Centring participant experience: a realist evaluation of a menstruator-friendly facility design project in a refugee settlement, Lebanon.

INTRODUCTION: Menstrual health in humanitarian contexts is a neglected topic. Its taboo nature presents difficulties for participants in menstrual health projects in these particularly challenging settings. Namely, their experiences may be concealed or overlooked in projects that are typically outcome focused. Realist Evaluation is a useful method to unearth and explore the hidden mechanisms and their causes, which lead to positive or negative participant experiences. The authors have applied this approach to a robust humanitarian menstrual health project to explore how to centre the emotional wellbeing of participants at all stages: prior to, during, and post-participation. STUDY SETTING: The project studied was led by the International Federation of Red Cross and Red Crescent Societies who piloted their adaptable manual for menstruator-friendly water, sanitation and hygiene (WaSH) facility design in humanitarian contexts. It was conducted by the Lebanese Red Cross in an informal tented settlement hosting Syrian refugees in Qaa, Lebanon. METHODS: The authors collected interview and focus group data on the contextual factors and processes within the project from nine project staff and 16 settlement inhabitants. They used a realist process of theory development, testing, and consolidation to understand how and under what circumstances the project inputs affected participants' wellbeing. RESULTS: The contextual factors and causal mechanisms promoting participant experience comprised individual (choices influencing and experience during participation), interpersonal (group dynamics and the role of non-menstruators), and organisational (expertise and knowledge, relationship to participants and cultural differences) factors. IMPLICATIONS: The research uses a case study from a renowned humanitarian organisation who provided a well-delivered project in a conducive environment to explore the mechanisms and contexts that can promote wider learning and refine understanding and programming in this under-researched and -theorised space. Specifically, it informs which contextual factors and project inputs must be present within a menstrual health project to ensure participant satisfaction whilst efficiently delivering well-designed menstruator-friendly WaSH facilities.

Randomized clinical study of injectable dextrin-based hydrogel as a carrier of a synthetic bone substitute.

OBJECTIVES: This study aimed to improve the performance and mode of administration of a glass-reinforced hydroxyapatite synthetic bone substitute, Bonelike by Biosckin® (BL®), by association with a dextrin-based hydrogel, DEXGEL, to achieve an injectable and moldable device named DEXGEL Bone. METHODS: Twelve participants requiring pre-molar tooth extraction and implant placement were enrolled in this study. BL® granules (250-500 µm) were administered to 6 randomized participants whereas the other 6 received DEXGEL Bone. After 6 months, a bone biopsy of the grafted area was collected for histological and histomorphometric evaluation, prior to implant placement. The performance of DEXGEL Bone and BL® treatments on alveolar preservation were further analyzed by computed tomography and Hounsfield density analysis. Primary implant stability was analyzed by implant stability coefficient technique. RESULTS: The healing of defects was free of any local or systemic complications. Both treatments showed good osseointegration with no signs of adverse reaction. DEXGEL Bone exhibited increased granule resorption (p = 0.029) accompanied by a tendency for more new bone ingrowth (although not statistically significant) compared to the BL® group. The addition of DEXGEL to BL® granules did not compromise bone volume or density, being even beneficial for implant primary stability (p = 0.017). CONCLUSIONS: The hydrogel-reinforced biomaterial exhibited an easier handling, a better defect filling, and benefits in implant stability. CLINICAL RELEVANCE: This study validates DEXGEL Bone safety and performance as an injectable carrier of granular bone substitutes for alveolar ridge preservation. TRIAL REGISTRATION: European Databank on Medical Devices (EUDAMED) No. CIV-PT-18-01-02,705; Registo Nacional de Estudos Clínicos, RNEC, No. 30122.

Effects of Different Irrigation Regimes, Nitrogen Levels and Storage Conditions on Volatiles of 'Gala' Apple.

