Effects of Sucrose Palmitate on the Physico-Chemical and Mucoadhesive Properties of Buccal Films.

In our current research, sucrose palmitate (SP) was applied as a possible permeation enhancer for buccal use. This route of administration is a novelty as there is no literature on the use of SP in buccal mucoadhesive films. Films containing SP were prepared at different temperatures, with different concentrations of SP and different lengths of hydroxypropyl methylcellulose (HPMC) chains. The mechanical, structural, and in vitro mucoadhesive properties of films containing SP were investigated. Tensile strength and mucoadhesive force were measured with a device and software developed in our Institute. Positron annihilation lifetime spectroscopy (PALS) and X-ray powder diffractometry (XRPD) were applied for the structure analysis of the films. Mucoadhesive work was calculated in two ways: from the measured contact angle and compared with direct mucoadhesive work, which measured mucoadhesive force, which is direct mucoadhesion work. These results correlate linearly with a correlation coefficient of 0.98. It is also novel because it is a new method for the determination of mucoadhesive work.

Preparation and physicochemical characterization of matrix pellets containing APIs with different solubility via extrusion process.

In this study, a multiparticulate matrix system was produced, containing two different active pharmaceutical ingredients (APIs): enalapril-maleate and hydrochlorothiazide. The critical control points of the process were investigated by means of factorial design. Beside the generally used microcrystalline cellulose, ethylcellulose was used as matrix former to achieve modified drug release ensured by diffusion. The matrix pellets were made by extrusion-spheronization using a twin-screw extruder. Some pellet properties (aspect ratio, 10% interval fraction, hardness, deformation process) were determined. The aim of our study was to investigate how the two different APIs with different solubility and particle size influence the process. The amount of the granulation liquid plays a key role in the pellet shaping. A higher liquid feed rate is preferred in the pelletization process.

Matrix tablets based on a carrageenan with the modified-release of sodium riboflavin 5'-phosphate.

The focus of this work was to produce modified-release monolithic matrix tablets containing sodium riboflavin 5'-phosphate (vitamin B2) as active pharmaceutical ingredient (API). Riboflavin 5'-phosphate is absorbed from the upper gastrointestinal tract by a specific transport mechanism. The aim of this work was the development of modified-release tablets from which most or the entire API can dissolve within 5 h. The dissolution was started in medium pH 1.2 (gastric juice) and finished in medium pH 4.5. The matrix former was iota-carrageenan combined with microcrystalline cellulose (MCC) and lactose in different ratios. Factorial design was used in this work so as to study the effects of the MCC/lactose ratio on the parameters of the tablets, and especially on the dissolution process. The dissolution data were subjected to statistical analysis, and the release profiles were fitted with different models. It was found that the MCC/lactose ratio influenced the quality of the tablets to a high degree. The Korsmeyer-Peppas model proved to characterize the total dissolution profile best, but fitting of the separate sections was also possible with a linear model.

Modified-release capsules containing sodium riboflavin 5'-phosphate.

INTRODUCTION: The focus of this work was to produce delayed-release capsules containing riboflavin (vitamin B2, as API) layered pellets. Riboflavin therapy is indicated in patients with a riboflavin deficiency, which usually occurs in conjunction with malabsorption, alcoholism or a protein-calorie deficiency and rarely as the sole vitamin deficiency. Riboflavin is readily absorbed from the upper gastrointestinal tract by a specific transport mechanism. The dissolution rate of coated capsules was controlled through the coating of the capsules and the thickness of the coating layer. METHODS: The core pellets (Cellet 300) were loaded with a 10% aqueous solution of sodium riboflavin 5'-phosphate by a layering technique in a coating pan. Hard capsules were filled with riboflavin layered pellets and coated with Eudragit NE polymer with different coating layer thicknesses. The dissolution was tested in gastric and intestinal fluids with the half-change method. The dissolution profiles were analyzed with the use of different mathematical models and an attempt was made to predict the optimum coating film thickness that ensures the required degree and rate of dissolution. RESULTS: A new solid dosage form was developed which can enhance the bioavailability of riboflavin. RRSBW distribution and the Chapman-Richards growth function were used to fit the dissolution profiles. Statistical analysis indicated that the best products were described by the Chapman-Richards equation. The results were utilized to create a theoretical model suitable for prediction of the optimum film thickness that ensures the required release of riboflavin.

Grassland restoration on linear landscape elements - comparing the effects of topsoil removal and topsoil transfer.

