution–reconstruction’’ of HTlc [18] it is possible to prepare intercalation compounds

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with a large variety of anionic species both inorganic and organic. The HTlc become hosts of species with magnetic, photochemical [19,20], optical, pharmaceutical [21–23] properties and, at the same time, the guest species are protected from oxidation and UV radiation and their properties are modulated because of the guest–guest and host–guest interactions. The present work deals with the intercalation of 5-benzoyl-4-hydroxy-2-methoxy-benzenesulphonic acid (4BHF), INCI name benzophenone-4, as mono- (m-4BHF) and/or di-anion (d-4BHF) into ZnAl-HTlc and with the preparation of the waterproof silicon creams containing the intercalation products. The performance of these formulations has been compared with those of the same formulations containing free 4BHF. 2. Experimental

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Furthermore several samples containing the 4BHF intercalated as mono-anion (m-4BHF) and/or di-anion (d-4BHF) were prepared equilibrating, for three days at 60 C, HTlc-NO3 with an 0.1 mol/dm3 4BHF aqueous solution at pH ranging from 3.9 (1 g HTlc/58 ml) to 9.9 (1 g HTlc/29 ml). In each case the 4BHF/Al molar ratio was fixed to 2. The solids, separated from the solution by centrifugation, were washed three times with CO2-free deionized water and finally dried at different R.H.: over a saturated NaCl solution (R.H. 75%) and over P4O10 (R.H.  0%). 2.3. Characterization of materials 2.3.1. X-ray diffraction analyses X-ray powder diffraction patterns (XRDP) were performed with a PW 1710 Philips diffractometer (Lelyweg, Netherland), using the Ni-filtered Cu Ka radiation.

2.1. Materials 4BHF was kindly provided by Prodotti Gianni, Milano (Italy), polygliceryl-4-isostearate cetyl dimethicone copolyol hexyl laurate (Abil WE 09) and polygliceryl-3-isostearate (Isolan GI 34) and cetyl dimethicone (Abil wax 9801) by Goldschmidt, Cremona (Italy), cyclomethicone (Silicone DC 245) by Dow Corning, Seneffe (Belgium), Ceresine (Ceresine wax SP 252) by Rossow Cosme´tiques, Gennevilliers (France), Mineral Oil was purchased from Carlo Erba, Milano (Italy). Other chemicals and solvents were of reagent grade and were used without further purification. 2.2. Hydrotalcite samples 2.2.1. ZnAl-hydrotalcite synthesis The synthetic hydrotalcite [Zn0.66Al0.34(OH)2] [CO3]0.17 0.5 H2O was prepared by urea method [24]. The corresponding chloride form was obtained by titrating the carbonate form, dispersed in a 1 mol/dm3 NaCl solution (1 g/50 ml), with a 0.1 mol/dm3 HCl by means of an automatic titrator operating at pH stat mode and pH value of 5.0. To perform the Cl =NO 3 exchange 1 g of the chloride form was suspended in 45 ml of a CO2-free aqueous solution 0.5 mol/dm3 of NaNO3 for 24 h. The recovered solid was washed three times with CO2-free deionized water and finally dried over a saturated NaCl solution (relative humidity, R.H., of 75%). It has formula [Zn0.66Al0.34(OH)2] [NO3]0.34 0.6H2O (HTlc-NO3) and ion exchange capacity (IEC) equal to 2.88 meq/g. 2.2.2. HTlc-4BHF synthesis The uptake curve was obtained equilibrating 300 mg of HTlc-NO3 in increasing volumes (3, 5, 8, 10, 13 ml) of 0.2 N 4BHF at pH equal to 8.7. The suspensions were kept under stirring for 3 days at 60 C. The recovered solids were washed three times with CO2-free deionized water and dried at 75% R.H.

