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In this study several essential oils (EOs): basil - BA, lemon balm - LB and oregano - OR were incorporated into nanoemulsions (NEs) as prospective carriers for natural and sensitive bioactives. NEs were prepared via the phase inversion composition (PIC) method, which is an energy-efficient cold process. Physicochemical stability of NEs was confirmed by particle size distribution analysis, electrical conductivity and pH value measurements, as well as by optical microscopy observations. The type of EO and the surfactant and oil mix concentration were found to be crucial factors governing the NE properties and stability. Raman spectra of the EOs confirmed main active ingredients and provided detection of interactions with the nanocarrier, which is a novel application of this technique. The antioxidant activity towards DPPH radical in methanol was concentration-dependent with a similar trend for individual oils and oil-loaded NEs (OR> LB> BA). However, the ABTS test in an aqueous medium revealed notable change in the order of activity after EO nanonisation at higher EO concentrations. Overall, it was found that OR-NE was the most effective and stable system, since OR acted as a co-stabiliser in the NE formulation, and its remarkably high antioxidant activity was successfully preserved during 6 months of storage. U ovoj studiji nekoliko različitih etarskih ulja (EU): bosiljak – BO, matičnjak – MA i origano – OR inkor- porirano je u nanoemulzije (NE) kao potencijalne nosače za prirodne i osetljive bioaktivne sastojke. NE su pripremljene pomoću metode inverzije faza (engl. phase inversion composition – PIC method) koja predstavlja niskoenergetski i ekonomičan postupak izrade. Fizičkohemijska stabilnost nanoemulzija potvrđena je analizom raspodele veličina kapi, merenjem električne provodljivosti i pH vrednosti, kao i optičkom mikroskopijom. Nađeno je da su vrsta EU i koncentracija smeše surfaktanata i uljane faze dva ključna faktora koja su uticala na karakteristike i stabilnost dobijenih emulzija. Tehnikom Ramanske spektroskopije potvrđeni su glavni aktivni sastojci etarskih ulja i detektovane su moguće interakcije sa nanonosačem, što predstavlja noviju primenu pomenute tehnike. Pokazano je da antioksidantna aktivnost prema DPPH radikalu u metanolu zavisi od koncentracije, sa sličnim trendom za čista etarska ulja i za nanoemulzije sa uljima (OR> MA> BO). Međutim, ABTS test u vodenoj sredini pokazao je izrazite promene u redosledu aktivnosti sa povećanjem koncentracije EU i nakon nanonizacije EU. Generalno, dokazano je da je OR-NE najefikasniji i najstabiliniji sistem, s obzirom da je ulje origana ispoljilo ulogu kostabilizatora u formulaciji, uz istovremeno očuvanje njegove veoma visoke antioksidantne aktivnosti u obliku nanoemulzije, tokom 6 meseci čuvanja.

Objective: The main objective of this work was to evaluate the performance of recently developed dynamic-mechanical thermoanalysis (DMTA) test as a rapid rheological alternative to conventi...

The acidic skin pH is one of the regulating factors of skin barrier homeostasis. Topical products as extrinsic factors which influence skin pH could be used for acidification of the skin and consequent beneficial effect. To formulate stabile and safe topical emulsion product with low pH is on-going challenge and areas interesting to explore are related to the effect of acidic products on the skin pH together with development of protocols for these studies. Aim of our work was to investigate formulations of acidic topical products with glycolic acid (GA) stabilized with long chain alkyl polyglucoside emulsifier, in regard to the specific colloidal structure of the vehicle, together with effect of products with different concentration of acidic active on skin pH.Investigated formulations were basic vehicle and two creams with glycolic acid (concentration 2 and 10 wt%). Microstructure was investigated by polarization microscopy, Raman spectral imaging, thermal analysis and rheological measurements. Effects on the skin were assessed by measurement of biophysical skin parameters in vivo studies (5-hour, 24-hour and 7-days). In vitro screening of antimicrobial activity was performed against bacteria Staphylococcus epidermidis.Polarization micrographs and Raman images have shown that GA does not disturb the specific colloidal structure. Together with rheological and thermal analysis obtained results have shown that GA in higher concentrations contributes to vehicles' lamellar structure. In 5-hour study the mean values of skin pH ranged from 3.98-4.25 and 3.89-4.10 after application of products with smaller and higher GA concentration. GA samples lowered skin surface pH to 5 and less in 24-hour and 7-day study, with stronger effect of sample with more GA. Sample with 10% of GA had significant inhibitory effect on growth of S. epidermidis in 1:1 concentration.Investigated APG emulsifier could be used as a stabilizer for acidic topical products with GA which are characterized by satisfactory safety profile. Topical products induce acidification of the skin after short- and long-term application without barrier impairment or sign of irritation. Acidification of the skin depends on presence of ingredients which are proton donors and their concentrations.Le pH acide de la peau est l’un des facteurs de régulation de l’homéostasie de la barrière cutanée. Les produits topiques pourraient être utilisés en tant que facteurs extrinsèques d’influence du pH cutané pour permettre l’acidification de la peau et obtenir l’effet bénéfique qui en résulte. Formuler des émulsions topiques stables et sûres à faible pH représente un défi constant et les domaines d’étude dignes d’intérêt portent sur l’effet des produits acides sur le pH cutané et sur l’élaboration de protocoles pour ces études. L’objectif de notre travail était d’étudier des formulations de produits topiques acides à base d’acide glycolique (AG) stabilisé à l’aide d’un émulsionnant à base d’alkylpolyglucoside (APG) à longue chaîne, par rapport à la structure colloïdale spécifique de l’excipient, ainsi que l’effet des produits à différentes concentrations d’acide actif sur le pH cutané. MÉTHODES: Les formulations étudiées étaient un excipient de base et deux crèmes à base d’acide glycolique (concentration égale à 2 % et 10 % de la fraction massique). La microstructure a été étudiée par microscopie à polarisation, par spectroscopie Raman, par analyse thermique et par mesures rhéologiques. Les effets cutanés ont été évalués par la mesure des paramètres cutanés biophysiques dans des études in vivo (5 heures, 24 heures et 7 jours). Un dépistage in vitro de l’activité antimicrobienne a été effectué sur la bactérie Staphylococcus epidermidis. RÉSULTATS: Les micrographies après polarisation et les images obtenues par spectroscopie Raman ont montré que l’AG ne perturbe pas la structure colloïdale spécifique. Avec les analyses rhéologique et thermique, les résultats obtenus ont montré que l’AG à des concentrations plus élevées joue un rôle dans la structure lamellaire des excipients. Dans l’étude de 5 heures, les valeurs moyennes du pH cutané allaient de 3,98 à 4,25 et de 3,89 à 4,10 après l’application des produits présentant une concentration d’AG plus faible et plus élevée. Grâce aux échantillons d’AG, le pH de la surface cutanée a diminué, passant ainsi à une valeur de 5 et à des valeurs inférieures dans les études de 24 heures et de 7 jours, et l’échantillon contenant davantage d’AG a eu un effet plus important. L’échantillon contenant 10 % d’AG a eu un effet inhibiteur significatif sur la croissance de la bactérie S. epidermidis à une concentration de 1:1.L’émulsionnant à base d’APG étudié pourrait être utilisé comme stabilisateur pour les produits topiques acides à base d’AG caractérisés par un profil d’innocuité satisfaisant. Les produits topiques induisent une acidification de la peau après une application à court et à long terme sans altération de la barrière cutanée ou signe d’irritation. L’acidification de la peau dépend de la présence de donneurs de proton parmi les composants et de leurs concentrations.

