Multiparticulate carriers for sun-screening agents

International Journal of Cosmetic Science, 2010, 32, 89 98 doi: 10.1111/j.1468-2494.2010.00547.x Review Article Multiparticulate carriers for sun-screening agents S. K. Jain* and N. K. Jain *SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur-495 009, Chhattisgarh, India and Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar-470 003, Madhya Pradesh, India Received 8 October 2008, Accepted 30 April 2009 Keywords: advantages, applications, microspheres, multiparticulate carriers, sunscreens Synopsis Many molecular sunscreens penetrate into the skin causing photo-allergic and photo-toxic reactions as well as skin irritations establishing an urgent need for the development of a safer sunscreen formulation. The search for active substances, efficient combinations, and the design of novel vehicles or carriers has led to the implementation of new cosmetic systems in contrast to the classic forms such as creams or gels. Amongst various approaches utilized to improve performance of sunscreening agents, the use of multiparticulate delivery systems is gaining increasing attention amongst researchers. Multiparticulate delivery systems can be incorporated into gels, creams, liquids, powders or other formulations, and can release active agents depending on their temperature, moisture, friction, volatility of the entrapped ingredients or time. These systems also have the ability of scattering or reflecting incoming UV radiations and therefore can act as physical sunscreens on their own. Résumé Beaucoup de filtres solaires pénètrent à l état moléculaire dans la peau provoquant des réactions photo-allergiques et photo-toxiques ainsi que des irritations ce qui nécessite un développement urgent de formulation solaire plus sûre. La recherche de substances actives, des mélanges efficaces Correspondence: Sunil K. Jain, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur-495 009, Chhattisgarh, India. Tel.: +91 775 226 0027; fax: +91 775 226 0148; e-mail: suniljain25in@yahoo.com et la conception de nouveaux véhicules ou de transporteurs a abouti à la mise en œuvre de nouveaux systèmes cosmétiques face aux formules classiques que sont des crèmes ou des gels. Parmi ces diverses approches utilisées pour améliorer la performance des filtres solaires, l utilisation de systèmes multi particulaires de délivrance suscite un intérêt croissant parmi les chercheurs. Ces systèmes multi particulaires peuvent être incorporés à des gels, des crèmes, des liquides, des poudres ou d autres formulations et peuvent libérer des agents actifs en fonction du temps, ou selon la température, l humidité, la friction, ou la volatilité des ingrédients encapsulés. Ces systèmes ont aussi la capacité de disperser ou de refléter les radiations UV et peuvent donc agir à eux seuls comme des filtres solaires physiques. Introduction Sunscreen is a lotion, spray or other topical product that is supposed to protect the skin from the sun s ultraviolet (UV) radiation. The most effective sunscreen can protect against UV-A (near UV radiation; wavelength between 320 and 400 nm), UV-B (UV radiation, wavelength between 280 and 320 nm) and UV-C (far UV radiation, wavelength between 200 and 280 nm) radiations (Fig. 1). The UV-A radiation penetrates into the skin and reaches the dermis; provoking several damages such as immediate and delayed tanning reactions, loss of collagen, diminution in the quantity of blood vessels, alteration of the connective tissue of the dermis and skin photosensitization. In the UV-A range, melanin and haemoglobin are the 89

Figure 1 Penetration of different wavelengths of light into human skin. main absorbers. The UV-B region is responsible for the tanning and immediate damage to the skin, which results in erythema or sunburn [1]. Although the UV-C region has desirable properties such as germicidal activity, this spectral band also has been reported to be erythemogenic, mutagenic and carcinogenic [2]. Ultraviolet-induced photoageing accounts for 80 90% of visible skin ageing [3]. Ultraviolet absorbing organic sunscreens may penetrate the skin and their UV radiation absorbing characteristics make them potential candidates with photodynamic activity. Although sunscreen does reduce sunburn and other skin damages, the use of sunscreen causes an increased risk of melanoma. It is estimated that the incidence of nonmelanoma skin cancer in the United States exceeds one million cases per year. Epidemiological studies have shown repeatedly that the sunscreen-user has a higher risk of skin cancer than the non-user [4, 5]. Ultraviolet radiation damages the skin by both direct effects on DNA and indirectly on the skin s immune system. In animal models, sunscreens prevent