2.3.2. Thermogravimetric analyses Thermogravimetric analyses (TGA) and differential thermal analyses (DTA) were carried out using a Stanton-Redcroft STA 780 (England) thermoanalyzer at heating rate of 5 C min1 in air flow to determine the weight loss of water and 4BHF as a function of increasing temperature. 2.3.3. Spectrophotometric analyses The sunscreen content was also confirmed by UV analysis at kmax = 285.0 nm using a spectrophotometer UV–vis Agilent mod 8453 after dissolution of a known amount of intercalation compound in HCl solution and successive dilution with phosphate buffer at pH 7.5. 2.3.4. Chromatographic analyses The amount of Cl, NO 3 counterions in solution, before and after equilibration, was determined by Ion Chromatography using a Dionex 2000 Ion chromatograph equipped with an ionic conductivity detector. 2.3.5. Titrations The Zn and Al content of the hydrotalcite was determined by complexometric titration with standard EDTA solutions after dissolution of a weighed amount of the sample (200 mg) in a few drops of concentrated HCl and successive dilution with water to 100 ml. The chloride form was obtained by means of a Radiometer automatic titrator. 2.3.6. Differential scanning calorimetry (DSC) analyses DSC analyses were performed using an automatic thermal analyser (Mettler Toledo DSC821e, Italy). Temperature calibrations were performed with indium as a standard. Sealed and holed aluminium pans were used for all the samples and an empty pan prepared in the same way was used as a reference. Samples of 3–6 mg were weighted directly into the aluminium pans and thermal

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analyses were conducted at a scanning rate of 10 C/min from 20 to 500 C. 2.3.7. Scanning electron microscopy (SEM) analyses SEM photographs were taken with a Philips SEM 501 (PW 6703, Holland). Before observation, the dried samples were sputtered and coated with gold–palladium, for ca. 5 min under an argon atmosphere. 2.3.8. Intercalated product water-stability Stability of intercalated products in water [25] was performed pouring 100 mg of intercalated products in 50 ml of deionized water. The suspension was stirred for 2 h at room temperature and then centrifuged with a 4236A ALC centrifuge (Milan, Italy) at 4000 rpm for 5 min. The sunscreen content in the supernatant was determined by UV absorption at 285.0 nm. 2.4. Preparation of sunscreen creams The waterproof silicone cream used [26] for the sunscreen formulations had the following composition: 1. polygliceryl-4-isostearate cetyl dimethicone copolyol hexyl laurate (Abil WE-09) 5%, polygliceryl-3-isostearate (Isolan GJ-34) 1%, cyclomethicone (Silicone DC245) 7.50%, cetyl dimethicone (Abil wax 9801) 3%, castor oil 0.50%, ceresin (Ceresine wax SP 252) 1%, mineral oil 2%, 2. 4BHF 2.6% (free or intercalated), 3. deionized water q.b. to 100 g. The components 1 and 3 were mixed at 80 C, cooled down to 60 C, then the immobilizated products (10% in the case of HTlc-d4BHF and 6.95% in the case of HTlcm4BHF) were added; the resulting 4BHF content was 2.6%. Creams containing the same amount of free 4BHF (non-intercalated) were prepared as well. 2.4.1. In vitro 4BHF release from sunscreen creams The sunscreen release was performed in a dissolution apparatus for semisolid preparation (Steroglass, Perugia, Italy) using the Petri disk method [27]. Three hundred milligrams of sunscreen cream were spreaded on the Petri disk (50 mm diameter) with a spatula to produce an even, uniform surface of constant dimensions. The paddle rotation speed was kept at 60 rpm and the dissolution medium volume was 100 ml [28]. The dissolution vessels, closed on the top, were kept in a thermostatically controlled circulation water bath at 32 ± 0.5 C. The dissolution media consisted in deionized water, phosphate buffer pH 5.5 (Farmacopea Ufficiale Italiana XI Ed.) to simulate the skin pH and NaCl solution (0.4 mg/100 ml) [25] in order to simulate the sea water. At predetermined times, 2 ml aliquots were removed, appropriately filtered (13 mm Filter UNIT 0.45 lm NY PP, Lyda, WI, USA), diluted when necessary and analysed by UV at kmax = 285.0 nm. The removed ali-