With a characteristic flavour and aroma, "Maçã de Alcobaça" are apples produced in the western region of the mainland of Portugal. Given the known influence of pre-harvest cultural techniques and post-harvest conservation methods on fruit quality, this work evaluated the effect of cultural factors and conservation methods on the volatile profile of 'Gala' apples. Tests were carried out during four seasons (2018 to 2021) in two 'Gala' apple orchards (F and S) maintained with different irrigation rates and nitrogen fertilisation [normal irrigation and normal nitrogen (Control, NINN), normal irrigation and excess nitrogen (NIEN), excess irrigation and normal nitrogen (EINN), excess irrigation and excess nitrogen (EIEN)], and under three storage conditions [Controlled Atmosphere + 1-methylcyclopropene (CA+1-MCP), Dynamic Controlled Atmosphere (DCA) and DCA+1-MCP]. The intact fruit volatiles were isolated by headspace solid-phase microextraction (HS-SPME) and analysed by Gas Chromatography with Flame Ionisation Detection and Gas Chromatography-Mass Spectrometry at harvest (T0) and after 8 months of storage (T8). HS-SPME volatiles from 'Gala' apples, obtained at T0 in control conditions, were characterised by trans,trans-α-farnesene dominance (36-69%), followed by hexyl acetate (5-23%) and hexyl hexanoate (3-9%). The four irrigation and nitrogen treatments did not evidence main changes in the apple volatile profile. Instead, storage conditions changed the ratio between compounds; previously undetected compounds attained high percentages and decreased the intensity of the dominant compounds in the control conditions. Although all storage conditions tested changed the volatile profile and emanation intensity, the effect was more accentuated in storage for 8 months with DCA+1-MCP.

Volatile Profile of Portuguese Monofloral Honeys: Significance in Botanical Origin Determination.

The volatile profiles of 51 samples from 12 monofloral-labelled Portuguese honey types were assessed. Honeys of bell heather, carob tree, chestnut, eucalyptus, incense, lavender, orange, rape, raspberry, rosemary, sunflower and strawberry tree were collected from several regions from mainland Portugal and from the Azores Islands. When available, the corresponding flower volatiles were comparatively evaluated. Honey volatiles were isolated using two different extraction methods, solid-phase microextraction (SPME) and hydrodistillation (HD), with HD proving to be more effective in the number of volatiles extracted. Agglomerative cluster analysis of honey HD volatiles evidenced two main clusters, one of which had nine sub-clusters. Components grouped by biosynthetic pathway defined alkanes and fatty acids as dominant, namely n-nonadecane, n-heneicosane, n-tricosane and n-pentacosane and palmitic, linoleic and oleic acids. Oxygen-containing monoterpenes, such as cis- and trans-linalool oxide (furanoid), hotrienol and the apocarotenoid α-isophorone, were also present in lower amounts. Aromatic amino acid derivatives were also identified, namely benzene acetaldehyde and 3,4,5-trimethylphenol. Fully grown classification tree analysis allowed the identification of the most relevant volatiles for discriminating the different honey types. Twelve volatile compounds were enough to fully discriminate eleven honey types (92%) according to the botanical origin.

Honey Volatiles as a Fingerprint for Botanical Origin-A Review on their Occurrence on Monofloral Honeys.

Honeys have specific organoleptic characteristics, with nutritional and health benefits, being highly appreciated by consumers, not only in food but also in the pharmaceutical and cosmetic industries. Honey composition varies between regions according to the surrounding flora, enabling its characterization by source or type. Monofloral honeys may reach higher market values than multifloral ones. Honey's aroma is very specific, resulting from the combination of volatile compounds present in low concentrations. The authentication of honey's complex matrix, according to its botanical and/or geographical origin, represents a challenge nowadays, due to the different sorts of adulteration that may occur, leading to the search for reliable marker compounds for the different monofloral honeys. The existing information on the volatiles of monofloral honeys is scarce and disperse. In this review, twenty monofloral honeys and honeydews, from acacia, buckwheat, chestnut, clover, cotton, dandelion, eucalyptus, fir tree, heather, lavender, lime tree, orange, pine, rape, raspberry, rhododendron, rosemary, strawberry tree, sunflower and thyme, were selected for volatile comparison purposes. Taking into consideration the country of origin, the technique of isolation and analysis, the five main volatiles from each of the honeys are compared. Whereas some compounds were found in several types of monofloral honey, and thus not considered good volatile markers, some monofloral honeys revealed characteristic volatile compounds independently of their provenance.