the formation of squamous cell carcinomas of the skin. Because of increase in the number of skin cancers diagnosed annually and recognition of adverse effects of UV radiation, several public education programmes have been undertaken concerning photo-protection, including the use of sunscreens. Most sunscreens contain either an organic chemical compound that absorbs UV light (such as oxybenzone) or an opaque material that reflects light (such as titanium dioxide, zinc oxide) or a combination of both. Typically, absorptive materials are referred to as chemical blockers; whereas opaque materials are mineral, called physical blockers. It is believed that the increased use of chemical sunscreens is the primary cause of the melanoma epidemic [6]. A wide variety of different creams, dispersions, emulsions, gels, ointments, lotions, milks, sprays, tonics and hydrogels are available in the market using a variety of UV-filter systems. Many products contain broad spectrum (UV-A and UV-B) sunscreening agents with a moderate sun protection factor (SPF). A sunscreen product must have a minimum SPF of less than the number of active sunscreen ingredients used in combination multiplied by 2. Products with SPF values above 30 are allowed, but the SPF declaration for sunscreen with SPF values above 30 is limited to SPF 30 plus [7]. In daily life, UV exposure is unavoidable, therefore sunscreen should be used regularly [8]. The regular use of sunscreens has been shown to reduce the number of actinic or percutaneous keratosis and solar elastosis. Sunscreens also prevent immuno-suppression. Over long term and frequent use, particular attention has to be paid to their efficacy and safety. The photo-degradation of sun filter molecule produces sub-molecules that are potentially dangerous for the skin as they induce sensitization and skin irritation. Several techniques are available to reduce photo-degradation: (i) different sun filters can be used in same product, so that a synergistic effect is obtained, (ii) specific sun filters that are stable at specific wavelength can be used and (iii) the sun filter molecule can be protected by complexing or encapsulating it with specific substances. This process protects the filter molecule from radiation so that the interactions are reduced or eliminated. As a result of the reduction of the ozone layer, there is an increasing need of effective UV protection systems with simultaneously minimized side-effects. Therefore, there is an urgent need for the development of safer sunscreens system [9]. The ideal sunscreen agent should have the following properties [10]: i. Should absorb light preferentially over the range of 280 320 nm, ii. Should be stable to heat, light and perspiration, iii. Should be non-toxic and non-irritant, iv. Should not be rapidly absorbed, v. Should be neutral and vi. Should be readily soluble in suitable vehicles. 90 International Journal of Cosmetic Science, 32, 89 98

Sunscreens Chemical sunscreens Certain chemical compounds are able to interact with UV light, diffusing its damaging energy. The chemical bonds in these molecules can absorb UV light and remit or reabsorb it in a harmless form. Typically these chemicals are aromatic compounds that have a carbonyl group. In general, they also have an electron releasing group such as an amine or a methoxyl group in either the ortho- or para-position on the aromatic ring. When UV light strikes one of these molecules, it causes a photochemical excitation and the molecule is stimulated to a higher energy level. When the molecule returns to its original energy state, the excess absorbed energy is emitted as light with a different energy state. These sunscreens emit energy in the infrared region and may cause an extremely small heating effect on the skin. Others emit the energy in the range of visible light. In fact, products that use these types of compounds give the skin a slight bluish tinge. Each sunscreen molecule can repeat this absorption-emission cycle multiple times before it decays. A variety of compounds, which have molecular structure capable of UV-B absorption, have been developed. This absorber can be formulated in appropriate vehicles that can be easily applied to exposed skin to protect cells from interaction with radiation. Today, however, virtually all types of topical products from moisturizers to shampoos include organic sunscreen. There are potential difficulties associated with long term use of organic sunscreens such as allergy and toxicity. These chemical screens give off free radicals as they absorb photons, allowing a degree of secondary injury or damage possibly to collagen or elastin or DNA. Increased daily exposure to these chemicals will probably result in the incidence of