quots were immediately replaced with the same volume of medium. Tests were performed in sink conditions and in triplicate; the results were recorded as an average. Sunscreen releases from HTlc-4BHF aged formulations were performed. For this reason silicon creams containing intercalated 4BHF were prepared, stored at room temperature and pressure, under light exposure, for a period of six months and the release profiles of all formulations were observed. 2.5. Photochemical and photophysical studies UV–vis absorption spectra of the samples were recorded by a homemade spectrophotometer that uses a DeuteriumHalogen lamp (DH-2000-FHS) as source, a CCD as detector (200–1100 nm range, 2048 pixel, 86 photons/counts) and it is equipped with an integration sphere for reflectance spectra recording. A barium sulphate bar was used as reference to calibrate the spectrophotometer. The spectra were analysed with the Kubelka-Munk equation in order to make possible the comparison. The absorption spectra of the samples were recorded before and after different irradiation times. The solid samples were irradiated by use of a high pressure Mercury lamp, where a band pass filter selected the excitation wavelength of 313 nm. 3. Results and discussion 3.1. Preparation and characterization of the intercalation compounds The nitrate form of HTlc used as precursor host to the sunscreen anions had formula [Zn0.66Al0.34(OH)2](NO3)0.34 Æ 0.6H2O. 4BHF molecule (Fig. 1) contains a sulphonic and a phenolic functionalities that confer to the molecule acidic properties; the pKa values were estimated, by means of 4BHF titration curve to be 2.2 and 8.2, respectively. The distribution diagram of the diprotic acid is a useful tool to establish which species are present at fixed pH values. At relative low pH value (3.9) the mono-anionic form (m-4BHF) is the prevailing species while in an alkaline solution (pH 10.8) the di-anionic form (d-4BHF) prevails. Taking into account these 4BHF properties, several intercalation compounds were prepared, by anion-exchange from the nitrate form. Note that the maximum amount of intercalated anion depends on the charge of the anion: for mono-valent anions is equal to O SO3H HO

OC H3

Fig. 1. Structural formula of 5-benzoyl-4-hydroxy-2-methoxy-benzenesulphonic acid (4BHF).

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the IEC, while for di-valent anions is the half of IEC. Changing the equilibrating solution pH it was possible to have the predominance of different species in solution and so to prepare HTlc containing different amount of 4BHF. Firstly, intercalation compounds containing only mono-valent anion (pH 3.9) or di-valent anion (pH 10.8) were prepared. Successively other intercalation reactions were carried out at intermediate pH values in order to investigate the co-intercalation possibility of mono- and di-valent anions. Table 1 reports the pH of the equilibrating solution and the relative distribution function of m4BHF (am-4BHF), the distribution function of m-4BHF in the solid ( am-4BHF ) and the interlayer distances of the intercalation compounds wet and dried at different R.H. X-ray powder diffraction (XRPD) of samples 1–5 at 75% R.H. revealed different interlayer distances depending on the pH because of the prevailing species present in the solution (Fig. 2). Sample 1, prepared starting from solution having a ˚ am-4BHF equal to 1, had an interlayer distance of 19.4 A that can be assigned to the intercalation of the 4BHF as mono-anion. Sample 2, prepared at 10.8 (am-4BHF = 0) ˚ pH value, exhibited an interlayer distance of 15.3 A ascribed to the intercalation of the 4BHF as di-anion. On the basis of the interlayer distance, it was possible to suppose that samples 4 and 5 contained only the di-anion. The sample 3 deserved a particular attention, in fact, even though the am-4BHF is equal to 1, the XRPD spectrum shows both the m-4BHF and the d-4BHF phases. This pointed out that the solid is more selective towards the d4BHF anions rather than the m-4BHF one and that the second ionization equilibrium of the acid was displaced to favour the d-4BHF. In order to study the selectivity of the hydrotalcite in nitrate form towards the d-4BHF an uptake curve was performed. Weighted amounts of HTlcNO3 were equilibrated in increasing volumes of 0.2 N 4BHF at pH of 8.7. The uptake curve (Fig. 3), obtained reporting uptaken d-4BHF meq/g of HTlc-NO3 vs added d-4BHF meq/g of HTlc-NO3, showed in the first part of the curve that d-4BHF added was almost quantitatively intercalated and that the hydrotalcite had a good affinity towards d-4BHF. Saturation condition was reached when d-4BHF amount in solution was 150% of the ion exchange capacity. Table 2 reports the composition, the exchange Table 1 Composition of the equilibrating solution and of the intercalation compounds and interlayer distance of the solids evaluated under different conditions ˚) Sample Solution Solid Interlayer distance (A