Development of a dextrin-vitamin D3 micelle nanocarrier for the antimicrobial peptide LLKKK18 as a potential therapeutic agent for bone infections.

In this work, an expedite synthesis was developed for a self-assembled micelle carrier for the antimicrobial peptide LL18. Covalent one-pot functionalization of dextrin with succinylated vitamin D3 and succinic anhydride produced an amphiphilic material that undergoes self-assembly into micelles in aqueous medium. Succinylated dextrin-vitamin D3 micelles were efficiently loaded with LL18 by electrostatic and hydrophobic interactions. Remarkably, the LL18-loaded micelle formulation dramatically improves the antibacterial activity of free LL18 against S. aureus, completely abrogates its severe hemolytic activity, redirects the internalization of LL18 from the perinuclear region of osteoblasts to the lysosomes and reduces cellular toxicity towards osteoblasts and macrophages. Overall, this work demonstrates that self-assembled micelle formulations based on dextrin, vitamin D3 and antimicrobial peptides, are promising platforms to develop multifunctional antibiotic-independent antimicrobial agents, not prone to the development of bacterial resistance, to treat bone infections.

Coriander (Coriandrum sativum L.) from Alentejo (South Portugal)-Ethnobotany and Potential Industrial Use.

Coriander is a medicinal and aromatic plant (MAP) traditionally cultivated and used in Alentejo, Portugal. However, few publications are available about its ethnobotanical applications. Four independent ethnobotanical surveys were carried out: throughout the region (2002-2003), in three villages (2013), and in city markets (2007 and 2022). Coriander was the most common fresh cultivated MAP (75% of the total area) and also the most representative MAP fresh herb in city markets. The leaves, mostly, were used fresh or frozen or transformed in piso. Some of the recipes have agro-industrial potential, such as piso and aromatized olive oil. Coriander essential oils (EOs) were isolated by hydrodistillation from aerial parts with inflorescence emergence (APIs) and from fruits, and fatty acids (FA) by solvent extraction from the fruits. Gas chromatography and gas chromatography-mass spectrometry analysis showed EOs dominated by n-decanal (21-24%), 2-trans-decenal (12-18%) and n-nonane (10-17%) in APIs, and linalool dominance (73-78%) in the fruits. Petroselinic acid (32-55%) was the dominant fatty acid. A literature survey on conventional and nonconventional extraction techniques showed a constancy in the dominant compounds isolated, highlighted piso as a home-made green-extraction procedure, but also reflected the relevance of coriander as a MAP with diverse industrial potential uses.

Encapsulation of DNA in macroscopic and nanosized calcium alginate gel particles.

Calcium alginate beads, which are biodegradable and biocompatible, have been widely employed as delivery matrices for biomacromolecules. In the present work, the feasibility of encapsulation of DNA (which is used as a model biomacromolecule) in calcium alginate nanobeads (sub-200 nm size), prepared using a recently developed protocol based on the phase inversion temperature (PIT) emulsification method [Machado et al. Langmuir 2012, 28, 4131-4141], was assessed. The properties of the nanobeads were compared to those of the corresponding macroscopic (millimeter sized) calcium alginate beads. It was found that DNA, representing a relatively stiff and highly charged polyanion (thus like-charged to alginate), could be efficiently encapsulated in both nanosized and macroscopic beads, with encapsulation yields in the range of 77-99%. Complete release of DNA from the beads could be accomplished on dissolution of the gel by addition of a calcium-chelating agent. Importantly, the DNA was not denatured or fragmented during the preparation and collection of the nanobeads, which are good indicators of the mildness of the preparation protocol used. The calcium alginate nanobeads prepared by the herein utilized protocol thus show good potential to be used as carriers of sensitive biomacromolecules.

The ice age - A review on formulation of Adeno-associated virus therapeutics.