This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil&mdash, RO and hydro-glycolic fruit extracts from red raspberry&mdash, RE and French oak&mdash, FE. Nanoemulsions were obtained via phase inversion composition (PIC) method at room temperature by dilution of microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic, rheological and Differential Scanning Calorimetry (DSC) investigations. The results have shown that the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet size (Z-ave: 50 to 70 nm, PDI value &le, 0.1). The highest antioxidant activity (~92% inhibition of the DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles and significant improvement in skin hydration during 2 h after application for all nanoemulsions. Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin protection and hydration.

Considering a growing demand for medicinal/cosmetic products with natural actives, this study focuses on the low-energy nanoemulsions (LE-NEs) prepared via the Phase inversion composition (PIC) method at room temperature as potential carriers for natural oil. Four different red raspberry seed oils (ROs) were tested, as follows: cold-pressed vs. CO2- extracted, organic vs. non-organic, refined vs. unrefined. The oil phase was optimized with Tocopheryl acetate and Isostearyl isostearate, while water phase was adjusted with either glycerol or an antioxidant hydro-glycolic extract. This study has used a combined approach to formulation development, employing both conventional methods (pseudo-ternary phase diagram - PTPD, electrical conductivity, particle size measurements, microscopical analysis, and rheological measurements) and the methods novel to this area, such as textural analysis and Raman spectroscopy. Raman spectroscopy has detected fine differences in chemical composition among ROs, and it detected the interactions within nanoemulsions. It was shown that the cold-pressed, unrefined, organic grade oil (RO2) with 6.62% saturated fatty acids and 92.25% unsaturated fatty acids, was optimal for the LE-NEs. Textural analysis confirmed the existence of cubic gel-like phase as a crucial step in the formation of stable RO2-loaded LE-NEs, with droplets in the narrow nano-range (125 to 135 nm; PDI ≤ 0.1). The DPPH test in methanol and ABTS in aqueous medium have revealed a synergistic free radical scavenging effect between lipophilic and hydrophilic antioxidants in LE-NEs. The nanoemulsion carrier has improved the biological effect of raw materials on HeLa cervical adenocarcinoma cells, while exhibiting good safety profile, as confirmed on MRC-5 normal human lung fibroblasts. Overall, this study has shown that low-energy nanoemulsions present very promising carriers for topical delivery of natural bioactives. Raman spectroscopy and textural analysis have proven to be a useful addition to the arsenal of methods used in the formulation and characterization of nanoemulsion systems.

Emollients are acknowledged as a part of standard care in therapeutic and prevention protocols as well as a part of everyday skin care routine. When it comes to making a final decision between two emollient products, the ingredient list, that is, the formulation composition could be the determining factor. In such cases the consumer, and some healthcare providers, believe that products with the same qualitative composition (ingredient list) must have the same efficacy. In this study, we have investigated the skin hydration performance of two emollient preparations (DBG and MBG), which appear to contain the same ingredients, and hence, could be considered interchangeable in everyday practice. Our studies showed that the effects of DBG were overall superior to the ones attributed to MBG at each investigated time point (1, 2, 4, and 24 h post application) when tested on normal and dry skin. Consequently, it is shown that two apparently qualitatively identical products do not necessarily provide matching efficacy.

The objective of this work was to develop low-energy nanoemulsions for enhanced dermal delivery of curcumin, using monoterpene compounds eucalyptol (EUC) and pinene (PIN) as chemical penetration enhancers. Spontaneous emulsification was the preparation method. All formulations contained 10% of the oil phase (medium-chain triglycerides (MCT), or their mixture with EUC or PIN). Formulations were stabilized by the combination of polysorbate 80 and soybean lecithin (surfactant-to-oil-ratio=1). Concentration of curcumin was set to 3 mg/ml. Average droplet diameter of all tested formulations ranged from 102 nm to 132 nm, but the ones containing monoterpenes had significantly smaller size compared to the MCT formulation. Such finding was profoundly studied through electron paramagnetic resonance spectroscopy, which proved that the presence of monoterpenes modified the nanoemulsions’ interfacial environment, resulting in droplet size reduction. The release study of curcumin (using Franz cells) demonstrated that the cumulative amount released after 6 h of the experiment was 10.1 ± 0.2% for the MCT nanoemulsions, 13.9 ± 0.1% and 14.0 ± 0.2% for PIN and EUC formulations, respectively. In vivo tape stripping revealed their performances in delivering curcumin into the skin, indicating the following order: EUC>MCT>PIN. The formulation with EUC was clearly the most successful, giving the highest cumulative amount of curcumin that penetrated per surface unit: 34.24±5.68 µg/cm2. The MCT formulation followed (30.62±2.61 µg/cm2) and, finally, the one with PIN (21.61±0.11 µg/cm2). These results corelated with curcumin's solubility in the chosen oils: 4.18±0.02 mg/ml for EUC, 1.67±0.04 mg/ml for MCT and 0.21±0.01 mg/ml for PIN. Probably, higher solubility in the oil phase of the nanoemulsion promoted curcumin's solubility in the superficial skin layers, providing enhanced penetration. This is the peer-reviewed version of the article: European Journal of Pharmaceutical Sciences, 2020, 142, 105135, [https://doi.org/10.1016/j.ejps.2019.105135] The published version: [http://cer.ihtm.bg.ac.rs/handle/123456789/3309]

Objective: The aim of this study was to develop a new dynamic-mechanical thermoanalysis (DMTA) test and evaluate its performance as rapid rheological alternative to routinely used freeze-th...

