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Background: 18β- glycyrrhetinic acid (Gly) is the major bioactive component of licorice roots and rhizomes of the Glycyrrhiza glabra species. It shows many activities such as antiviral, anti-inflammatory, antioxidant, antimicrobial, and antifungal, however, its use in the health field is very limited due to the low water solubility. Methods: This paper deals with the development of a new technological approach for Gly dissolution rate enhancement. It consists of Gly intercalation (guest) in the interlamellar spaces between the inorganic spaces (host) of the anionic clays “hydrotalcites” (HTlc) to obtain hybrids MgAl-HTlc-Gly and ZnAl-HTlc-Gly. Gly can find applications in both systemic and local therapies, thus advantages of the use of the hybrids in these two fields were investigated. Results: Gly dissolution rate from hybrids in the intestinal environment, site in which it is preferentially absorbed, resulted enhanced (ZnAl-HTlc-Gly > MgAl-HTlc-Gly) compared to the crystalline form, thereby, making them suitable for oral administration as dry powder in hard capsules. : For a local therapy, bioadhesive, vaginal emulgels loaded with the hybrids were developed. These showed suitable mucoadhesive property to the vaginal mucosa, necessary to prolong the residence time in the application site. The emulgel containing ZnAl-HTlc-Gly showed a faster and higher release profile than that containing MgAl- HTlc-Gly. Conclusions: The obtained results suggest that Gly intercalation into HTlc, especially in ZnAl-HTlc, allows to enhance Gly dissolution when the hybrids are formulated both as oral or topical products.

The knowledge about the effect of hydrotalcites (HTlcs), largely used in pharmaceutics, on non-malignant cell lines is limited. The effect of MgAl-HTlc-and ZnAl-HTlc- (NO3−/Cl−/CO32−) on the cell viability of HaCat, fibroblasts and HepG2 was studied by MTT assay. Cells were incubated either with HTlc suspensions in the culture media and with the supernatant obtained from the suspension being centrifuged. MgAl-HTlcs suspensions resulted in being cytotoxic. As SEM and TEM analyses showed the presence of sub-micrometric particles in all the MgAl-HTlc examined, it could be hypothesized that this fraction can be internalized into cells reducing the viability. MgAl-HTlc-NO3 is the most cytotoxic probably due to the additional effect of NO3− anions. ZnAl-HTlcs are cytotoxic, especially for HaCat and HepG2 cells (viability

Dry (D.E.) and liquid (L.E.) extracts were prepared from flaxseeds and their application in health field was evaluated. The chemical analysis showed that D.E. is rich in the lignan secoisolariciresinol diglucoside and L.E. in unsaturated triglycerides containing linolenic acid. Mainly, D.E. showed reducing (15.73 μmol Fe2+/g) and radical scavenging capacities (5.25 mg TE/g) and ability to down-regulate the expression of the pro-inflammatory cytokines NO (IC50 = 0.136 ± 0.009 mg/mL) and IL-6 (IC50 = 0.308 ± 0.103 mg/mL), suggesting its use in wound treatment. D.E. and L.E. were active against S. pyogenes and D.E. also against S. aureus. The two extracts were combined in a novel O/W emulgel in which the water phase was viscosized using a low molecular weight and highly deacetylated chitosan (1% wt./v). The presence of this polymer in the emulgel decreased the MIC values of the extracts. In fact, MIC shifted from 0.59 mg/mL to 0.052 mg/mL for D.E. and from 0.22 mg/mL to 0.036 mg/mL for L.E., concentrations safe both for keratinocytes and macrophages. Moreover, the emulgel demonstrated to inhibit S. aureus, P. aeruginosa, S. pyogenes, E. coli, and K. pneumoniae growth (inhibition halos 24–36 mm), strains often responsible for diabetic foot ulcer infection.