Gene therapies offer promising therapeutic alternatives for many disorders that currently lack efficient treatment options. Due to their chemical nature and physico-chemical properties, delivery of polynucleic acids into target cells and subcellular compartments remains a significant challenge. Adeno-associated viruses (AAV) have gained a lot of interest for the efficient delivery of therapeutic single-stranded DNA (ssDNA) genomes over the past decades. More than a hundred products have been tested in clinical settings and three products have received market authorization by the US FDA in recent years. A lot of effort is being made to generate potent recombinant AAV (rAAV) vectors that show favorable safety and immunogenicity profiles for either local or systemic administration. Manufacturing processes are gradually being optimized to deliver a consistently high product quality and to serve potential market needs beyond rare indications. In contrast to protein therapeutics, most rAAV products are still supplied as frozen liquids within rather simple formulation buffers to enable sufficient product shelf life, significantly hampering global distribution and access. In this review, we aim to outline the hurdles of rAAV drug product development and discuss critical formulation and composition aspects of rAAV products under clinical evaluation. Further, we highlight recent development efforts in order to achieve stable liquid or lyophilized products. This review therefore provides a comprehensive overview on current state-of-the-art rAAV formulations and can further serve as a map for rational formulation development activities in the future.

Essential Oils from Origanum vulgare subsp. virens (Hoffmanns. & Link) Ietsw. Grown in Portugal: Chemical Diversity and Relevance of Chemical Descriptors.

Origanum vulgare L. is a well-known aromatic and medicinal plant, whose essential oil (EO) has recognised flavouring and medicinal properties. In this study, Origanum vulgare subsp. virens (Hoffmanns. & Link) Ietsw. EOs, isolated from accessions grown in experimental fields, were evaluated. The plant material was grown from rooted cuttings or nutlets (fruits), originally collected in 20 regions in mainland Portugal and harvesting for EO isolation was performed in two years. EOs were isolated by hydrodistillation and analysed by gas chromatography and gas chromatography-mass spectrometry, for EO quantification and identification, respectively. EO yields ranged from <0.05-3.3% for rooted cuttings, with oregano samples obtained in Portalegre and Alandroal, respectively. Ninety-one compounds were identified, mainly grouped in oxygen-containing monoterpenes and monoterpene hydrocarbons. EO agglomerative cluster analysis evidenced two main clusters, with the first subdivided into four subclusters. From the obtained data, the putative O. vulgare subsp. virens chemotypes are carvacrol, thymol and linalool, with γ-terpinene, p-cymene, cis- and trans-ß-ocimene also contributing as these EOs chemical descriptors. The comparison between the present data and a survey of the existing literature on Portuguese O. vulgare reinforces the major variability of this species' EOs and emphasises the importance of avoiding wild collections to obtain a defined chemical type of crop production of market relevance.

Chemical Variability of the Essential Oils from Two Portuguese Apiaceae: Coriandrum sativum L. and Foeniculum vulgare Mill.

Coriandrum sativum L. and Foeniculum vulgare Mill. are two aromatic and medicinal Apiaceae species commonly grown in Portugal, whose essential oils (EOs) are used in the food, pharmaceutical, and cosmetics industries. The present study evaluated EOs isolated from the fruits and vegetative aerial parts (VAPs) of 11 samples of Coriandrum sativum L. and from the fruits of 19 samples of Foeniculum vulgare Mill. The plant material was grown in experimental fields, after collection from several regions of mainland Portugal. The EOs were isolated by hydrodistillation and analyzed by gas chromatography and gas chromatography-mass spectrometry. The coriander EOs analysis evidenced two main clusters, with the first containing the fruits' EOs dominated by linalool (60-73%), γ-terpinene, and α-pinene and the second with the VAPs' EOs, which showed 2-trans-decenal (37-63%) and n-decanal (13-30%) as the main compounds. The fennel EOs analysis revealed two well correlated clusters, the first dominated by estragole (34-76%) and fenchone (16-30%) and the other dominated by trans-anethole (37-56%) and fenchone (14-34%). The present data suggest coriander EOs' chemical descriptors as linalool for the fruits' EOs and 2-trans-decenal with n-decanal for the VAPs' EOs. For the fennel fruit EOs, the putative descriptors were trans-anethole and estragole, with variable fenchone content. The gathered data reinforce the relevance of clarifying variability of these species' EOs, particularly when considering aromatic and medicinal plants with such a wide range of applications.