The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI LT 0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/ mL) and FRAP (1.19 +/- 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities. This is the peer-reviewed version of the article: I. Nikolic, D. Jasmin Lunter, D. Randjelovic, et. al., Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: physicochemical and in vitro peculiarities important for dermal application, International, Journal of Pharmaceutics, 2018, 550, 1-2, 333-346, DOI: [https://doi.org/10.1016/j.ijpharm.2018.08.060] The published version: [https://cer.ihtm.bg.ac.rs/handle/123456789/2425]

Development and validation of a liquid chromatography - tandem mass spectrometry (LC-MS/MS) method for the determination of adapalene in pharmaceutical forms for skin application were presented. The MS/MS analysis of adapalene was performed by use of three mobile phases, consisted of acetonitrile and (a) 0.1 % formic acid, (b) 0.1 % trifluoroacetic acid and (c) 20 mM ammonium acetate. The strongest signals of parent ion and dominant product ion were obtained in negative mode by use of the mobile phase (c). Validation of this method was performed according to the ICH guidelines. Small variations of selected chromatographic parameters (concentration of ammonium acetate, mobile phase composition, column temperature and flow rate) did not affect qualitative and quantitative system responses significantly, which proved method’s robustness. The method is specific for the determination of adapalene. Linearity was proved in the concentration range 6.7 - 700.0 ng mL-1 (r = 0.9990), with limits of detection and quantification 2.0 ng mL-1 and 6.7 ng mL-1, respectively. Accuracy was confirmed by calculated recoveries (98.4 % - 101.5 %). Precision was tested at three levels: injection repeatability, analysis repeatability and intermediate precision. Calculated relative standard deviations were less than 1, 2 and 3 %, respectively. [Projekat Ministartsva nauke Republike Srbije, br. OI172041 i br. TR34031]

The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics. This is the peer-reviewed version of the article: Pajic, N. B., Nikolić, I., Mitsou, E., Papadimitriou, V., Xenakis, A., Randjelović, D., Dobricic, V., Smitran, A., Cekic, N., Calija, B.,& Savić, S. D. (2018). Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. Journal of Molecular LiquidsElsevier Science Bv, Amsterdam., 272, 746-758. [https://doi.org/10.1016/j.molliq.2018.10.002] The published version: [https://cer.ihtm.bg.ac.rs/handle/123456789/2360]

Lichens represent a promising source of antimicrobial, cytotoxic and antioxidant agents. Their great pharmacological potential lies in the fact that they represent specific symbiotic organisms and thus possess natural roles allowing them to be highly adaptable to different environmental conditions. On the other hand, stated biological activities of lichens with prospective medicinal significance may be connected to their long-term use in traditional treatment of various ailments. Genus Usnea from the Parmeliaceae family is certainly one of the best studied in terms of chemical composition and biological properties of its extracts and/or isolated compounds. In the first part of the study, a detailed review of literature has been performed yielding a detailed report on the investigations of biological activities of the lichens belonging to this genus. In the second part of the study, chemical composition of the lichens from the genus was described and, additionally, a survey of the biological properties of the most representative secondary metabolites in these lichens has been reported. It could be concluded that the extracts and/or isolated compounds from the lichens belonging to the genus Usnea may be considered a valuable source of prospective drug candidates with potential clinical relevance.

Context: Approaching of pharmaceutical and cosmetic industries in some aspects inevitably influence formulation of topical pharmaceuticals, urging researchers to introduce novel excipients with proven benefits over traditional ones. In that context, alkyl polyglucosides (APG) emerge as prominent natural-origin emulsifiers with numerous favorable features (biodegradability, dermatological acceptability, desirable sensory properties). Objective: To evaluate APG-stabilized bases (alone and upon addition of isopropyl alcohol) and their impact on skin performance. A simultaneous in vitro/in vivo skin absorption study was conducted to evaluate whether the tape stripping technique could be recommended as an in vivo tool for skin penetration assessment during formulation optimization process. Materials and methods: After a comprehensive physicochemical characterization, biopharmaceutical properties of APG-bases versus reference ones were assessed through a combined in vitro (release/permeation) and in vivo approach. Results and discussion: Physicochemical characterization revealed substantial difference in structural ordering due to the formation of various mesomorphic phases. The enhancer-loaded APG base resulted in significantly higher drug levels at all depths into the stratum corneum, indicating that the selected enhancer along with specific colloidal structure has increased the extent of drug delivery. Conclusion: Results recommend the investigated emulsifier for stabilization of topical drug delivery systems, not only for their ability to sustain the addition of isopropyl alcohol which proved to be a valuable enhancer, but also satisfactory skin absorption and tolerability when compared to samples stabilized by conventional emulsifier. Tape stripping proved to be a useful and yet inexpensive tool for in vivo trials, able to discriminate subtle differences in dermal availability.

Alkyl polyglucosides (APGs) are a perfect amphiphilic structure, with excellent surface activity and solubility feature. The aim of this study is to develop a simple system, with a relatively low emulsifier content, composed of materials mainly naturally based and with no additional fatty alcohol. Hydroxystearyl alcohol and Hydroxystearyl glucoside, prepared with Jojoba and Hazelnut oil, medium chain triglycerides with or without Xylitylglucoside and Anhydroxylitol and Xylitol, have been investigated by using microscopy, rheology, thermal analysis, pH and conductimetry. Cyclic stress and in vivo skin irritation tests were also conducted. The investigated natural APG emulsifier has a capacity to form simple and stable emulsions of desirable rheological profile with improved hydration potential and to renew damaged skin, thus it can be safely applied as stabilizer in cosmetic and prospective pharmaceutical cream-bases.

The aim of the present study was to prepare oil-in-water nanoemulsions stabilized with a novel natural alkyl polyglucoside surfactant and to compare them with corresponding lecithin/polysorbate 80 - based nanoemulsions in terms of physicochemical properties and physical stability. Nanoemulsions were prepared by high pressure homogenization, using 20, 30 and 40% (w/w) medium chain triglyceride as oil phase, and 4, 6 and 8% (w/w) lecithin/polysorbate 80 mixture (1/1) or caprylyl/capryl glucoside as emulsifiers. The influence of emulsifier type, emulsifier concentration and oil content was investigated with respect to changes in particle size, particle size distribution, surface charge and physical stability. The influence of production parameters (number of homogenization cycles, type of homogenization process, homogenization pressure) on particle size was also investigated. Analysis was performed by photon correlation spectroscopy, laser diffraction, zeta potential, pH and electrical conductivity measurements. All formulations produced revealed a small droplet size ranging from 147 to 228 nm and a very narrow size distribution (polydispersity index range 0,072-0,124). Zeta potentials were about -20 mV and -50 mV for nanoemulsions stabilized with lecithin/polysorbate 80 and caprylyl/capryl glucoside, respectively. The results obtained during the stability studies (6 months at 25°C and 1 month at 40°C) indicated that nanoemulsion stability was influenced by their composition. Acquired results also suggested the most appropriate production parameters: 9 homogenization cycles, homogenization pressure of 500 bar and discontinuous process of homogenization.