Folic acid (FA) is a key factor in the physiological processes of cell metabolism; as it is involved in DNA synthesis and repair, it can be used in the treatment of aged and photo-damaged skin. The main drawbacks associated to FA use, particularly for topical applications, are the limited solubility and the sensitivity to UV rays. Hybrids of FA with two kinds of layered double hydroxides (ZnAl-LDH and MgAl-LDH) were prepared and characterized showing suitable particle size, flow properties and UV photoprotection. The introduction of FA-LDHs in the external water phase of O/W emulgels produced an enhancement of their flow properties; moreover, the spectrophotometric analyses showed that very good photostability is maintained even after their introduction into the formulations. In-vitro release studies showed that the FA-LDH containing emulgels promoted a sustained FA release as expected. Finally, the safety of FA-LDH was evaluated by in-vitro studies performed on human keratinocytes (HaCaT) and human primary dermal fibroblasts (as a skin representative). The obtained results showed a high cytotoxic effect of ZnAl-LDH-FA in both cell lines.

Hazelnut shells represent a waste material (about 42% of the total biomass) deriving from hazelnut harvest. These are mainly used as a heating source, however, they represent an interesting source of polyphenols useful in health field. The impact on phenolic profile and concentrations of hazelnut shell extracts obtained by three extraction methods (maceration, ultrasonic bath, and high-power ultrasonic), as well as temperature, extraction time, and preventive maceration, was studied. The prepared extracts were characterized in terms of chemical composition, antioxidant and antimicrobial activities. Eighteen different phenolic compounds were identified and quantified by chemical analysis and gallic acid was the most abundant in all the extracts analyzed. Other relevant compounds were chlorogenic acid, protocatechuic acid and catechin. Preventive maceration had a positive effect on the extraction of different types of compounds regardless of the method performed. Application of the high-power ultrasonic method had different effects, either positive or negative, depending on the type of compound and extraction time. All the prepared extracts showed antioxidant activity especially those prepared by maceration, and many of them were able to inhibit the growth of both B. subtilis and B. cereus.

Authors sincerely acknowledge Marco Marani from the Department of Pharmaceutical Sciences for technical assistance, and Simonetta De Angelis from ASL N. 1 (Città di Castello, Perugia, Italy) for providing pig skin samples., Pycnogenol (PYC) is a concentrate of phenolic compounds derived from French maritime pine; its biological activity as antioxidant, anti-inflammatory and antibacterial suggests its use in the treatment of open wounds. A bioadhesive film, loaded with PYC, was prepared by casting, starting with a combination of two biopolymer acqueous solutions: xanthan gum (1% wt/wt) and sodium alginate (1.5% wt/wt), in a 2.5/7.5 (wt/wt) ratio. In both solutions, glycerol (10% wt/wt) was added as plasticizing agent. The film resulted in an adhesive capable to absorb a simulated wound fluid (similar to 65% wt/wt within 1 h), therefore suitable for exuding wounds. The mechanical characterization showed that the film is deformable (elastic modulus E = 3.070 +/- 0.044 MPa), suggesting adaptability to any type of surface and resistance to mechanical solicitations. PYC is released within 24 h by a sustained mechanism, achieving a maximum concentration of similar to 0.2 mg/mL, that is safe for keratinocytes, as shown by cytotoxicity studies. A concentration of 0.015 mg/mL is reached in the first 5 min after application, at which point PYC stimulates keratinocyte growth. These preliminary results suggest the use of PYC in formulations designed for topical use.

Cutaneous adverse effects are often associated to cancer therapies. Modifications of the aspect represent one of the factors responsible for quality of life decrese, particularly visible in women. It must be underlined also that in many female tumors the cutaneous adverse effects are often enhanced by the hormonal levels inducing skin damage and photoinduced reactions. In this scenario the cosmetic oncology plays a very important role. In fact, it is a branch of cosmetic, having high social and ethical value born to support oncological patients by physical appearance improvement. The skin and cutaneous annexes of the oncological patient are different in comparison to that of health people requiring particular attention. In first instance a high skin protection and hydration is necessary for such patients. For this reason, the cosmetic oncology supports the oncological patients in the improvement of their appearance by means of specific products and skin care procedures. Projects of cosmetic oncology, involving many territorial pharmacies, raised with the idea that the attenuation of the external signs therapy-induced can contribute to the improvement of the patient quality of life.