adverse reactions that must be taken into account [11]. Chemical sunscreens act by absorbing the UV rays that hit them and thereby absorbing the radiation. These sun filters are formulated with other compounds to obtain highly effective products with protection factors varying from 4 to 30. Importantly, often they have to be repeated quite frequently. Chemical sunscreens can be classified based on the substances they are derived from i.e., p-aminobenzoates, salicylates, cinnamates, benzophenones, anthranilates, dibenzoylmethanes, camphor derivatives and other miscellaneous chemicals [12]. Chemical sunscreens are sometimes preferred over physical sunscreens because they are often completely colourless and odourless. Physical sunscreens Physical sunscreens contain extremely fine particles of minerals such as zinc oxide, titanium dioxide, kaolin, barium sulphate, mica and iron oxide that stay on the skin s surface, creating a barrier that reflects the sun rays. The most common type used is ultrafine titanium dioxide (TiO 2 ), made up of minute particles, 20 30 nm in size. These products have advantages over chemical sunscreens in that they are inert substances that do not break down over time and are rarely associated with allergic reactions. They are far less liable to cause skin irritation, being in the form of insoluble particles that are not absorbed through the skin. Because of the small size of the particles, modern physical sunscreens reflect radiation in the UV-B and short UV-A regions better than earlier products. Their sunscreen properties can be attributed to several factors such as particle size, number of particles (concentration), crystalline form, refraction index, dispersion media and semiconductor properties [13]. However, there are indications that the very small TiO 2 particles (e.g. 5 20 nm) penetrate into the skin and may interact with the immune system [14]. Herbal sunscreens As compared with physical and chemical sunscreens, herbal products are mild, biodegradable, and have low toxicity profile [15]. The Indian aloe (Aloe barbadensis), more commonly known as the aloe vera, is a good sunscreen while going out on the beach. Its paste must be applied on the skin before going out into the sun. It is a natural barricade to the harmful rays of the sun. Sandalwood, known for its cooling properties, is an herbal sunscreen. Its paste is applied on the skin. However, the paste is generally diluted because it becomes too thick and stretches uncomfortably on the skin. Rice bran oil has some anti-oxidizing as well as sunscreen properties and is used in sunscreen products and hair conditioners. Green tea (Camelia olifera) contains polyphenols. When ingested, these polyphenols help protect the skin against damage from the UV radiation that causes sunburn [16]. International Journal of Cosmetic Science, 32, 89 98 91

Ocimum sanctum also contains polyphenols/flavonoids that can be effectively incorporated in cosmetic preparations as a potent sunscreen agent. Some of the other herbal sunscreens reported in literature include Grapes (Vitis vinifera) and rhatany (Krameria triandra) extract. Table I lists the most common chemical, physical and herbal sunscreening agents [10, 16]. Multiparticulate delivery systems of sunscreening agents Encapsulation is a process by which very thin coatings of inert natural or synthetic polymeric materials are deposited around fine particles of solids or droplets of liquids. Products thus formed are known as multiparticulate delivery systems [7]. An encapsulated system consists of a particle totally surrounded by a matrix (Fig. 2). In this case the particle, theoretically, is totally isolated from its surroundings. There are number of reasons why encapsulation is important for sunscreening agents. Different components can be separated, avoiding incompatibility, if any. Undesired properties of the active sunscreening agent such as contact and photo-contact allergic dermatitis can be masked. Encapsulation converts the organic sunscreen into particulates and isolates the sunscreen from skin and minimal ingredient interaction, if any; if it is properly designed. Encapsulation also allows the use of the oil soluble actives in oil-free systems with a greater range of solubility [17]. Finally, encapsulation produces a External Water Phase Matrix Organic Sunscreen Molecule Figure 2 Schematic presentation of microspheres containing a sunscreening agent. delivery system that decreases the amount of organic active needed and still maintains its efficacy. The ability to vary physical properties and the surface chemical properties through the manipulation of matrix composition can provide much greater flexibility when incorporating organic sunscreens even in to the