Recent development of a wide range of regulatory standards applicable to production and use of tissues, cells, and other biologics (or biologicals), as advanced therapies, indicates considerable interest in the regulation of these products. The objective of this study was to analyze and compare high-tier documents within the Australian, European, and U.S. biologic drug regulatory environments using qualitative methodology. Cohort 1 of the selected 18 high-tier regulatory documents from the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and the Therapeutic Goods Administration (TGA) regulatory frameworks were subject to a manual documentary analysis. These documents were consistent with the legal requirements for manufacturing and use of biologic drugs in humans and fall into six different categories. Manual analysis included a terminology search. The occurrence, frequency, and interchangeable use of different terms and phrases were recorded in the manual documentary analysis. Despite obvious differences, manual documentary analysis revealed certain consistency in use of terminology across analyzed frameworks. Phrase search frequencies have shown less uniformity than the search of terms. Overall, the EMA framework's documents referred to “medicinal products” and “marketing authorization(s),” the FDA documents discussed “drug(s)” or “biologic(s),” and the TGA documents referred to “biological(s).” Although high-tier documents often use different terminology they share concepts and themes. Documents originating from the same source have more conjunction in their terminology although they belong to different frameworks (i.e., Good Clinical Practice requirements based on the Declaration of Helsinki, 1964). Automated (software-based) documentary analysis should be obtained for the conceptual and relational analysis.

In this work, we have modified oil phase composition in one component (mineral oil, isocetyl palmitate, special Olive butter and dimethicone 200/350) and the aim of our work was to establish the influence of that alteration on emulsion rheological and textural properties. Additionally, continuous and oscillatory rheological measurements along with texture analysis were assessed in order to predict emulsion application behavior. Based on the obtained results, the change of oil phase has induced a change in the observed rheological and textural parameters and investigated samples can be divided into two distinct groups: the first group – samples with special Olive butter and dimethicone 200/350 and the second group – samples with isocetyl palmitate and mineral oil. Results confirmed that instrumental measurements, as sensitive tools, can be used in order to differentiate emulsions regarding textural properties and especially regarding their actual usage and sensory properties. Practical Applications It is a known fact that the structure of semisolid systems can be characterized by various rheological and textural parameters that are also apt to define certain sensory attributes. Sensory attributes dependent on structure characteristics and flow properties, used for the description of the product in pickup and rub-out phase, could be predicted by instrumental, i.e., rheological and textural measurements. Expensive and time-consuming studies performed with human panelists could be, at least to some extent, replaced with simple rheological and textural measurements. These findings could also contribute to the faster and easier introduction of new raw materials, regarding their characterization and prediction of their influence on the final product characteristics. A combined approach like this could be helpful as both time and money-saving tool for full characterization of a novel consumer-acceptable emulsion product.

To be considered as a suitable vehicle for drugs/cosmetic actives, an emulsion system should have a number of desirable properties mainly dependent on surfactant used for its stabilization. In the current study, C(12-14) alkyl polyglucoside (APG)-mixed emulsifier of natural origin has been investigated in a series of binary (emulsifier concentration 10-25% (w/w)) and ternary systems with fixed emulsifier content (15% (w/w)) with or without glycerol. To elucidate the systems' colloidal structure the following physicochemical techniques were employed: polarization and transmission electron microscopy, X-ray diffraction (WAXD and SAXD), thermal analysis (DSC and TGA), complex rheological, pH, and conductivity measurements. Additionally, the emulsion vehicles' skin hydration potential was tested in vivo, on human skin under occlusion. In a series of binary systems with fixed emulsifier/water ratios ranging from 10/90 to 25/75 the predominance of a lamellar mesophase was found, changing its character from a liquid crystalline to a gel crystalline type. The same was observed in gel emulsions containing equal amounts of emulsifier and oil (15% (w/w)), but varying in glycerol content (0-25%). Different emulsion samples exhibited different water distribution modes in the structure, reflecting their rheological behavior and also their skin hydration capacity.

The two polyhydroxy surfactants polyglycerol 6-distearate (Plurol (R) Stearique WL1009 - (PS)) and caprylyl/capryl glucoside (Plantacare (R) 810 - (PL)) are a class of PEG-free stabilizers, made from renewable resources. They were investigated for stabilization of aqueous solid lipid nanoparticle (SIN) and nanostructured lipid carrier (NLC) dispersions. Production was performed by high pressure homogenization, analysis by photon correlation spectroscopy (PCS), laser diffraction (LD), zeta potential measurements and differential scanning calorimetry (DSC). Particles were made from Cutina CP as solid lipid only (SIN) and its blends with Miglyol 812 (NLC, the blends containing increasing amounts of oil from 20% to 60%). The obtained particle sizes were identical for both surfactants, about 200 nm with polydispersity indices below 0.20 (PCS), and unimodal size distribution (ID). All dispersions with both surfactants were physically stable for 3 months at room temperature, but Plantacare (PL) showing a superior stability. The melting behaviour and crystallinity of bulk lipids/lipid blends were compared to the nanoparticles. Both were lower for the nanoparticles. The crystallinity of dispersions stabilized with PS was higher, the zeta potential decreased with storage time associated with this higher crystallinity, and leading to a few, but negligible larger particles. The lower crystallinity particles stabilized with PL remained unchanged in zeta potential (about -50 mV) and in size. These data show that surfactants have a distinct influence on the particle matrix struture (and related stability and drug loading), to which too little attention was given by now. Despite being from the same surfactant class, the differences on the structure are pronounced. They are attributed to the hydrophobic-lipophilic tail structure with one-point anchoring in the interface (PL), and the loop conformation of PS with two hydrophobic anchor points, i.e. their molecular structure and its interaction with the matrix surface and matrix bulk. Analysis of the effects of the surfactants on the particle matrix structure could potentially be used to further optimization of stability, drug loading and may be drug release.

Background/aims Lactobionic acid (LA) is a newer cosmeceutical active belonging to the class of alpha-hydroxyacids (AHAs), showing advantages over them. The aim of part I of this study was to compare efficacy and irritation potential of LA vs. glycolic acid (GA) from two types of vehicles – gel and emulsion. In part II, effects of LA-containing emulsions based on a new, natural emulsifier of alkylpolyglucoside (APG) type were evaluated. Methods Skin bioengineering was used on 77 healthy volunteers to assess: color as erythema and melanin (MI) index, transepidermal water loss, electrical capacitance and pH of the skin. In part I of the study, the parameters were measured after occlusion and periodically during 2 weeks of test samples application; in part II parameters were measured periodically during 4 weeks. Results/conclusion LA-containing samples has produced better skin performance when compared with corresponding GA-containing ones, particularly the lack of both skin irritation and skin barrier impairment. When used in vehicles based on a new APG-emulsifier, LA and GA have shown better efficacy, emphasizing the importance of vehicle on the effects of topical actives. LA (6%) in the emulsion based on APGs could be proposed as an alternative to low-molecular AHAs in cosmeceuticals.