Authors sincerely acknowledge Morena Nocchetti for X-ray patterns and registration and Marco Marani for technical assistance from the Department of Pharmaceutical Sciences. Authors wish to thank Simonetta De Angelis from ASL N. 1 (Città di Castello, Perugia, Italy), for providing pig skin samples., Ketoprofen (KET) represents one of the most common drugs used in the topical treatment of pain and inflammations. However, its potential is rather limited due to the very low solubility and photochemical instability. The local administration of KET by conventional products, such as gels, emulgels, creams, and foams, does not guarantee an efficacious and safe treatment because of its low absorption (due to low solubility) and its sensitivity to UV rays. The photodegradation of KET makes many photoproducts responsible for different adverse effects. In the present work, KET was intercalated into the lamellar anionic clay ZnAl-hydrotalcite (ZnAl-HTlc), obtaining the hybrid ZnAl-KET with improved stability to UV rays and water solubility in comparison to the crystalline form (not intercalated KET). The hybrid was then formulated in autoadhesive patches for local pain treatment. The patches were prepared by casting method starting from a hydrogel based on the biocompatible and bioadhesive polymer NaCMC (Sodium carboxymethycellulose) and glycerol as a plasticizing agent. The introduction of ZnAl-KET in the patch composition demonstrated the improvement in the mechanical properties of the formulation. Moreover, a sustained and complete KET release was obtained within 8 h. This allowed reducing the frequency of anti-inflammatory administration, compared to the conventional formulations

The onion non-edible outside layers represent a widely available waste material deriving from its processing and consumption. As onion is a vegetable showing many beneficial properties for human health, a study aiming to evaluate the use of extract deriving from the non-edible outside layers was planned. An eco-friendly extraction method was optimized using a hydroalcoholic solution as solvent. The obtained extract was deeply characterized by in vitro methods and then formulated in autoadhesive, biocompatible and pain-free hydrogel polymeric films. The extract, very soluble in water, showed antioxidant, radical scavenging, antibacterial and anti-inflammatory activities, suggesting a potential dermal application for wounds treatment. In vitro studies showed a sustained release of the extract from the hydrogel polymeric film suitable to reach concentrations necessary for both antibacterial and anti-inflammatory activities. Test performed on human keratinocytes showed that the formulation is safe suggesting that the projected formulation could be a valuable tool for wound treatment.

18β-glycyrrhetinic acid (Gly), a natural compound obtained from licorice, is known both for the anti-inflammatory and antioxidant activities and for this reason useful for wound treatment. Due to its poor solubility, Gly is not suitable for formulations used in conventional topical products such as gels, foams and creams. Polymeric bioadhesive microparticles (MP), loaded with Gly, were developed to be introduced in the wound bed and swell, once in contact with the exudate, to form a hydrogel in situ able to close the wound. The MP were prepared by spray drying method from the polymeric solution of polysaccharide sodium carboxymethyl cellulose (CMC) and copolymer Soluplus® (SL). Soluplus® introduction in MP composition, using a 3:1 ratio (CMC/SL wt./wt.), allowed to stabilize Gly in non-crystalline form, favoring the improvement of water solubility, and to obtain a spherical with rugged surface MP morphology. Ex vivo studies showed these MP maintain high swelling capability and are able to form in situ a hydrogel for wound repair. The controlled release of Gly from the hydrogel stimulates keratinocyte growth, potentially supporting the physiological healing processes.