Preparation of calcium alginate nanoparticles using water-in-oil (W/O) nanoemulsions.

A procedure for the preparation of calcium alginate nanoparticles in the aqueous phase of water-in-oil (W/O) nanoemulsions was developed. The emulsions were produced from mixtures of the nonionic surfactant tetraethylene glycol monododecyl ether (C(12)E(4)), decane, and aqueous solutions of up to 2 wt % sodium alginate by means of the phase inversion temperature (PIT) emulsification method. This method allows the preparation of finely dispersed emulsions without a large input of mechanical energy. With alginate concentrations of 1-2 wt % in the aqueous phase, emulsions showed good stability against Ostwald ripening and narrow, monomodal distributions of droplets with radii <100 nm. Gelation of the alginate was induced by the addition of aqueous CaCl(2) to the emulsions under stirring, and particles formed were collected using a simple procedure based on extraction of the surfactant on addition of excess oil. The final particles were characterized using cryo-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS). They were found to be essentially spherical with a homogeneous interior, and their size was similar to that of the initial emulsion droplets. The herein presented "low-energy" method for preparation of biocompatible nanoparticles has the potential to be used in various applications, e.g., for the encapsulation of sensitive biomacromolecules.

Injectable hydrogel as a carrier of vancomycin and a cathelicidin-derived peptide for osteomyelitis treatment.

A local drug delivery system that attempts to find a suitable balance between antimicrobial and regenerative actions was developed for osteomyelitis treatment (OM). This system combines the angiogenic and immunomodulatory peptide LLKKK18 (LL18) and vancomycin hydrochloride (VH), loaded into an injectable oxidized dextrin (ODEX)-based hydrogel (HG). In vitro cytotoxicity was analyzed in MC3T3-E1 pre-osteoblasts and erythrocytes. The kinetics of LL18 release was studied. Antimicrobial activity was assessed in vitro against a clinical Methicillin-Resistant Staphylococcus aureus (MRSA) strain. A rat model of acute OM was developed by direct inoculation into a tibia defect, concomitantly with the implantation of the drug-loaded HG. The local bioburden was quantified and damage in surrounding tissues was examined histologically. In vitro, ODEX-based HG displayed a safe hemolytic profile. Half of LL18 (53%) is released during the swelling phase at physiological pH, then being gradually released until complete HG degradation. LL18-loaded HG at 300 µM was the most effective peptide formulation in decreasing in vivo infection among concentrations ranging from 86 to 429 µM. The histopathological scores observed in vivo varied with the LL18 concentration in a dose-dependent manner. VH at 28 mM completely eradicated bacteria, although with substantial tissue injury. We have found that sub-millimolar doses of VH combined with LL18 at 300 µM may suffice to eradicate the infection, with reduced tissue damage. We propose an easy-to-handle, shape-fitting HG formulation with the potential to treat MRSA-infected bone with low VH doses associated with LL18.

Quality assessment of Portuguese monofloral honeys. Physicochemical parameters as tools in botanical source differentiation.

The quality evaluation and physicochemical parameters assessment of Portuguese monofloral honeys were performed. Fifty-one monofloral honeys were collected from several regions from mainland Portugal, and from the Azores islands, producer labelled as carob tree (n = 5), chestnut (n = 2), eucalyptus (n = 5), bell heather (n = 6), incense (n = 4), lavender (n = 8), orange (n = 9), rape (n = 2), raspberry (n = 2), rosemary (n = 1), sunflower (n = 3), and strawberry tree (n = 4). Pollen analysis and microbiological safety were evaluated, and the parameters such as colour index, moisture content, electrical conductivity, hydroxymethylfurfural, pH, free and total acidity, diastase activity, proline, and sugar profile were assessed for physicochemical characterization, in all 51 monofloral honeys. After melissopalynological examination, the honeys were either confirmed as monofloral, or classified as multifloral with predominance of a specific pollen type or multifloral. Microbiological analysis showed that honeys were safe for human consumption. Pairwise comparisons of physicochemical parameters, using only honey types with n ≥ 3, revealed significant differences between honey types. Despite some homogeneity in sugar profile among honeys, eucalyptus honey was significantly different in glucose, maltose and maltulose content compared to incense, orange and sunflower honeys, and also exhibited a higher isomaltose amount compared to all analyzed honeys. Electrical conductivity, colour index, free and total acidity, and diastase activity showed significant differences between the analyzed honeys, indicating that these parameters may provide an additional tool in monofloral honey identification.