There is a growing need for in-depth research into new skill- and environment-friendly surfactants, such as alkylpolyglucosides. The aim of this study was to assess whether, to which extent and by what mechanism the two commonly used hydrophilic excipients, propylene glycol (PG) and glycerol (GL), affect the Colloidal structure of emulsions formed by a natural mixed emulsifier, cetearyl glucoside and cetearyl alcohol. Furthermore, the study was concerned with the effect of these changes on in vitro permeation profiles of two model drugs (diclofenac sodium and caffeine) and in vivo skin performance of the test samples. The results have shown that the emulsion vehicles consisted of a complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type. PG addition produced a stronger hydrophilic lamellar gel phase than GL, which was independent on the model drug used. PG-containing vehicles have revealed a considerable amount of interlamellar PG/water mixture, with incorporated drug. In vitro permeation data obtained using artificial skill constructs (ASC) confirmed the relationship between rheological profiles of vehicles and the extent of skill delivery. Higher permeation profiles of both drugs from PG-containing formulations coincided with a higher increase in transepidermal water loss observed in in vivo study on human volunteers, which confirms the penetration/permeation enhancer effect of PG. It also indicates the existence of the vehicle/ASC interactions analogous to those between the vehicle and the skin, thus affirming the use of ASC as a reliable tool for permeation studies. Contrary to the effect of PG, the results obtained with GL suggest that it may have a permeation-retarding rather than a permeation-enhancing effect ill topical vehicles of this type.

There is a growing need for research into new skin- and environment-friendly surfactants. The aim of the study was to find out whether a combination of an alkylpolyglucoside natural surfactant with established pharmaceutical excipients could provide a solid pharmaceutical base with satisfied physical stability. The study was carried out in two phases: the first one focused on the colloidal structure of vehicles formulated with oils of different polarity and/or different costabilizer (lipophilic versus hydrophilic) and the second one evaluated vehicles' physical stability. A number of techniques were used (polarization, light, and transmission electron microscopy, pH, conductivity and thermogravimetric measurements, rheological analysis and cyclic temperature stress test). Natural surfactant's interaction with used excipients resulted in the formation of semisolid emulsion systems of different rheological profiles, stabilized predominantly by synergistic effects of lamellar liquid-crystalline (L alpha) and complex lamellar gel (L beta) phases. The type of used oil and costabilizer significantly influenced the colloidal structure of the vehicles, particularly in terms of water distribution mode and initial rheological performance as well as their physical stability. It was recommended that medium polar oils of ester type and lipophilic costabilizers, particularly long chain fatty alcohols, should be used in the formulation of stable alkylpolyglucoside-based topical vehicles.

There is a worldwide ongoing investigation for novel natural constituents with cytotoxic and antioxidant properties. The aim of this study was to investigate chemical profile and stated biological activities of the supercritical CO2 extract (SCE) of old man's beard compared to the extracts obtained using the conventional techniques (Soxhlet extracts and macerate). The most abundant compound identified was usnic acid, which content was inversely proportional to the polarity of the solvent used and was the highest in the SCE, which was the sample revealing the highest cytotoxic activity in tested tumor cell lines (B16 mouse melanoma and C6 rat glioma), with lower IC50 values compared to pure usnic acid. Further investigations suggested both SCE and usnic acid to induce apoptosis and/ or autophagy in B16 and C6, indicating higher cytotoxicity of SCE to be related to the higher degree of ROS production. A good correlation of usnic acid content in the extracts and their antioxidant capacity was established, extricating SCE as the most active one. Presented results support further investigations of SCE of old man's beard as a prospective therapeutic agent with potential relevance in the treatment of cancer and/ or in oxidative stress-mediated conditions.

Topical treatment of skin infections is often limited by drawbacks related to both antimicrobial agents and their vehicles. In addition, considering the growing promotion of natural therapeutic products, our objective was to develop and evaluate naturally-based emulsion system, as prospective topical formulation for skin infections-treatment. Therefore, alkyl polyglucoside surfactants were used for stabilization of a vehicle serving as potential carrier for supercritical CO2-extract of Usnea barbata, lichen with well-documented antimicrobial activity, incorporated using two protocols and three concentrations. Comprehensive physicochemical characterization suggested possible involvement of extract's particles in stabilization of the investigated system. Raman spectral imaging served as the key method in disclosing extract's particles potential to participate in the microstructure of the tested emulsion system via three mechanisms: (1) particle-particle aggregation, (2) adsorption at the oil-water interface and (3) hydrophobic particle-surfactant interactions. Stated extract-vehicle interaction proved to be correlated to the preparation procedure and extract concentration on one hand and to affect the physicochemical and biopharmaceutical features of investigated system, on the other hand. Thereafter, formulation with the best preliminary stability and liberation profile was selected for further efficiency and in vivo skin irritation potential evaluation, implying pertinent in vitro antimicrobial activity against G+ bacteria and overall satisfying preliminary safety profile.

The aim of the present study was to develop parenteral nanoemulsions containing increasing content of oil phase (20, 30 and 40%, w/w of medium-chain triglycerides-soybean oil mixture at 4:1 ratio), stabilized by lecithin-polysorbate 80 mixture, and to assess their feasibility as carriers for poorly water-soluble psychopharmacological drugs. To this purpose, nanoemulsions loaded with diazepam as a model drug were prepared through high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, viscosity, pH value, and electrical conductivity. Furthermore, the in vitro release of diazepam from developed nanoemulsions was examined using reverse dialysis bag technique, and drug release kinetics was evaluated through several mathematical models. After preparation, all formulations revealed small mean droplet size (206 ± 7 nm), with narrow size distribution (0.116 ± 0.012) and zeta potential around -50 mV, complying with pharmacopoeial requirements (USP 39-NF 34), wherein there were no significant changes in monitored parameters after one year of storage at 25 ± 2°C. In vitro drug release study demonstrated that 40-50% of diazepam was released from actual nanoemulsions within 1 h, while the kinetic release process could be described by Korsmeyer-Peppas model. The results obtained suggest that formulated parenteral nanoemulsions might be promising carriers for rapid delivery of lipophilic, poorly water-soluble psychopharmacological drugs. Cilj ovog istraživanja bio je da se razviju parenteralne nanoemulzije sa rastućom koncentracijom uljane faze (20, 30 i 40% smeše triglicerida srednje dužine lanca i sojinog ulja u odnosu 4:1), stabilizovane kombinacijom lecitina i polisorbata 80, i da se proceni njihova pogodnost kao nosača za slabo rastvorljive psihofarmakološke lekovite supstance. U tu svrhu, homogenizacijom pod visokim pritiskom izrađene su nanoemulzije sa diazepamom kao model lekovitom supstancom i okarakterisane u pogledu veličine kapi, indeksa polidisperznosti, površinskog naelektrisanja, viskoziteta, pH vrednosti i električne provodljivosti. Takođe, primenom reverzne tehnike sa dijaliznim vrećicama procenjena je brzina oslobađanja diazepama iz razvijenih nanoemulzija, uz karakterizaciju dobijenih profila oslobađanja primenom različitih matematičkih modela. Nakon izrade, sve formulacije imale su malu prosečnu veličinu kapi (206 ± 7 nm), sa uskom raspodelom veličina (0,116 ± 0,012) i zeta potencijalom oko -50 mV, što je u skladu sa farmakopejskim zahtevima (USP 39-NF 34) pri čemu se vrednosti navedenih parametara nisu značajno promenile nakon godinu dana čuvanja na 25 ± 2°C. In vitro ispitivanje brzine oslobađanja pokazalo je da se 40-50% diazepama oslobodi iz ispitivanih nanoemulzija tokom 1 h, pri čemu se kinetika oslobađanja može opisati Korsmeyer-Peppas modelom. Dobijeni rezultati ukazuju da formulisane parenteralne nanoemulzije predstavljaju obećavajuće nosače za brzu isporuku slabo rastvorljivih psihofarmakoloških lekovitih supstanci.