Introduction The mucositis is an inflammatory, erosive and ulcerative process of the oral mucosa. It is usually caused by radiation, chemotherapy, infections, diabetes, smoking and it is characterized by severe pain and difficulty eating and can have a very serious impact on quality of life. A suitable treatment must ensure pain control and mechanical protection to promote mucosal healing. The purpose of this work was to study an in-situ gelling formulation to be sprayed onto the damaged oral mucosa by self-administration. The formulation must be able to quickly form a film when applied in the oral cavity. Methods many batches were prepared mixing a thermosensitive polymer (poloxamer PF127 or P123) with mucoadhesive polymers polyvinylpyrrolidone (PVP), sodium carboxymethyl cellulose (NaCMC), Carbopol 971P, chitosan (CS). By an experimental design three suitable formulations were identified and loaded with the model drug benzydamine hydrochloride. The hydrogel based on 25.50% PF127, 0.20% PVP and 0.35% CS maintained its original properties (gelling, rheological and mucoadhesive) after loading and showing a sustained drug release. Conclusions the selected hydrogel showed to be suitable for the treatment of mucositis, able to reduce the number of daily administration and to protect the damaged mucosa from mechanical and chemical solicitations.

Taxifolin possesses gastroprotective property but is characterized by low water solubility, is instabile in alkaline medium, and is degraded by the intestinal bacteria flora. The purpose of the work was therefore to produce a gastroadhesive formulation to prolong taxifolin residence time and release in the stomach. We first demonstrated that taxifolin is stable in simulated gastric fluid with or without pepsin and mucus, and is able to cross pig gastric mucus layer and stomach mucosa. Next, gastromucoadhesive microparticles composed of Syloid® AL-1 mesoporous silica, chitosan and HPMC were produced using spray-drying. Microparticles were characterized by a spherical shape and a mean volume-equivalent diameter around 12 μm. The optimized microparticles were able to release taxifolin and to adhere to pig stomach mucosa for 5 h.

Anti-caries activity of fluoride ions is due to the protection against demineralization and the enhancement of remineralization of tooth enamel. Dentifrices available on the market contain sodium fluoride, sodium monofluorophosphate, stannous fluoride, and amine fluoride as source of these ions. A new compound working both as fluoride ion source and as abrasive was projected. Hybrids based on F- ions intercalated between the lamellae of hydrotalcite-like compounds (HTlc-F), namely MgAl-HTlc-F and ZnAl-HTlc-F, were prepared and characterized. Then, three different percentages (2, 3, and 4%) of both HTlc-F compounds were assayed. After the rheological characterization, the dentifrices containing 3 and 4% of MgAl-HTlc-F and ZnAl-HTlc-F, respectively, resulted to be the most suitable ones. Two novel in vitro methods, "rotary toothbrush method" and "manual brushing method," were developed and used in order to study the F- ions release from the prepared dentifrices. The obtained results showed that the dentifrice containing ZnAl-HTlc-F (4%) was the most effective in releasing fluoride ions. The "rotary toothbrush method" resulted to be the most suitable as the simulation of the brushing movements is standardizable and reproducible.

Alpha lipoic acid (ALA) is a well-known anti-aging compound. The activity of this molecule is limited by two important factors: (i) The low stability to oxidation and thermal processes and (ii) the low solubility. Particularly the latter limits ALA formulation in hydrophilic bases. The purpose of this paper is to present a new technological approach to stabilize lipoic acid in topical hydrogels for cosmetic use. With this aim, ALA was intercalated in two different lamellar anionic clays (hydrotalcites), MgAl and ZnAl, obtaining the hybrids MgAl-ALA and ZnAl-ALA. The intercalation allows to obtain a more manageable product in comparison to raw ALA. After the preliminary characterization, hydrogels containing the hybrids were prepared and characterized, also in comparison to the commercial product Tiobec® in terms of rheological properties, stability to temperature and centrifugation, release, and cytotoxicity. The obtained results highlighted that the hydrogel containing MgAl-ALA is a suitable alternative to the products currently available on the market.