Unassisted and Carbon Dioxide-Assisted Hydro- and Steam-Distillation: Modelling Kinetics, Energy Consumption and Chemical and Biological Activities of Volatile Oils.

The demand for more suitable eco-friendly extraction processes has grown over the last few decades and driven research to develop efficient extraction processes with low energy consumption and low costs, but always assuring the quality of the volatile oils (VOs). The present study estimated the kinetic extraction and energy consumption of simultaneous hydro- and steam-distillation (SHSD), and SHSD assisted by carbon dioxide (SHSDACD), using an adopted modelling approach. The two isolation methods influenced the VOs yield, chemical composition and biological activities, namely, antioxidant, anti-glucosidase, anti-acetylcholinesterase and anti-inflammatory properties. SHSDACD provided higher VOs yields than the SHSD at a shorter extraction time: 2.8% at 30 min vs. 2.0% at 120 min, respectively, for Rosmarinus officinalis, 1.5% at 28 min vs. 1.2% at 100 min, respectively, for Lavandula angustifolia, and 1.7% at 20 min vs. 1.6% at 60 min, respectively, for Origanum compactum. The first order and sigmoid model fitted to SHSD and SHSDACD, respectively, with R2 value at 96% and with mean square error (MSE) < 5%, where the k distillation rate constant of SHSDACD was fivefold higher and the energy consumption 10 times lower than the SHSD. The rosemary SHSD and SHSDACD VOs chemical composition were similar and dominated by 1,8-cineole (50% and 48%, respectively), and camphor (15% and 12%, respectively). However, the lavender and oregano SHSDACD VOs were richer in linalyl acetate and carvacrol, respectively, than the SHSD VOs. The SHSDACD VOs generally showed better capacity for scavenging the nitric oxide and superoxide anions free radicals as well as for inhibiting α-glucosidase, acetylcholinesterase, and lipoxygenase.

The roles of vitamin D and cathelicidin in type 1 diabetes susceptibility.

Type 1 diabetes has an increasingly greater incidence and prevalence with no cure available. Vitamin D supplementation is well documented to reduce the risk of developing type 1 diabetes. Being involved in the modulation of cathelicidin expression, the question whether cathelicidin may be one of the underlying cause arises. Cathelicidin has been implicated in both the development and the protection against type 1 diabetes by mediating the interplay between the gut microbiome, the immune system and ß cell function. While its potential on type 1 diabetes treatment seems high, the understanding of its effects is still limited. This review aims to contribute to a more comprehensive understanding of the potential of vitamin D and cathelicidin as adjuvants in type 1 diabetes therapy.

Interactions between DNA and nonionic ethylene oxide surfactants are predominantly repulsive.

In the present work, the interactions between double-stranded (ds) or single-stranded (ss) DNA and nonionic ethylene oxide (EO) surfactants, with special attention to the possible contributions from hydrophobic interactions, have been investigated using a multitechnique approach. It was found that the presence of ss as well as dsDNA induces a slight decrease of the cloud point of pentaethylene glycol monododecyl ether (C(12)E(5)). Assessment of the partitioning of DNA between the surfactant-rich and surfactant-poor phases formed above the cloud point showed that the polymer was preferably located in the surfactant-poor phase. Surface tensiometry experiments revealed that neither of the DNA forms induced surfactant micellization. Finally, it was shown by DNA melting measurements that another EO surfactant (C(12)E(8)) did not affect the relative stabilities of ss and dsDNA. To summarize, all experiments suggest that the net interaction between DNA and nonionic surfactants of the EO type is weakly repulsive, which can be attributed mainly to steric effects. In general, the results were practically identical for the ds and ss forms of DNA, except those from the cloud point experiments, where the decrease of the cloud point was less pronounced with ssDNA. This finding indicates the presence of an attractive component in the interaction, which can reasonably be ascribed to hydrophobic effects.