There is a growing need for research into new skin- and environment-friendly surfactants. This paper focuses on a natural surfactant of an alkylpolyglucoside type, which can form both thermotropic and lyotropic liquid-crystalline phases. The aim of this study was to relate some physicochemical properties (characterised by polarisation and transmission electron microscopy, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, to the results of in vitro and in vivo bioavailability of hydrocortisone (HC). The three formulations contained oils of different polarity (medium chain triglycerides: MG, isopropyl myristate: IPM and light liquid paraffin: LP), respectively. In vitro permeation was followed through the artificial skin constructs (ASC), while the parameters measured in vivo were erythema index: EI (using instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration (SCH). The vehicles based on cetearyl glucoside and cetearyl alcohol showed a complex colloidal structure of lamellar liquid-crystalline and lamellar gel-crystalline type, depending on oil polarity. Rheological profile of the vehicle was directly related to the in vitro profile of the HC permeation. In vivo results suggested that the vehicle with MG retarded the HC permeation, whereas less polar IPM and non-polar LP enhanced it. It is suggested that the enhancement is achieved either by a direct interaction with lipid lamellae of the SC or indirectly by improving skin hydration. There were no adverse effects during in vivo study, which indicates a good safety profile of this alkylpolyglucoside surfactant.

We aimed to prepare and investigate microparticles with the varying contents of calcium gelling ion, loaded with phenytoin, a standard antiepileptic agent, in its acidic form. Two different methods of alginate-based microparticles preparation were used: with and without treatment with chitosan. Furthermore, two standard procedures, the one-stage and the two-stage, were applied. Microparticle size of 12 one-stage formulations ranged from 466 to 636 mum. Both types of formulations, chitosan-treated and nontreated, appeared to be highly loaded with the model drug (91-96%). The chitosan-coated alginate-based microparticles prepared by the one-stage procedure exhibited kinetics of phenytoin liberation comparable to a similar sustained release system that had been tested at pH 6.8, as published earlier. As the gel erosion of alginate-based microparticles should be potentiated by the higher pH (used in the present study at pH 7.4), the most favorable of 12 formulations, with the liberation half-time of about 2 hr, seemed to be eligible for further modifications. Counterintuitively, the applied two-stage procedure did not appear to beneficially affect the dissolution behavior of phenytoin when tested in two formulations, which makes further modifications necessary.

The present research took an experimental approach to examining strategies of resistance to persuasion. We tested the effects of two strategies (counterarguing and source derogation) and their relation to channel through which a message is received (print, audio and video). The experiment is based on modified experimental paradigm used in one previous research (Cameron et al, 2002) in order to retest their findings and examine the role of communication modality in inoculation. Persuasive message generated statistically significant effects- attitude towards abortion was significantly changed. Both resistance strategies, on the other hand, failed to elicit resistance and measured attitude change wasn't significantly related to communication channel.

Due to the unceasing progress in design of novel emulsifiers, powerful influence of the ongoing ‘green’ trends in cosmetic industry, but also global environmental concerns, there is an increasing demand in development and application of natural-origin, biodegradable and skin-friendly emulsifiers. The present work aims to provide a deeper insight into the group of alkyl polyglucoside emulsifiers and their prospective impact on drug percutaneous permeation. Complexity of the observed lamellar liquid crystal and lamellar gel phases, which represent the basic mechanism of physical stabilisation by the alkyl polyglucosides, entails a comprehensive physicochemical evaluation of any alkyl polyglucoside-based prospective vehicle, prior to assessing its impact on skin absorption. Research conducted so far has suggested several possible mechanisms of alkyl polyglucoside-mediated percutaneous penetration enhancement, which are carefully elaborated throughout the chapter: (1) the observed similarity between the aforementioned complex structures which dominate alkyl polyglucoside-stabilised systems and the inherent stratum corneum lipid ordering could enhance penetration due to the optimal balance between their order and fluidity, (2) the observed complex colloidal structure may lead to diverse modes of water distribution within these systems, providing sustained skin hydration and hence improved skin permeability, and/or (3) the impact on a drug’s thermodynamic activity, easily tailored by the addition of various co-solvents/potential penetration enhancers.