Usnic acid (UA) is a lichenic secondary metabolite useful for the treatment of burn wounds thanks to its antimicrobial activity, particularly toward strains responsible for their infections. However, the poor solubility is the main factor limiting the activity and thus its use in health care products. Adhesive polymeric films were designed to improve UA use by enhancing its bioavailability in the wounded tissues. Three different NaCMC hydrogel films, NaCMC 2% alone (F1), mixed to PVP K90 0.1% (F2) or to Carbopol 971 P 0.1% (F3), were prepared by casting method. Ex vivo experiments performed on pig skin samples showed their suitable adhesion capacity. in vitro release test, performed using the extraction cell, showed that film F2 provides the highest UA concentrations. Differential scanning calorimetry and X-ray analyses performed on the three films highlighted that UA is present in a more soluble form in F2. The in vitro antibacterial activity studies demonstrated that F2 is the most effective film against UA sensitive bacteria S. Epidermidis, E. Faecalis, B. Cereus and S. Pyogenes. In vitro cytotoxicity assays on human keratinocytes and fibroblasts showed that cells viability is not compromised.

The aim of this study was to develop an innovative formulation, particularly useful for the treatment of exuding wounds. An extract from Moringa oleifera leaves (MOE), prepared by an eco-friendly method, was used as active ingredient. Its preliminary characterization showed that MOE is rich in quercetin-O-glucoside and quercetin-O-malonyl glucoside, responsible for the antioxidant, radical scavenging and antibacterial activities (toward Staphylococcus aureus, S. epidermidis, S. faecalis and S. pyogenes). Moreover, MOE showed the ability to stimulate keratinocytes growth. Thus, bioadhesive biocompatible polymeric microparticles loaded with such extract were developed and prepared in order to treat exuding wounds. The microparticles, obtained by spray drying, using chitosan as polymer, showed good swelling ability. This is useful to obtain the transition from microparticles to a continuous gel covering the wound, after deposition on it. This has the double function to protect the damage area and to promote the healing. The in vitro release study showed that the formed gel is able to release immediately MOE, in the first minutes after application, and to promote a sustained release within 24 h reaching an efficacious concentration against the most sensitive bacterial strains. These findings suggest that the developed microparticles represent an interesting tool for exuding wounds treatment.

In recent years inorganic materials are largely present in products intended for health care. Literature gives many examples of inorganic materials used in many healthcare products, mainly in pharmaceutical field. : Silver, zinc oxide, titanium oxide, iron oxide, gold, mesoporous silica, hydrotalcite-like compound and nanoclays are the most common inorganic materials used in nanosized form for different applications in the health field. Generally, these materials are employed to realize formulations for systemic use, often with the aim to perform a specific targeting to the pathological site. The nanometric dimensions are often preferred to obtain the cellular internalization when the target is localized in the intracellular space. : Some materials are frequently used in topical formulations as rheological agents, adsorbents, mattifying agents, physical sunscreen (e.g. zinc oxide, titanium dioxide), and others. : Recent studies highlighted that the use of nanosized inorganic materials can represent a risk for health. The very small dimension (nanometric) until a few years ago represented a fundamental requirement; however, it is currently held responsible for the inorganic material toxicity. This aspect is very important to be considered as actually numerous inorganic materials can be found in many products available in the market, often dedicated to infants and children. These materials are used without taking into account their dimensional properties with increased risk for the user/patient. : This review deals with a deep analysis of current researches documenting the toxicity of nanometric inorganic materials especially those largely used in products available in the market.

Layered double hydroxides (LDHs) find many applications in the pharmaceutical field. Often, the synthetic product requires a suitable grinding procedure before starting any type of manufacturing process. Choosing the appropriate grinding procedure is important; it must reduce the particle size without modifying the LDH's native layered structure and crystal morphology. Using the LDH MgAl-NO3 as model sample, the aim of this paper was to investigate the influence of three common grinding procedures: knife mill, ball mill and jet mill, on particles size, morphology, specific surface area, crystallinity and flow character. Results highlighted that the jet milling procedure is the most appropriate method to induce particle size reduction while maintaining the original MgAl-NO3 features.