A diffusing wave spectroscopy study of pharmaceutical emulsions for physical stability assessment.

Emulsions are broadly used in pharmaceutics either as intermediate products or as final dosage forms. Such disperse systems are only kinetically stabilized and therefore early detection of physical instability is highly desirable. This work employed diffusing wave spectroscopy (DWS) to study a series of model emulsions that were categorized, based on their composition, as either "simple" or "complex". DWS data were compared with results of droplet size imaging, apparent viscosity obtained by microfluidics, and near-infrared (NIR) analytical centrifugation. A mathematical model of the droplet mean square displacement (MSD) was modified by us regarding improved fitting of experimental data. Although the emulsions showed different types of instability like creaming and sedimentation, a good rank correlation was found between the DWS parameters and results from the comparative stability methods. Our findings indicate that DWS provides a highly attractive method for stability analysis of pharmaceutical emulsions because it requires only low sample volumes, is rapid and non-invasive. The proposed data modeling provides the means for a better understanding of emulsion microstructure that in turn will help designing quality into pharmaceutical dispersions.

A microstructural study of water effects in lipid-based pharmaceutical formulations for liquid filling of capsules.

Water is known to exhibit pronounced effects on lipid-based formulations (LBFs) and much research has focused on aqueous dispersion and dilution behavior regarding biopharmaceutical performance. From a product quality perspective, it is also critical to study a range of lower water amounts in formulations with respect to capsule filling. The present work addressed the need for a better understanding of LBF microstructure by taking percolation theory into account. The effects of increasing amounts of water on LBFs were analyzed by conductivity, water activity, time-domain nuclear magnetic resonance, and diffusing wave spectroscopy. Results were interpreted using percolation theory and preliminary mechanical tests were conducted on gelatin and hypromellose (HPMC) capsule shells. For both LBF systems, increasing water amounts led to marked changes in the microstructure of the formulations. Percolation laws could be fitted adequately to the data and thresholds were identified for the formation of continuous water channels (ϕwc~0.02-0.06). A new theoretical model was proposed for water activity. The preliminary shell material studies showed that the threshold for generating water channels in the formulation could be correlated to mechanical changes of the capsule shell that were relatively more pronounced in the case of gelatin. This mechanistic study demonstrated the importance of understanding and monitoring of microstructural changes occurring in LBFs with increasing amounts of water, which will help to design quality into the final dosage form.

Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs.

Combining two or more antiretroviral drugs in one medical product is an interesting but challenging strategy for developing topical anti-HIV microbicides. We developed a new vaginal delivery system comprising the incorporation of nanoparticles (NPs) into a polymeric film base - NPs-in-film - and tested its ability to deliver tenofovir (TFV) and efavirenz (EFV). EFV-loaded poly(lactic-co-glycolic acid) NPs were incorporated alongside free TFV into fast dissolving films during film manufacturing. The delivery system was characterized for physicochemical properties, as well as genital distribution, local and systemic 24h pharmacokinetics (PK), and safety upon intravaginal administration to mice. NPs-in-film presented suitable technological, mechanical and cytotoxicity features for vaginal use. Retention of NPs in vivo was enhanced both in vaginal lavages and tissue when associated to film. PK data evidenced that vaginal drug levels rapidly decreased after administration but NPs-in-film were still able to enhance drug concentrations of EFV. Obtained values for area-under-the-curve for EFV were around one log10 higher than those for the free drugs in aqueous vehicle (phosphate buffered saline). Film alone also contributed to higher and more prolonged local drug levels as compared to the administration of TFV and EFV in aqueous vehicle. Systemic exposure to both drugs was low. NPs-in-film was found to be safe upon once daily vaginal administration to mice, with no significant genital histological changes or major alterations in cytokine/chemokine profiles being observed. Overall, the proposed NPs-in-film system seems to be an interesting delivery platform for developing combination vaginal anti-HIV microbicides.