1 2 3 4 5 a b

pH initial am-4BHFa am-4BHF b Wet

75% R.H. P4O10

3.9 10.8 5.2 8.7 9.9

19.4 15.3 19.7–16.6 15.5 15.3

1 0 1 0.16 0.05

1 0 0.4 0 0

19.4 15.3 19.7–16.6 15.5 15.5

19.4 13.3 19.7–16.6 13.3 13.3

am-4BHF molar ratio m-4BHF/m-4BHF + d-4BHF in the solution.  am-4BHF molar ratio m-4BHF/m-4BHF + d-4BHF in the solid.

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Fig. 2. XRPD of the samples 1–5 of Table 1 prepared at the indicated pH values and dried at 75% R.H.

Fig. 3. d-4BHF uptake on [Zn0.66Al0.34(OH)2][NO3]0.34 0.6 H2O (%IEC = 2.88 meq/g) as a function of the amount of d-4BHF added in solution (temperature, 60 C; concentration, 0.2 N).

percentage (express as 100 · eq 4BHF/mol Al) and the UV filter loading (express as 100 · g 4BHF/g HTlc4BHF) of the solids obtained from the uptake curve reported in Table 2. The corresponding XRPD spectrum of sample A (Fig. 4), in which the exchange was equal to ˚ ) and 44.7%, presented two phases: the nitrate phase (9 A ˚ ). As the ion exchange increased the d-4BHF phase (15.3 A the XRPD spectra showed only the d-4BHF phase. It is possible to suppose that the anion exchange mechanism goes on via phase transition until the exchange reached about the 45% of the IEC. Above this value, the nitrate anions were solubilized into the interlayer region of the d-4BHF phase. The intercalation compounds showed a different behaviour to dehydration over P4O10. Owing to the removal of the co-intercalated water, no changes on the interlayer distance were observed for the samples containing the m-4BHF (samples 1 and 3), while a reversible decrease ˚ to 13.3 A ˚ occurred for the samples containing from 15.3 A d-4BHF (samples 2, 4 and 5) (Fig. 5). Other authors [8]

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Table 2 Composition, exchange percentage and loading percentage of the sample of the uptake curve of Fig. 3 Sample

Composition a

HTlc (d-4BHF)0.08(CO3)0.03(NO3)0.12 Æ 0.88H2O HTlc(d-4BHF)0.11(CO3)0.03(NO3)0.06 Æ 0.95H2O HTlc(d-4BHF)0.13(NO3)0.08 Æ 1.08H2O HTlc(d-4BHF)0.13(CO3)0.02(NO3)0.04 Æ 0.99H2O HTlc(d-4BHF)0.13(CO3)0.01(NO3)0.06 Æ 1.1H2O

A B C D E a

% exchange

% loading

44.7 65 76.4 76.4 76.4

16.7 23.7 26.4 26.9 26.5

HTlc = [Zn0.66Al0.34(OH)2].

Fig. 4. XRPD of the samples (A–E) of Table 3 and dried at 75% R.H.

Fig. 5. XRPD of the sample 4: (a) wet, (b) dried at 75% R.H. and (c) dried over P4O10.