most difficult formulations, whether new or existing [18, 19]. The objectives of carriers systems of sunscreens are: i. To reduce contact and photo-contact allergic dermatitis and skin irritation, if any; ii. To reduce free drug concentration of sunscreening agent over the skin; iii. To enhance the photo stability of sunscreening agent; Table I Various chemical, physical and herbal sunscreening agents S. No. Type 1. Chemical UV-A absorbers UV-B absorbers Oxybenzone; Sulisobenzone; Dioxybenzone; Methyl anthranilate; Avobenzone; Terephatylidene dicamphor sulphonic acid; Bis-ethylhexyloxyphenol methoxyphenyl triazine, Bis-Ethylhexyloxyphenol; Methoxy phenyl triazoeno Para-amino benzoic acid; p-amyl dimethyl para-amino benzoic acid (padimate A); 2-Ethoxyethyl-p-methoxycinnamate; Digalloyl trioleate; Ethyl 4-bishydroxypropyl aminobenzone; 2-Ethoxyethyl 2-cyano-3,3-diphenylacrylate; 2-Ethylhexyl-p-methoxy cinnamate; 2- Ethylhexyl salicylate; Glyceryl para-amino benzoic acid; Homo methyl salicylate; Dihydroxyacetone; Octyl dimethyl para-amino benzoic acid (padimate O); 2-Phenylbenzimidazole-5-sulphonic acid; Triethanolamine salicylate 2. Physical Titanium dioxide; Zinc oxide; Red petrolatum 3. Herbal Aloe (Aloe barbadensis); Calendula (Calendula officinalis); Grapes (Vitis vinifera) extract; Rhatany (Krameria triandra) extract; Green tea (Camelia olifera) extract 92 International Journal of Cosmetic Science, 32, 89 98

iv. To reduce the penetration of sunscreening agent and photo-degradation products through skin; v. To reduce the dose of sunscreening agent and vi. To increase the sunscreen efficiency. Multiparticulate delivery systems were envisaged mainly as site specific drug delivery systems because they present several advantages: (i) good photo stability, when applied on the skin, (ii) easy preparation with a defined size in a narrow size distribution, (iii) protection of the active incorporated, (iv) controlled release of the actives, (v) homogeneous skin distribution and (vi) the possibility of incorporating either lipophilic or hydrophilic actives [20]. These systems can be incorporated into gels, creams, liquids, powders or other formulations, and can release actives depending on their temperature, moisture, friction, volatility of the entrapped ingredients, or time [21]. As sunscreen preparations are often applied on large skin areas, even low penetration rates can cause significant amount of chemical UV absorber to enter the body. Therefore, sun-protecting preparations need to achieve a controlled release. For this purpose, microspheres have been used. In addition, it has been found that microspheres also act as physical sunscreens on their own, i.e. they have the ability of scattering or reflecting incoming UV radiations [22]. Solid lipid nanoparticles (SLN) are introduced as the new generation of carriers for cosmetics, especially for UV blockers, for the use on human skin and/or hair [23]. A brief review of various multiparticulate carriers used for sunscreening agents are as follows. oxybenzone. The spherical, smooth and crosslinked surface of microsphere formulation is clearly evident in scanning electron photomicrograph (Fig. 3). The formulation containing oxybenzone bearing gelatin microspheres in aloe vera gel showed best sunscreen efficacy. The results of this study emphasize the potential of gelatin microspheres as a new topical drug delivery system for enhancing the sunscreening efficacy of oxybenzone. In another study, PMMA microspheres of EHM were prepared using emulsion solvent evaporation method to improve its photo stability and effectiveness as sunscreen. The cream base formulations containing EHM loaded microspheres showed better SPF (>16.0) as compared with formulation that contained 3% free EHM as sunscreen agent and had shown SPF of 4.66. The topical application of cream formulation containing PMMA microspheres of EHM may be more efficient in protecting against UV-induced erythema probably as a result of the microsphere film formation over the skin, which itself acts as a physical barrier against the UV radiations. These studies revealed that the incorporation of EHM loaded PMMA microspheres into cream base had greatly increased the efficacy of sunscreen formulation (approximately four times). Yener et al. [22] prepared solid lipid microspheres (SLM) of octylmethoxycinnamate (OMC) to achieve controlled release penetration of OMC from skin and to improve its photo stability. The rate of penetration was found to be significantly dependent upon the formulation and could be decreased by up to 77% in SLM formulations. Microparticles Microspheres are homogeneous particles wherein the cosmetic ingredients are dissolved or dispersed throughout the polymer matrix [15, 19, 24]. Our research group developed and evaluated gelatin microspheres of oxybenzone and polymethylmethacrylate (PMMA) microspheres of ethylhexyl methoxycinnamate (EHM) to enhance their sunscreening efficacy [17, 25]. The gelatin microspheres of oxybenzone were prepared using emulsification method. Oxybenzone is insoluble in water and hence difficult to be incorporated in cream base but after entrapment in microspheres, it could be easily incorporated in to cream base without any crystallization problem, common with Figure 3 Scanning electron photomicrograph of gelatin microspheres of oxybenzone. International Journal of Cosmetic Science, 32, 89 98 93