Artificial linear landscape elements, including roads, pipelines, and drainage channels, are main sources of global habitat fragmentation. Restoration of natural habitats on unused linear landscape elements can increase habitat quality and connectivity without interfering with agricultural or industrial development. Despite that topsoil removal and transfer are widely applied methods in restoration projects, up to our knowledge these were previously not compared in the same study system. To address this knowledge gap, we compared spontaneous vegetation recovery after the elimination of positive (embankments) and negative landscape scars (drainage channels) in lowland alkaline landscapes in South Hungary. The novelty of our study is that we compared the fine-scale and landscape-scale results of both methods. At the fine scale, we monitored the spontaneous vegetation development on the created open surfaces in the first, second and fourth year after restoration in 160 permanent plots per year. For characterizing the habitat changes on the landscape scale, we prepared habitat maps and assigned naturalness scores to each patch before and after the restoration activities. Both restoration methods resulted in a rapid vegetation recovery at the fine scale, progressing toward the reference state. In the topsoil removal treatment, a large part of the soil seed bank was removed; therefore, the colonization of the bare surface was a slower process. Seeds of halophytes, including the endemic and protected Suaeda pannonica, were probably present in the deeper soil layers, and these species became established in the restored surfaces, despite being absent in the surrounding vegetation. For restoring vegetation cover, topsoil transfer was a more rapid option; however, vegetation closure and competition by generalist species and weeds hampered the establishment of target species. The removal of the landscape scars by both methods made the sites accessible for grazing. At the landscape scale, the two methods had different effects: there was a slight increase in the habitat naturalness in the topsoil removal site, and a slight decrease in the topsoil transfer site because of weed encroachment. Spreading an upper layer of nutrient-poor soil with low amounts of weed seeds, direct propagule transfer, and targeted grazing regimes could enhance restoration success.

Visually evoked local field potential changes in the caudate nucleus are remarkably more frequent in awake, behaving cats than in anaesthetized animals.

Previous results show that halothane gas anaesthesia has a suppressive effect on the visually evoked single-cell activities in the feline caudate nucleus (CN). In this study, we asked whether the low-frequency neuronal signals, the local field potentials (LFP) are also suppressed in the CN of anaesthetized animals.To answer this question, we compared the LFPs recorded from the CN of two halothane-anaesthetized (1.0%), paralyzed, and two awake, behaving cats during static and dynamic visual stimulation. The behaving animals were trained to perform a visual fixation task.Our results denoted a lower proportion of significant power changes to visual stimulation in the CN of the anesthetized cats in each frequency range (from delta to beta) of the LFPs, except gamma. These differences in power changes were more obvious in static visual stimulation, but still, remarkable differences were found in dynamic stimulation, too. The largest differences were found in the alpha and beta frequency bands for static stimulation. Concerning dynamic stimulation, the differences were the biggest in the theta, alpha and beta bands.Similar to the single-cell activities, remarkable differences were found between the visually evoked LFP changes in the CN of the anaesthetized, paralyzed and awake, behaving cats. The halothane gas anaesthesia and the immobilization suppressed the significant LFP power alterations in the CN to both static and dynamic stimulation. These results suggest the priority of the application of behaving animals even in the analysis of the visually evoked low-frequency electric signals, the LFPs recorded from the CN.

Meso-scale environmental heterogeneity drives plant trait distributions in fragmented dry grasslands.

Environmental heterogeneity shapes the patterns of resources and limiting factors and therefore can be an important driver of plant community composition through the selection of the most adaptive functional traits. In this study, we explored plant trait-environment relationships in environmentally heterogeneous microsite complexes at the meso-scale (few meters), and used ancient Bulgarian and Hungarian burial mounds covered by dry grasslands as a model habitat. We assessed within-site trait variability typical of certain microsites with different combinations of environmental parameters (mound slopes with different aspects, mound tops, and surrounding plain grasslands) using a dataset of 480 vegetation plots. For this we calculated community-weighted means (CWMs) and abundance models. We found that despite their small size, the vegetation on mounds was characterized by different sets of functional traits (higher canopy, higher level of clonality, and heavier seeds) compared to the plain grasslands. North-facing slopes with mild environmental conditions were characterized by perennial species with light seeds, short flowering period, and a high proportion of dwarf shrubs sharply contrasted from the plain grasslands and from the south-facing slopes and mound tops with harsh environmental conditions. Patterns predicted by CWMs and abundance models differed in the case of certain traits (perenniality, canopy height, and leaf dry matter content), suggesting that environmental factors do not necessarily affect trait optima directly, but influence them indirectly through correlating traits. Due to the large relative differences in environmental parameters, contrasts in trait composition among microsites were mostly consistent and independent from the macroclimate. Mounds with high environmental heterogeneity can considerably increase variability in plant functional traits and ecological strategies at the site and landscape levels. The large trait variation on topographically heterogeneous landscape features can increase community resilience against climate change or stochastic disturbances, which underlines their conservation importance.

Automated preprocessing of 64 channel electroenchephalograms recorded by biosemi instruments.