˚ phase to the presence, into the interascribed the 15.3 A layer region of the HTlc, of the 4BHF species with an

intermediate ‘‘valence nature’’. The experiments performed ˚ phase is during this work, showed instead that the 15.3 A simply a hydrated phase containing the d-4BHF. The composition of the samples dried at 75% R.H. (Table 3) showed that sunscreen loading can be changed by varying the pH because of the acid–base properties of the 4BHF. The intercalation compounds presented small amounts of nitrate anions not exchanged, evaluated by ion-cromatography, and the samples prepared at pH value higher than 5.2 contained traces of carbonate anions even if the exchange was achieved with CO2-free deionized water and under N2 flow. The sample prepared at pH = 5.2 (sample 3) is clearly biphasic since the XRPD spectrum (Fig. 2) shows the presence of the basal reflections of the HTlc phase loaded with m-4BHF and d-4BHF. Moreover, the X-ray peak of m4BHF phase is more intense than the d-4BHF phase. The composition of sample 3 was obtained from the TGA analysis by simple stoichiometric calculus based on the charge and mass balance. In particular, the charge balance requires that the sum of intercalated anionic charges is 0.34 eq/formula weight, while the mass lost by oxidation (around 400 C) is equal to the sum of the mass of intercalated m-4BHF and d-4BHF. The molar ratio d-4BHF/ m-4BHF was found to be about 1.4, not in agreement with the information obtained from the XRPD spectrum. This apparent discrepancy can be explained assuming that some d-4BHF anions were solubilized in the m-4BHF phase. The intercalation compounds showed a similar thermal behaviour and the coupled TGA–DTA analyses of sample 1, dried at 75% R.H., are reported as an example in Fig. 6. The first endothermic weight loss, until 180 C, was due to the removal of the hydration water, an increase of the temperature up to 500 C gave rise to an exothermic process ascribable to the oxidation of the organic part. In this region the decomposition of the un-exchanged nitrate anions and the condensation of the hydroxyl groups of

Table 3 Composition, exchange percentage and percentage of loading of the samples 1-5 of Table 1 Sample

pH initial 3.9 10.8 5.2 8.7 9.9

1 2 3 4 5 a

HTlc = [Zn0.66Al0.34(OH)2].

Composition a

HTlc (m-4BHF)0.22(NO3)0.12 Æ 1H2O HTlc(d-4BHF)0.12(CO3)0.04(NO3)0.02 Æ 0. 94H2O HTlc(m-4BHF)0.07(d-4BHF)0.1(NO3)0.07 Æ 1.14H2O HTlc(d-4BHF)0.13(CO3)0.02(NO3)0.04 Æ 1.2H2O HTlc(d-4BHF)0.12(CO3)0.03(NO3)0.04 Æ 1.06H2O

% exchange

% loading

67 70.6 79.4 76.4 70.6

37.7 25.6 31.9 26.2 25.1

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Fig. 6. TGA and DTA curves of the sample 1 dried at 75% R.H.

Fig. 7. Differential scanning calorimetry thermogram curves of free 4BHF (a), 4BHF/HTlc-NO3 physical mixture (b), sample 4 dried over P4O10 (c), sample 4 (d) and sample 1 (e).

the sheets also occurred. Between 500 and 700 C was evident a plateau in which zinc and aluminium oxides and zinc sulphate were present. The final weight loss due to the decomposition of the ZnSO4 to ZnO and SO3 occurred at about 800 C. The phases present at 700 C and at 1000 C were identified by XRPD recorded on samples previously calcined at the indicated temperature. The intercalation product samples 1 and sample 4 have been successively submitted to DSC analyses and the ther-