When different topical vehicles were compared, OMC was released and penetrated into rat skin more quickly and in greater amount from vehicles containing free OMC than in SLM form. In addition, photo stability was shown to be improved in SLM form. Solid lipid microparticles loaded with the sunscreen agent, octyl-dimethylaminobenzoate (ODAB) was prepared to achieve enhanced sunscreen photo stability [26]. The microparticles were produced by the melt dispersion technique using glyceryl behenate as lipid material and Poloxamer 188 (Spectrum Chemicals, Gardena, CA, USA) as the emulsifier. The release of sunscreening agent from the microparticles was slower than its dissolution rate and the photo-decomposition of ODAB was markedly decreased (>51.3%) by encapsulation into the lipid microparticles. The efficacy of the SLM carrier system was also evaluated after its introduction in model topical formulations, i.e., hydrogel and o/w emulsion. Furthermore, in vitro release measurements performed using Franz diffusion cells with polycarbonate membranes indicated that the retention capacity of the microparticles was lost after their incorporation into the emulsion whereas it was retained in the hydrogel. Moreover, the microparticles achieved a reduction of the sunscreen photodegradation in the hydrogel vehicle (the ODAB loss decreased from 87.4% to 59.1%) whereas no significant photo-protective effect was observed in the emulsion. Lemperle et al. [27] administered PMMA microspheres intradermally and subdermally into the abdominal skin of rats and found that PMMA might be applied in the form of microspheres in corneum and subcutis of human patients with wrinkles or acne scars without causing biological degradation or cancer. These microspheres were able to remain on the skin for longer period of time and, as a consequence, they were able to prolong release of vitamin A. Lipid microparticles loaded with free butyl methoxydibenzoylmethane (BMDBM) or its complex with hydroxypropyl-beta-cyclodextrin (HP-b-CD) were prepared using tristearin as the lipid material and hydrogenated phosphatidylcholine as the emulsifier [28]. Release of BMDBM from the lipospheres was lower when it was incorporated as inclusion complex rather than as free molecule. Unencapsulated BMDBM, its complex with HP-b-CD, the sunscreen-loaded lipospheres or the lipoparticles containing the BMDBM/HP-b-CD complex, were introduced into a model cream (o/w emulsion) and irradiated with a solar simulator. The photo-degradation studies showed that all the examined systems achieved a significant reduction in the light-induced decomposition of the free sunscreening agent (the BMDBM loss decreased from 28.9% to 17.3%). However, photolysis experiments performed during 3 months storage of the formulations demonstrated that the photo-protective properties of the HP-b-CD complex and of BMDBM alone-loaded lipospheres decreased over time whereas the microencapsulated HP-b-CD/ BMDBM complex retained its photo-stabilization efficacy. Fairhurst and Mitchnick [18] investigated the use of microcapsules for increasing the SPF in sunscreen formulations without encountering problems of sunscreen solubility or skin sensitivity. New technologically improved microencapsulated sunscreens characterized by UV radiation stability had shown good substantivity, low toxicity, better tolerability and ease of formulation [29]. Nanoparticles Nanoparticles are novel delivery system for pharmaceutical and cosmetic active ingredients [30]. The solid lipid nanoparticles (SLNs) and vehicles thereof known as nanostructurated lipid carriers (NLCs), wherein the solid lipid phase of these nanoparticles has been loaded with liquid lipids, i.e. oils, have attracted the attention as novel delivery systems for organic and inorganic sunscreens [9, 31, 32]. The advantage of these vehicles over the polymeric particles lies in the compounds used in their manufacture, because they are mainly constituted by physiological compounds and do not require the use of organic solvents for their preparation [33]. Surprisingly, it was discovered