Therapeutic efficacy of some orally administered molecules is often conditioned by their solubility in physiological fluids as well as their absorption. The last aspect becomes more limitative and conditioning drug plasmatic profiles when the active ingredient is preferentially absorbed in a specific region of the gastrointestinal tract. A case is represented by furosemide (FURO) preferentially absorbed in the stomach, site in which, because of its acidic nature, is poorly soluble. To solve this problem new oral solid formulations have been developed. The inorganic-organic hybrid MgAl-HTlc-FURO has been formulated in tablet in which floating and mucoadhesion properties have been combined. Swellable (Methocel K4, Methocel K15, Methocel K100 M, hydroxypropyl methyl cellulose) or swellable/erodible polymers (Methocel E50 LV, Methocel K100 LV), used to obtain the floating, were combined to Carbopol(®) (971P or 974P) to confer mucoadhesion capacity. Prepared tablets were deeply characterized in terms of hydration capacity, erosion %, buoyancy lag time/floating time and mucoadhesion. The most suitable tablets selected from these preliminary tests, submitted to in vitro release studies, showed a sustained release of FURO. This is useful to maintain the therapeutic concentrations for a long time, in comparison to conventional dosage forms, thanking to the enhancement of formulation residence time in the stomach.

Summary The purpose of this study was to extract functional components, such as phenols, from wine under mild conditions and without the use of organic solvents. A dry and alcohol-free concentrated wine bioactive extract was obtained using layered double hydroxides (LDHs). The influence of some factors (LDH type, temperature, time and LDH/wine ratio) was evaluated using an experimental design software. Three responses were selected (phenol, anthocyanin and catechin contents). Using the optimised results, the best extraction conditions were as follows: pH 3.7, time 240 min, ratio 3, temperature 20 °C. The sample prepared in these conditions was characterised technologically (size, flowability, wettability) to investigate its manageability and workability. The phenol extract obtained using MgAl-LDH had suitable particle size and good flowability. A formulation of concentrated wine phenol extract with interesting applications for the nutraceutical field was successfully produced.

Kojic acid (KOJ) is a melanin synthesis inhibitor widely used as skin lightening agent in topical preparations. Unfortunately it is easily susceptible to photo-oxidation, phenomenon responsible for chemical and organoleptic modifications. The aim of this work was the intercalation of KOJ in hydrotalcite-like compounds (HTlc) in order to stabilize KOJ and to reduce its photolability. Hydrotalcite containing Zn and Al (ZnAl-HTlc) was used as host to obtain the final compound ZnAl-HTlc-KOJ. The intercalation was carried out, after many attempts, by ionic exchange mechanism by means of the strong base EtO

Oral administration of poorly soluble drugs represents a challenge for the pharmaceutical industries. This research proposes the realization of host–guests composites in which the model drug furosemide (FURO), labeled in class IV of BCS, was chosen as guest whereas hydrotalcite like compounds (HTlcs) were used as host materials. Two intercalation products, MgAl-HTlc-FURO and ZnAl-HTlc-FURO, were prepared and characterized. Once intercalated the drug is not organized as crystals but gives rise to a new product in which it is molecularly dispersed forming a molecular film that could be defined “shell-liquid state”, in the nanospaces of the interlayer region. In vitro release studies resulted that both intercalation products are able to promote drug dissolution enhancement, however, because of their different physicochemical properties MgAl-HTlc-FURO gave the best results. Then this product was submitted to supersaturation assay and physical stability studies revealed that drug molecular anions resist the hydrolytic attack and re-crystallization of FURO is prevented during storage conditions.