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mograms were compared to those coming from 4BHF and 4BHF/HTlc-NO3 physical mixture (Fig. 7). 4BHF DSC thermogram showed an endothermic peak at ca. 105– 110 C due to the melting point of compound. This peak was present also in the physical mixture thermogram since 4BHF crystalline structure was maintained and its behaviour was independent from hydrotalcite. Sample 1 and 4 thermograms showed the lack of endothermic peak as confirmation of sunscreen intercalation and crystalline structure absence. From the observation of sample 4 thermogram it was possible to note a large peak at 90 C attributable to the intercalated water loss. To confirm this, sample 4 was dried over P4O10 and resubmitted to DSC analysis, after desiccation the peak greatly decreased. On the basis of chemical compositions and interlayer distances, structural models were made. The anions geometry was optimized by applying a Hyperchem MM+ force field. Fig. 8a and b shows the most probable arrangement of the anions m-4BHF and d-4BHF between the HTlc layers respectively. The molecular anions are arranged each other to maximize the p–p interaction between the benzene rings. When the 4BHF was intercalated as mono-anion, the number of the m-4BHF species was equal to the positive charges of the sheets. The model foresees the charge-balancing SO 3 groups lying alternately above and below the layer with the formation of a monolayer of partially interdigitated species. In addition, the plane of the anions containing the benzenic rings is tilted of about 70 with respect the layer plane (Fig. 8a). Differently, the d-4BHF species can interact by the sulphonic and the fenolic group with the positive charges of the faced sheet. The C–S bond is orthogonal to the layer planes and the interlayer distance is determined by the dimension of the 1,4 substituted aromatic ring (Fig. 8b). Samples 1, 2 and 4 have been observed by SEM in order to study the pH effect on crystal morphology (Fig. 9). The acidic conditions (sample 1) were responsible for its crystal fragmentation and no size homogeneity. In fact, the micrographs, shown in Fig. 9 (sample 1), presented two populations; the main population had low size (0.5–1.5 lm) while the minor population presented larger size (5-6 lm). The images of samples 4 and 2 obtained from solutions having 8.7 and 10.8 pH value revealed well formed

Fig. 8. Computer-generated models showing the most probable arrangement of (a) m-4BHF and (b) d-4BHF anions between the HTlc layers.

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Fig. 9. Scanning electron micrographs of samples 1, 4 and 2.

microcrystal in hexagonal form. The former showed 5– 10 lm size, the latter showed larger size (ca. 10–16 lm) and more homogeneous crystals. The same morphology was maintained and no crystal fragmentation occurred also when the intercalation reaction was performed at higher pH condition (10.8). 3.2. Preparation of solar creams and study of sunscreen release The intercalated products have been planned and synthesized in order to prepare semisolid formulations suitable for application to the skin. As these preparations (gels, creams or milks) contain water, the intercalation product water stability was investigated [25]. This test demonstrated that 2.06% and 0.93% 4BHF were released from sample 1 and sample 4 respectively. The deionized water cannot activate the ion-exchange mechanism; however, the presence of CO2 traces should be responsible of the observed releases. Successively many parameters were evaluated to prepare good sunscreen formulations, able to avoid the close contact between 4BHF and skin and being pleasant at the

same time. A waterproof silicone cream [26] was chosen for absence of dissolved ions, water resistance, waterproof and no oily consistences. Among intercalation compounds, 1 (HTlc-m-4BHF, 37.7% sunscreen loading) and 4 (HTlc-d-4BHF, 26.2% sunscreen loading) were chosen and waterproof silicone creams containing the same amount (2.62%) of 4BHF free or intercalated were prepared as previously described. Freshly prepared and six months aged creams were submitted to in vitro release studies in three dissolution media, as shown in Figs. 10a–c, and monitored for 8 h. Each test was performed in triplicate; confidence intervals, calculated for n = 3 at a = 0.05 significance level, resulted always within ±8.5%. Errors bars have been calculated but are not reported in Fig. 10 for graph clarity as they may be confusing since many profiles of them overlap. In deionized and sea water media (Fig. 10 a and b) the sunscreen release from formulations containing intercalated 4BHF was negligible, also for aged creams, while it reached 18.5% (a) and 12.4–28.3% (b) from formulations containing free 4BHF. Differently, in phosphate buffer pH 5.5 (c) the percent release increased but it was lower than that are from free