that highly crystalline SLNs could also act as particulate UV blockers by scattering light efficiently [23]. It was found that incorporation of the molecular sunscreen into the SLN matrix lead to a synergistic protective effect, i.e. the measured UV absorption was higher than the theoretically calculated values from the single effects of the molecular sunscreen and the particle dispersion itself [33]. Zulli et al. [34] encapsulated Uvinil T 150 (UV-B filter) (E Merck, Darmstadt, Germany) (into lipid nanoparticles. They observed an almost 100-fold higher affinity of Uvinil T 150 to hair from positively charged compared with negatively charged particles. Nanospheres containing beta carotene and a 94 International Journal of Cosmetic Science, 32, 89 98

blend of UV-A and UV-B sun filters were prepared by Olivier-Terras [35]. The results clearly showed the synergistic effect resulting from the combination of nanospheres and filters. Conventional o/w emulsion and highly crystalline lipid nanoparticles (CLN) of the molecular sunscreen benzophenone-3 were prepared and the efficacy of two different carrier systems was compared by Wissing and Muller [9]. It was observed that CLN acted as physical sunscreen themselves and showed improved photo protection compared with a placebo emulsion with the same lipid content. Incorporation of a molecular sunscreening agent further improved the protection level in a synergistic way. The crystalline cetyl palmitate SLN particles had the ability of reflecting and scattering UV radiation on their own thus leading to photo protection without the need for molecular sunscreens. An in vitro assay showed that a placebo cetyl palmitate SLN formulation was two to three times potent in absorbing UV radiation than a conventional emulsion. Incorporation of sunscreens into SLN leads to a synergistic photo protection, i.e. higher than the additive effect of UV scattering caused by the SLN and UV absorption by the sunscreen [36]. Experiments with SLN have reported increased UV absorption of the molecular sunscreen 2-hydroxy-4-methoxybenzophenone and tocopherol acetate in a range between 280 nm and 400 nm after its incorporation into SLNs made up of high crystalline cetyl palmitate. In the case of NLCs, decyl oleate carnauba wax loaded nanoparticles had demonstrated improved sun protection factor of TiO 2 in aqueous media without the use of complex formulations [36, 37]. It is reported that the photo stability of sunscreening agent encapsulated in b-cyclodextrin is significantly higher than that of the same agent uncomplexed or complexed with phospholipids [38]. Alvarez-Roman et al. [39] prepared biodegradable polymeric nanoparticles containing lipophilic sunscreen OMC by solvent displacement method. They investigated the influence of Polysorbate-85 (Spectrum Chemicals, Gardena, CA, USA) and Poloxamer 188 as stabilizing agents, OMC loading capacity and the photo-protective potential of the designed formulations. The OMC-nanoparticles provided partial protection against UV-induced erythema in a manner significantly better than a conventional gel. Polymeric nanoparticles composed of fatty acids and polyvinylalcohol for topical application of oxybenzone were prepared using a solvent extraction method [40]. Titanium dioxide nanoparticles were formed by reaction of an inorganic titanium compound with water or ice to form an aqueous titanium compound that was reacted with a dispersing agent. These nanoparticles were precipitated to form a suspension. The size of the nanoparticles can be controlled by selecting the ratio of titanium to dispersing agent. These nanoparticles can be used in suspension or powder form [41]. Perugini et al. [42] investigated the influence of nanoparticlesbased systems on the light-induced decomposition of the sunscreen agent, trans-2-ethylhexyl-p-methoxycinnamate (trans-ehmc). Ethylcellulose (EC) and poly-d,l-lactide-co-glycolide (PLGA) were used as biocompatible polymers for the preparation of the particulate systems. The salting out method was used for nanoparticles preparation and several variables were evaluated to optimize product characteristics. The photo-degradation of the sunscreen agent in emulsion vehicles was reduced by encapsulation into the PLGA nanoparticles (the extent of degradation was 35.3% for the sunscreen-loaded nanoparticles as against 52.3% for free trans- EHMC) whereas the EC nanoparticle system exhibited no significant effect. Therefore, PLGA nanoparticles loaded with trans-ehmc may improve the photo stability of the sunscreen agent. Different nanocapsules (NCs) made of poly-n-caprolactone (PCL) containing the lipophilic OMC were developed and characterized for their sunscreening efficacy by Jimenez et al. [43]. The PCL