The use of lysosome-targeted liposomes may significantly improve a delivery of therapeutic enzymes into lysosomes for the treatment of lysosome-associated diseases. The aim of this research was to achieve a specific intracellular targeting of lysosomes, by using liposomes modified with the lysosomotropic octadecyl-rhodamine B (RhB) and loaded with a model compound, fluorescein isothiocyanate (FITC)-dextran (FD). Plain and RhB-modified liposomes were prepared by hydration of lipid films and loaded with FD or with 5-dodecanoylaminofluorescein di-β-d-galactopyranoside (C(12)FDG), a specific substrate for the intralysosomal β-galactosidase. The delivery of these liposomes and their content to lysosomes in HeLa cells was investigated by confocal microscopy, flow cytometry, and subcellular fractionation. Confocal microscopy demonstrated that RhB-liposomes co-localize well with the specific lysosomal markers, unlike plain liposomes. The comparison of the FITC fluorescence of the lysosomes isolated by subcellular fractionation also showed that the efficiency of FD delivery into lysosomes by RhB-modified liposomes was significantly higher compared with plain liposomes. These results were additionally confirmed by the flow cytometry of the intact cells treated with C(12)FDG-loaded liposomes that also demonstrated increased lysosomal targeting by RhB-modified liposomes. The modification of the liposomal surface with a lysosomotropic ligand, such as octadecyl-RhB, can significantly increase the delivery of liposomal loads to lysosomes.

The poor solubility carbamazepine (CARBA) is the main responsible for its low and variable bioavailability. This problem is strictly connected to the high energy required for CARBA crystal lattice disruption that represents the rate determining step of the dissolution process. CARBA dissolution enhancement can be achieved by converting the crystals ordered structure in the amorphous solid state in which the molecules show a high mobility, requiring less energy for intermolecular bond breaking. Unfortunately CARBA amorphous form is unstable and turns into the crystalline one. The aim of this work was the improvement of CARBA dissolution by its conversion in the amorphous form and its stabilization by inclusion in the mesoporous silica material SBA-15. CARBA was loaded by a simple, safe and eco-friendly method obtaining a high final drug loading (40% wt.). The obtained inclusion product showed improved drug dissolution and good physical stability in comparison to crystalline CARBA. Interesting results were obtained also for the physical mixture of SBA-15 and CARBA which showed an increase of drug dissolution. Moisture effects on drug amorphous form stability are discussed as well.

The effect of different preparation parameters were analyzed with respect to the rheological and pharmaceutical characteristics of hydrogel blend patches, as transdermal delivery formulation. Mixtures of pectin and gelatin were employed for the production of patches, with adjustable properties, following a two-step gelation procedure. The first gelation, a thermal one, is trigged by the presence of gelatin, whereas, the second gelation, an ionic one, is due to the formation of the typical egg box structure of pectin. In particular, the patch structural properties were assessed by oscillation stress sweep measurements which provided information concerning their viscolelastic properties. In addition, different modalities for drug loading were analyzed with respect to drug homogeneous distribution; testosterone was employed as model drug for transdermal administration. Finally, the performances of the produced transdermal patches were studied, in term of reproducibility and reliability, by determination of in vitro drug release profiles.

The aim of this work was to develop new mucoadhesive buccal patches containing an inorganic fluorinated compound, MgAl-F, intended for decay prevention. Firstly MgAl-F was synthesized and characterized, then the patches were prepared starting from a physical blend of mucoadhesive polymers (NaCMC and polycarbophil) in which MgAl-F was dispersed in different amounts in order to obtain the films. The prepared mucoadhesive patches were characterized in terms of swelling capacity, mucoadhesion force and time, surface morphology and in vitro release studies. Moreover, the organoleptic properties and acceptability have been evaluated by in vivo application. The performed studies demonstrated that the proposed formulations are practical, manageable, flexible and adaptable to the biological substrate showing, at the same time, good organoleptic properties. Moreover, the presence of the MgAl-F is able to decrease the strong adhesion of the employed polymers, reducing pain and irritations resulting in a high patient acceptability. Data obtained from release studies revealed that the application of small patch portions is enough able to release, for a prolonged time, an amount of fluoride ions able to reach the efficacious dose. These observations suggest the applicability of such formulations for buccal administration of different active ingredients.