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4BHF formulations. In this medium the better result was shown by aged cream containing sample 4. The higher sunscreen release in the case of phosphate buffer demonstrated that the phosphate anions can penetrate into the creams decreasing their water resistance. These anions can reach HTlc-4BHF and induce the ionexchange, responsible for 4BHF sunscreen release from interlayer spaces, in a more quickly manner in freshly prepared creams than aged. Perhaps, during the storage some interactions between lipophylic ingredients and intercalation products could occur giving rise to a lipophylic microenvironment suitable to protect the intercalation product and to reduce the contact with phosphate anions. It is noteworthy to underline that sample 4 profile release was always lower than sample 1 (freshly prepared and aged creams) because in this case the sunscreen is more linked to HTlc structure and needed more time to break the bonds and to leave the interlayer spaces. Moreover pH 5.5 release profiles did not void the proposed strategy because:

Fig. 10. Sunscreen release from creams in water (a), in sea water (c) and in phosphate buffer pH 5.5 (c).

1. phosphate buffer in vitro conditions, reproducing skin pH value, did not reproduce the real physiological conditions; 2. the tests were carried out for very prolonged time (8 h) in comparison to real use; generally the solar product application is repeated every 2 or 3 h.

Fig. 11. Absorption spectra of sample 1 (a), sample 4 (b) and corresponding creams containing sample 1 (c) and sample 4 (d) recorded before and after 30 min, 90 min and 240 min of irradiation (kexc = 313 nm).

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3.3. Photophysical and photochemical studies Fig. 11 reports the UV-vis absorption spectra of sunscreen intercalation products and of their formulations in order to evaluate their protection range and the photostability. Sample 1 presented a broad absorption band centered at 350 nm, while compound 4 had a more structured absorption with the main maximum peak at 390 nm and a shoulder at 320 nm. These data showed that the chromophore, when was in the di-anion form, had a spectrum more shifted to the visible region likely due to the charge conjugation effect. However its capacity to filter the UV-A and UVB regions was not reduced since both samples had similar absorption intensities in the above range. This observation indicated that sample 4 had a broader protection range. The photochemical stability of the intercalation compounds had been qualitatively checked by spectrophotometric analysis once the samples were irradiated. For sample 1, the spectra recorded at different irradiation times (Fig. 11a) did not reveal significant spectral changes. These findings allowed to consider the intercalation compound photochemically stable, at least in the present experimental conditions, suggesting that the intercalation of 4BHF derivative in hydrotalcites leads to an improvement of its photostability compare to that of the sunscreen alone (solution or solid state) which degrades quite efficiently upon irradiation (data not shown) in agreement with literature data [29–31]. On the other hand, the effect of hydrotalcites to increase the photochemical stability of sunscreens was previously observed [6]. In the case of sample 4, spectral changes have been observed after prolonged irradiation, since the spectrum decreased in intensity only after 240 min of exposition. This behaviour indicated that the intercalation compound, containing the chromophore in di-anion form, is slightly less stable than sample 1. The spectrophotometric characterization carried out on the intercalation compounds had been extended to their formulations. For both samples (1 and 4) the dispersion in the cream did not alter their spectral features (Fig. 11c and d) and hence their protection properties. The small broadening of the spectra in the blue-edge is probably due to the contribution of the cream constituents. The spectra recorded at different irradiation times on the formulation containing sample 1 indicated that degradation processes might occur only for long exposition since after 240 min a decrease in the absorption intensity was detected. It is noteworthy to point out that the slight absorbance increase at short irradiation times is probably due to the evaporation processes of components present in the cream. On the other hand the formulation containing sample 4 appeared photochemically stable since no spectral changes were observed upon irradiation. 4. Conclusions Taking into account the improved photostability of 4BHF, when intercalated between HTlc lamellae, it is pos-