nanoparticles loaded with OMC were effective in reducing light-induced degradation of the sunscreen agent. One of the sunscreens available in market based on nanoparticles is Olay Moisturizers (Proctor and Gamble, Cincinnati, OH, USA) that contains transparent nano zinc oxide particles for better UV protection. Microsponge delivery system A patented microsponge delivery system (MDS) is highly cross-linked, porous, polymeric microspheres systems consisting of porous microspheres that can entrap wide range of actives and subsequently release them onto the skin over a time and in response to a trigger [44]. It is a unique technology for the controlled release of topical agents and consists of microporous beads, typically 10 25 lm in diameter, loaded with active agent. When applied to the skin, the MDS releases its active ingredient on a time mode and also in response to other stimuli (rubbing, temperature, International Journal of Cosmetic Science, 32, 89 98 95

Table II Patents related to multiparticulate delivery systems of sunscreening agents S. No. Patent No. Title Reference 1. US 20080019929 Micro-particulate UV absorber composition [48] 2. US 20087326399 Titanium dioxide nanoparticles and nanoparticle suspensions and [41] methods of making the same 3. WO/2007/002744 Aluminium phosphate based microspheres [49] 4. WO/2007/038404 Cosmetic composition containing thermoplastic microspheres and skin [50] beneficial agents 5. EP1506772 Aesthetically and SPF improved UV sunscreens comprising glass [51] microspheres 6. EP1600210 Charged microspheres [52] 7. WO/2002/041987 Polymeric microspheres [53] 8. US 6391288 Microcapsule and method of making the same [54] 9. US 6242099 Microcapsules made of chitin or of chitin derivatives containing a [55] hydrophobic substance, in particular a sunscreen, and process for the preparation of such microcapsules 10. US 6261713 Delivery system for inorganic sunscreens [56] 11. US 6303149 Method for the preparation of oxide microcapsules loaded with [57] functional molecules and the products obtained thereof 12. US 6036945 Delivery systems for active ingredients including sunscreen actives [58] and methods of making same 13. US 5961990 Cosmetic particulate gel delivery system and method of preparing complex gel particles [59] SPF, sun protection factor. ph etc). By delivering the active gradually to the skin, MDS-benzoyl peroxide formulations have excellent efficacy with minimal irritation [44]. Microsponge delivery system technology is being used in cosmetics, over-the-counter skin care, sunscreens and prescription products. Delivery system comprised of a polymeric bead having network of pores with an active ingredient held within was developed to provide controlled release of the active ingredient(s) whose final target is skin itself [45]. The system was employed for the improvement of performance of topically applied drugs [44, 46, 47]. The MDS has advantages over other technologies like microencapsulation and liposomes. Microcapsules cannot usually control the release rate of actives. Once the wall is ruptured the actives contained within microcapsules will be released. Liposomes suffer from lower payload, difficult formulation, limited chemical stability and microbial instability. Although microsponge system, in contrast to the above systems, is stable over range of ph 1 11, temperature up to 130 C; compatible with most vehicles and ingredients; self sterilizing (average pore size is 0.25 lm where bacteria cannot penetrate); higher payload (50 60%), still free flowing and can be cost effective. Microsponge delivery system can be incorporated into conventional dosage forms such as creams, lotions, gels, ointments and powders. The MDS provides long lasting product efficacy with improved protection against sunburns and sun related injuries even at elevated concentration and with reduced irritancy and sensitization. The patents related to various delivery systems of sunscreen are listed in Table II. Summary The multiparticulate delivery systems facilitate the formulation of high efficiency sunscreen and offer the advantages of overcoming solubility, photodegradation and skin irritancy problem. These systems can be incorporated into gels, creams, liquids, ointments that release sunscreen depending on their temperature, moisture, friction, volatility of the entrapped ingredients or time. To date, no formulation of sunscreen based on multiparticulate delivery is available in the market. In the light of the research reported so far, multiparticulate delivery systems appear to have potential applications in the formulation development indicating the role 96 International Journal of Cosmetic Science, 32, 89 98

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