Antimicrobial activity of Usnea barbata especially against bacteria involved in pathogenesis of various skin conditions has been well documented in literature. Nevertheless, there are no papers dealing with formulation of its isolates into topical preparations for treatment of skin infections. In present study, alkyl polyglucoside (APG)-based vehicle was developed as carrier of U. barbata CO2-supercritical extract (U-SE) that demonstrated the best anti- microbial potential in preliminary screening. For comparison, chosen extract in the same concentration and using the same procedure was incorporated into a pharmacopoeial vehicle. Comparative evaluation of physicochemical stability, efficiency and safety proved APG-based vehicle to possess certain preferential features as carrier of U-SE compared to the reference one, composing a topical formulation with potential clinical relevance in treatment of skin infections. Antimikrobna aktivnost vrste Usnea barbata naročito protiv bakterija koje učestvuju u patogenezi različitih bolesti kože, dobro je dokumentovana u naučnoj literaturi. Uprkos tome, ne postoje radovi koji se bave formulacijom topikalnih preparata na bazi ovog lišaja namenjenih lečenju kožnih infekcija. U ovoj studiji, razvijena je podloga stablizovana alkil poliglukozidnim (APG) emulgatorom, kao potencijalni nosač za ekstrakt vrste U. barbata koji je pokazao najbolji antimikrobni potencijal u preliminarnom istraživanju nekoliko ekstrakata dobijenih upotrebom različitih ekstragenasa/postupaka. Radi poređenja, odabrani CO2-natkritični ekstrakt je inkorporiran u istoj koncentraciji (koja odgovara 2 mas.% usninske kiseline) i istim postupkom izrade u često korišćenu podlogu farmakopejskog kvaliteta, a zatim je sprovedeno uporedno istraživanje fizičko-hemijske stabilnosti, efikasnosti i bezbednosti na obe grupe uzoraka. Rezulati našeg istraživanja pokazali su da se razvijena podloga stabilizovana APG emulgatorom može smatrati pogodnim nosačem za CO2-natkritični ekstrakt vrste U. barbata, čineći topikalnu formulaciju sa potencijalnim kliničkim značajem u terapiji kožnih infekcija. Reološka istraživanja pokazala su zadovoljavajuću sposobnost emulzije stabilizovane APG emulgatorom da ostane fizički stabilna nakon dodatka CO2-natkritičnog ekstrakta vrste U. barbata, u poređenju sa farmakopejskom. Međutim, konduktometrijska merenja su pokazala određena neslaganja sa reološkim nala- zima, namećući potrebu za dodatnim istraživanjima radi konačne procene fizičke stabilnosti testiranih emulzionih sistema. Izmerene vrednosti pH tokom perioda od 90 dana čuvanja uzoraka na sobnoj temperaturi ukazale su na zadovoljavajuću preliminarnu hemijsku stabilnost svih uzoraka. Dalja istraživanja efikasnosti i bezbednosti pokazala su bolji antimikrobni potencijal uzoraka sa podlogom stabilizovanom APG emulgatorom u odnosu na tradicionalno upotrebljavanu farmakopejsku bazu poznatog kvaliteta. Zadovoljavajući preliminarni bezbedonosni profili su pokazani kako za uzorke stabilizovane APG emulgatorom tako i za referentne krem uzorke. Na osnovu navedenog, može se zaključiti da je istraživana podloga bazirana na APG emulgatoru pokazala određene povoljnije karakteristike kao nosač za CO2-natkritični ekstrakt vrste U. barbata u poređenju sa konvencionalno korišćenom podlogom, naročito uzimajući u obzir njene poboljšane senzorne karakteristike, kao osobinu koja je često odlučujuća za komplijansu pacijenata.

Emulsions need to fulfil many demands and expectations regarding stability, safety and efficacy on the one hand, and sensory properties on the other, in order to be acceptable to consumers. For stability and sensory properties in particular, rheology, textural analysis and sensory evaluation are important. In this chapter, three case studies are presented showing the possible use of these techniques in various fields, as well as possible substitution of one technique with another. Examples show that certain sensory characteristics can be predicted to some extent by instrumental, rheological and textural measurements. A combination of instrumental tools and simplified sensory studies could be used to characterize a consumer-satisfying Alkyl Polyglucoside-based emulsion product in order to achieve adequate results in a shorter time with less expense.

When formulating topical drugs, research and development departments usually create preparations containing only essential components, while the cosmetic industry formulates more complex vehicles. This chapter reviews Alkyl Polyglucoside-related studies on the formulation of topical preparations. Some APG surfactants form liquid crystalline phases, and other excipients may become components of these mesophases, affecting self-assembly processes prior to liquid crystalline phase formation. Co-stabilization of APG-based systems with lipophilic and hydrophilic stabilizers has been attempted. Some novel APG co-surfactants have also been introduced. Oils of different polarity have been investigated, either as the single component of the oil phase or in complex mixtures. Finally, since many entities intended for topical application are poorly water-soluble, suitable co-solvents, preferably also acting as penetration enhancers, are discussed in detail.

Emulsion systems are the most common vehicles for topical drugs/cosmetic actives. Absence of skin irritation potential is an important legislative requirement. Overcoming emulsion irritancy is usually achieved by selection of emulsifiers. Alkyl Polyglucoside (APG) emulsifiers, successfully used in cosmetics and popularly labelled as skin- and environmentally friendly, have attracted considerable interest. Non-invasive measurements of biophysical skin parameters, and approved in vitro methods, are used for reliable and objective determination of skin properties. This chapter discusses assessment of the performance of topical emulsions, particularly those based on APG-mixed emulsifiers, and interpretation of the results. Research into the safety and efficacy of APGs indicates that APG surfactants could be used for tailoring mild emulsion vehicles, showing benefits as carriers for actives with an unfavourable skin irritation profile.

Surfactants play an important role in the development of colloidal delivery systems for cosmetics and pharmaceutical ingredients. Alkyl Polyglucosides (APGs) show peculiar physicochemical behaviour, which affects their interfacial properties. For example, the phase behaviour of APG/water systems is only slightly influenced by temperature. Hence, no temperature-dependent phase inversion occurs in APG-containing emulsions. They may form thermotropic liquid crystalline phases on heating, and lyotropic liquid crystalline phases on addition of a solvent. In lyotropic liquid crystals, increasing alkyl chain length leads to destabilization of the hexagonal phase in favour of the lamellar one, which is interesting for pharmaceutical systems. The addition of fatty alcohol to APG/water mixtures leads to the appearance of different lamellar phases. Characteristics of APG-mediated systems will be discussed in this chapter.

Skin permeation and penetration assessment is important not only for determining efficacy of a topical product, but also when comparing different formulations during development. This chapter reviews methods for dermal availability assessment of delivery systems, with their advantages and shortcomings, and examples of their practical application with Alkyl Polyglucoside-based preparations. Alkyl Polyglucosides are used in many different delivery systems with various model actives. Systems stabilized with Alkyl Polyglucoside surfactants provide highly satisfactory cutaneous delivery compared with reference samples. This is mainly attributed to the characteristic APG-based colloidal structure and its ability to provide a combined enhancing effect with co-solvents. Microemulsions for dermal/transdermal delivery are also becoming popular due to their high solubilization potential. Alkyl Polyglucoside surfactants are also being considered for development of nanosystems.