sible to underline that this anionic clay is suitable for solar cosmetic products. The 4BHF storage into layered double hydroxide permitted a reduction of sunscreen release avoiding its direct contact and penetration in the skin, preventing thus cutaneous reactions and allergy problems that may occur. It is noteworthy to underline that the good results obtained from freshly prepared creams whose characteristics remained or improved during ageing, showed that HTlc plays an important protective role during the product storage too. Acknowledgment The authors are very grateful to Mr. Marco Marani for the precious collaboration and technical assistance. References [1] National Institute of Health Consensus Statement Online. Sunlight, Ultraviolet Radiation and Skin. 7 (1989) 1. [2] M. Sugiura, R. Hayakawa, Z. Xie, K. Sugiura, K. Hiramoto, M. Shamoto, Photoderm. Photoimm. Photomed. 18 (2002) 82. [3] L. Matthieu, L. Meuleman, E. Van Hecke, A. Blondeel, B. Dezfoulian, L. Constandt, A. Goossens, Cont. Derm. 50 (2004) 238. [4] C.J. Le Coz, A. Bottlaender, J. Scrivener, F. Santinelli, B.J. Cribier, E. Heid, E. Grosshans, Cont. Derm. 38 (1998) 245. [5] C. Rossi, A. Schoubben, M. Ricci, L. Perioli, V. Ambrogi, L. Latterini, G.G. Aloisi, A. Rossi, Int. J. Pharm. 295 (2005) 47. [6] L. Perioli, V. Ambrogi, B. Bertini, M. Ricci, M. Nocchetti, L. Latterini, C. Rossi, Eur. J. Pharm. Biopharm. 62 (2006) 185. [7] L. Perioli, V. Ambrogi, C. Rossi, L. Latterini, M. Nocchetti, U. Costantino, J. Phys. Chem. Solids 67 (2006) 1079. [8] K.R. Franklin, E. Lee, C.C. Nunn, J. Mater. Chem. 5 (1995) 565. [9] Q. He, S. Yin, T. Sato, J. Phys. Chem. Solids 65 (2004) 395. [10] T. Pigot, T. Arbitre, H. Martinez, S. Lacombe, Tetrahedron Lett. 45 (2004) 4047. [11] A.M. El–Toni, S. Yin, T. Sato, Mater. Chem. Phys. 89 (2005) 154. [12] F. Trifiro`, A. Vaccari, in: G. Alberti, T. Bein (Eds.), Hydrotalcite-like Anionic Clays (Layered Double Hydroxides), Comprehensive Supramolecular Chemistry, vol. 7, Pergamon, Elsevier Science, Oxford, 1996, p. 251. [13] V. Rives, M.A. Ulibarri, Coord. Chem. Rev. 181 (1999) 61. [14] V. Rives (Ed.), Layered Double Hydroxides: Present and Future, Nova Science Publishers, Inc., New York, 2001. [15] A.I. Khan, D. O’Hare, J. Mater. Chem. 12 (2002) 3191. [16] A. de Roy, C. Forano, J.P. Besse, in: V. Rives (Ed.), Layered Double Hydroxides: Present and Future, Layered Double Hydroxides and their Intercalation Compounds in Photochemistry and Medicinal Chemistry, Nova Science Publishers, Inc., New York, 2001, p. 1 (Chapter 1). [17] F. Leroux, C. Taviot-Gue´ho, J. Mater. Chem. 15 (2005) 3628. [18] J. Rocha, M. del Arco, V. Rives, M.A. Ulibarri, J. Mater. Chem. 9 (1999) 2499. [19] U. Costantino, M. Nocchetti, in: V. Rives (Ed.), Layered Double Hydroxides: Present and Future, Layered Double Hydroxides and their Intercalation Compounds in Photochemistry and Medicinal Chemistry, Nova Science Publishers, Inc., New York, 2001, p. 383 (Chapter 8). [20] L. Latterini, M. Nocchetti, U. Costantino, G.G. Aloisi, F. Elisei, Inorg. Chim. Acta. 360 (2007) 728. [21] V. Ambrogi, G. Fardella, G. Grandolini, L. Perioli, Int. J. Pharm. 220 (2001) 23.

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