The purpose of this research work was the realization of a bi-layered mucoadhesive dosage form intended for carbamazepine sublingual administration and planned in order to obtain a unidirectional drug release and diffusion only across buccal mucosa avoiding the liberation in the buccal environment. Bi-layered tablets were constituted by an impermeable ethyl cellulose backing layer and a mucoadhesive layer. The latter was composed by a blend of a semisynthetic polymer, as hydroxyethyl cellulose or hydroxypropyl methylcellulose, and a synthetic polymer as, Carbopol(®), physically mixed in different ratios. The active ingredient carbamazepine was homogeneously dispersed in the mucoadhesive layer. The prepared formulations were carefully characterized by thickness, friability, swelling index, matrix erosion, ex vivo and in vivo mucoadhesive force and time, moreover patient acceptability was evaluated as well. Tablets constituted by Carbopol(®):hydroxypropyl methylcellulose (25%:75%) and Carbopol(®):hydroxyethyl cellulose (75%:25%) showed the best properties and for this reason were submitted to in vitro release studies. Both tablet groups gave good results in terms of ex vivo and in vivo bioadhesive force and time giving a sustained release.

Octyl methoxycinnamate (OMC) is a widely used UV filter characterized by good absorbing properties; however, it shows light susceptibility (photoinstability) and potential skin permeation. This paper describes the application of a new particulate carrier to improve OMC safety and photostability. The UV filter was included into the pores of the mesoporous silicate MCM-41 and then entrapped there by plugging the pore openings. The last step was performed treating the MCM-41 inclusion product with a lipid cosmetic ingredient by the hot-melt method. The loaded samples were characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, and N 2 adsorption isotherms. Photochemical studies demonstrated that the coated samples allow a broader photoprotection range and remarkable improvement of sunscreen photostability. Finally, they were properly formulated in an emulgel, and the sunscreen release was studied in vitro by Franz diffusion cell and compared with those obtained from the same formulation containing the free filter. Sunscreen release from the studied formulations resulted negligible, meaning that the proposed approach represents a valuable strategy for UV filters stabilization toward light and safety improvement.

Many active pharmaceutical ingredients (APIs), in development and already on the market, show a limited and variable bioavailability mainly associated to inadequate biopharmaceutical properties such as aqueous solubility and dissolution rate. The latter is the main factor responsible for the limited, and sometimes inadequate, efficacy of many orally administered drugs, belonging to class II and IV of the Biopharmaceutics Classification System (BCS). Moreover, because of their low solubility, such drugs require high doses to be administered in order to obtain their pharmacological effect, increasing the side effect incidence.The present review reports the most common technological approaches intended to improve solubility and dissolution rate of BCS class II and IV drugs such as nanocrystals, solid dispersions, cyclodextrins and solid lipid nanoparticles. Particular attention will be focused on the use of inorganic matrices (lamellar anionic clays and mesoporous materials) as host for the delivery of poor soluble APIs (guest).The employment of inorganic matrices for the realization of host-guest composites is a suitable strategy for the biopharmaceutical properties enhancement. This objective can be achieved without any modification of API chemical structure.

Furosemide (FURO) is a BCS class IV drug preferentially absorbed in the gastric environment. A previous study demonstrated that its intercalation into the lamellar inorganic matrix MgAl-HTlc, giving rise to MgAl-HTlc-FURO, improves its dissolution in acidic medium. As the gastric absorption of drugs can be hindered from the biological barriers mucus and gastric mucosa, the purpose of this work was to evaluate the effect of MgAl-HTlc on gastric pH, the possible modifications induced on mucus rheology and the influence on both artificial and biological membranes.Firstly the effect of growing MgAl-HTlc concentrations on gastric pH was evaluated. Both drug flux across the mucus layer and permeability across an artificial and biological membrane (gastric mucosa) have been studied as well.The results highlighted that drug flux across gastric mucus is improved in presence of MgAl-HTlc-FURO and that MgAl-HTlc is able to modify mucus structure in a reversible manner. From permeability studies emerged that the use of a biological membrane is the most suitable for such studies and that MgAl-HTlc-FURO enhances FURO Papp.Data obtained suggest that MgAl-HTlc is a suitable material able to improve the biopharmaceutical properties of class IV BCS drugs.