Mesomorphic behavior of the novel long-chain alkyl polyglucoside emulsifier comprising arachidyl alcohol (C-20), behenyl alcohol (C-22), and arachidyl glucoside was investigated in order to determine the prevalent stabilization mechanism and moisturizing capacity of emulsion systems based on it. For this to be accomplished thermoanalytical methods (differential scanning calorimetry and thermogravimetric analysis) coupled with microscopy, rheological, X-ray diffraction methods and a short-term in vivo study of skin hydration level were performed. Obtained results have proved that C-20/C-22 alkyl polyglucoside mixed emulsifier is able to provide the synergism between the two main types of lamellar phases, the liquid-crystalline (L alpha), and the gel crystalline (L beta) one, building the emulsion systems of different stability and performance. Formation of lamellar structures influenced for more than one half of water within the system to be entrapped. Conducted investigation of hydration potential in real-time conditions provided valuable information on the investigated emulsion vehicles' moisturizing potential as well as their contribution to the skin barrier improvement. Therefore, it could be expected that emulsions based on this alkyl polyglucoside emulsifier could influence the delivery of active ingredients of both the lipophilic and hydrophilic type. The employment of thermoanalytical methods in our work suggests the possibility for thermal methods to be used more frequently in the characterization of both the novel raw materials and the belonging emulsion systems.

Context: Alkyl polyglucoside surfactants (APG) remain prominent natural origin stabilizers offering a prospect of combining satisfactory stability with mild dermatological properties and complete biodegradability. Objective: With the purpose of adjusting the dose to a patient's needs, dilution of commercial corticosteroid formulations is a practice which may modify efficacy uncontrolledly. The rational of the study was to investigate whether a simple change in ready-to-use bases (co-solvent addition) could address these needs in a more predictive manner. Methods: Hydrocortisone (HC) delivery from such emulsion systems was comparatively assessed employing two in vivo methods: the established human skin blanching assay versus skin stripping technique. Results: HC permeation data obtained after three dose durations showed better overall performance of the APG-stabilized bases relative to reference ones. Although the solubility study showed that all the assessed active samples retained equal thermodynamic activity, diverse HC permeation/penetration implies the importance of the applied base's colloidal structure and/or changes endured. Isopropyl alcohol (IPA) addition offered faster drug penetration enhancement, while glycerol as a moisturizing agent influenced HC penetration through the increase in skin hydration. Conclusion: Although the performed in vivo methods cannot be considered alternative, skin stripping technique proved to be a cost-efficient mode of percutaneous penetration assessment, providing additional information on vehicle-skin interactions.

A wide range of regulatory standards applicable to production and use of tissues, cells, and other biologics (or biologicals), as advanced therapies, indicates considerable interest in the regulation of these products. The objective of this study was to analyze and compare high-tier documents within the Australian, European, and U.S. biologic drug regulatory environments using qualitative methodology. Eighteen high-tier documents from the European Medicines Agency (EMA), U.S. Food and Drug Administration (FDA), and Therapeutic Goods Administration (TGA) regulatory frameworks were subject to automated text analysis. Selected documents were consistent with the legal requirements for manufacturing and use of biologic drugs in humans and fall into six different categories. Concepts, themes, and their co-occurrence were identified and compared. The most frequent concepts in TGA, FDA, and EMA frameworks were “biological,” “product,” and “medicinal,” respectively. This was consistent with the previous manual terminology search. Good Manufacturing Practice documents, across frameworks, identified “quality” and “appropriate” as main concepts, whereas in Good Clinical Practice (GCP) documents it was “clinical,” followed by “trial,” “subjects,” “sponsor,” and “data.” GCP documents displayed considerably higher concordance between different regulatory frameworks, as demonstrated by a smaller number of concepts, similar size, and similar distance between them. Although high-tier documents often use different terminology, they share concepts and themes. This paper may be a modest contribution to the recognition of similarities and differences between analyzed regulatory documents. It may also fill the literature gap and provide some foundation for future comparative research of biologic drug regulations on a global level.

Recently, healthcare professionals again began realizing the benefits of preparing customized medications to meet specific patient needs. The objective of this work was to develop and evaluate simple pharmaceutical bases stabilized with natural-origin surfactant of alkyl polyglucoside (APG) type as prospective ready-to-use bases and compare them to widely used pharmacopoeial ones. Additionally, the ability of the formulated bases to sustain isopropyl alcohol was assessed as well as its influence on ketoprofen skin absorption (as a co-solvent and potential penetration enhancer). In order to evaluate the manifold characteristics a topical drug product should possess, a comprehensive characterization was performed using different techniques. Physicochemical characterization demonstrated satisfactory physical stability of APG-stabilized bases upon the addition of alcohol. In vitro release/permeation studies failed to show significant difference in ketoprofen liberation/permeation profiles from different bases. However, the extent of ketoprofen delivery in vivo was clearly increased from APG bases, relative to that obtained from pharmacopoeia quality one, implying a distinct influence of the emulsion systems' colloidal structures. Taking also into account the rheological behavior of APG bases, revealing their ameliorated sensory characteristics, it could be concluded that the investigated APG bases could be considered as preferential option in drug compounding related to the conventional ones.

Background: The potential for use of chitosan-treated alginate microparticles as a vehicle for oral phenytoin delivery has not been thoroughly exploited. Aim: We studied the influence of preparation procedure and chitosan type on physicochemical properties and release behavior of alginate-chitosan microparticles. Method: The total number of 24 microparticles formulations prepared by varying contents of calcium gelling ions and varying contents and type of chitosan was examined. As an additional variable, two different hardening times (1 and 24 hours) were employed. Possible interactions of components, surface morphology of microparticles as well as release profile of phenytoin were studied. Results: Both series of formulations with regard to hardening times, irrespective of the chitosan type and/or concentration employed appeared to be highly loaded with the model drug (above 90%). The drug release studies showed that the kinetics of phenytoin cannot be straightforwardly predicted based on the molecular weight of chitosan alone. On the other hand, prolonging the hardening time from 1 to 24 hours had significantly improved phenytoin kinetics, and gave rise to a formulation with the liberation half-time of about 2.5 hours. Conclusion: This study showed that the latter formulation is eligible for further modifications aimed at improving the regularity of phenytoin absorption.

The aim of this study was to examine the lyotropic potential of an alkylpolyglucoside mixed emulsifier (Cetearyl glucoside&Cetearyl alcohol), which belongs to the new generation of natural (sugar) surfactants, and to elaborate the potential stabilization mechanism and relation between the colloid microstructure and water distribution within the systems. Polarization and ordinary light as well as transmission electron microscopy, wide and small-angle X-ray diffraction, thermal analysis and rheological measurement were employed for the systems characterization. It was suggested that Cetearyl glucoside&Cetearyl alcohol stabilizes the o/w creams by synergistic effects of viscoelastic hydrophilic gel of lamellar type and lipophilic gel network built up from cetostearyl alcohol semi-hydrates as well as by lamellar liquid crystalline bilayers surrounding the oil droplets. The hydrophilic gel consists of mixed cetearyl glucoside/cetearyl alcohol crystalline bilayers entrapping the water interlamellarly by hydrogen bonding. It is also showed that oil addition into the chosen binary system influences the creams microstructure significantly, which particularly reflects onto the mode of water distribution within the creams and consequently their potential of skin hydration.