Preprocessing is a mandatory step in electroencephalogram (EEG) signal analysis. Overcoming challenges posed by high noise levels and substantial amplitude artifacts, such as blink-induced electrooculogram (EOG) and muscle-related electromyogram (EMG) interference, is imperative. The signal-to-noise ratio significantly influences the reliability and statistical significance of subsequent analyses. Existing referencing approaches employed in multi-card systems, like using a single electrode or averaging across multiple electrodes, fall short in this respect. In this article, we introduce an innovative referencing method tailored to multi-card instruments, enhancing signal fidelity and analysis outcomes. Our proposed signal processing loop not only mitigates blink-related artifacts but also accurately identifies muscle activity. This work contributes to advancing EEG analysis by providing a robust solution for artifact removal and enhancing data integrity.•Removes blink•Marks muscle activity•Re-references with design specific enhancements.

How to not trade water for carbon with tree planting in water-limited temperate biomes?

The most widespread nature-based solution for mitigating climate change is tree planting. When realized as forest restoration in historically forested biomes, it can efficiently contribute to the sequestration of atmospheric carbon and can also entail significant biodiversity and ecosystem service benefits. Conversely, tree planting in naturally open biomes can have adverse effects, of which water shortage due to increased evapotranspiration is among the most alarming ones. Here we assessed how soil texture affects the strength of the trade-off between tree cover and water balance in the forest-steppe biome, where the global pressure for afforestation is threatening with increasing tree cover above historical levels. Here we monitored vertical soil moisture dynamics in four stands in each of the most common forest types of lowland Hungary on well-drained, sandy (natural poplar groves, and Robinia and pine plantations) and on poorly drained, silty-clayey soils (natural oak stands and Robinia plantations), and neighboring grasslands. We found that forests on sand retain moisture in the topsoil (approx. 20 cm) throughout the year, but a thick dry layer develops below that during the vegetation period, significantly impeding groundwater recharge. Neighboring sandy grasslands showed an opposite pattern, with often dry topsoil but intact moisture reserves below, allowing deep percolation. In contrast, forests on silty-clayey soils did not desiccate lower soil layers compared neighboring grasslands, which in turn showed moisture patterns similar to sandy grasslands. We conclude that, in water-limited temperate biomes where landscape-wide water regime depends on deep percolation, soil texture should drive the spatial allocation of tree-based climate mitigation efforts. On sand, the establishment of new forests should be kept to a minimum and grassland restoration should be preferred. The trade-off between water and carbon is less pronounced on silty-clayey soils, making forest patches and wooded rangelands viable targets for both climate mitigation and ecosystem restoration.

PADAPT 1.0 - the Pannonian Dataset of Plant Traits.

The existing plant trait databases' applicability is limited for studies dealing with the flora and vegetation of the eastern and central part of Europe and for large-scale comparisons across regions, mostly because their geographical data coverage is limited and they incorporate records from several different sources, often from regions with markedly different climatic conditions. These problems motivated the compilation of a regional dataset for the flora of the Pannonian region (Eastern Central Europe). PADAPT, the Pannonian Dataset of Plant Traits relies on regional data sources and collates data on 54 traits and attributes of the plant species of the Pannonian region. The current version covers approximately 90% of the species of the region and consists of 126,337 records on 2745 taxa. By including species of the eastern part of Europe not covered by other databases, PADAPT can facilitate studying the flora and vegetation of the eastern part of the continent. Although data coverage is far from complete, PADAPT meets the longstanding need for a regional database of the Pannonian flora.

Effects of processing on the release profiles of matrix systems containing 5-aminosalicylic acid.

The aim of this study was to investigate the influence of different processing methods on the profiles of 5-aminosalicylic acid dissolution from controlled-release matrix systems based on Eudragit® RL and Eudragit® RS water-insoluble polymers. The pure polymers and their mixtures were studied as matrix formers using different processing methods, i.e., direct compression, wet granulation of the active ingredient with the addition of polymer(s) to the external phase, wet granulation with water, and wet granulation with aqueous dispersions. In comparison with the directly compressed tablets, tablets made by wet granulation with water demonstrated a 6-19% increase in final drug dissolution, whereas when polymers were applied in the external phase during compression, a 0-13% decrease was observed in the amount of drug released. Wet granulation with aqueous polymer dispersions delayed the release of the drug; this was especially marked (a 54-56% decrease in drug release) in compositions, which contained a high amount of Eudragit RL 30D. The release profiles were mostly described by the Korsmeyer-Peppas model or the Hopfenberg model.

Patch and matrix characteristics determine the outcome of ecosystem engineering by mole rats in dry grasslands.

Background: Burrowing mammals are important ecosystem engineers, especially in open ecosystems where they create patches that differ from the surrounding matrix in their structure or ecosystem functions. Methods: We evaluated the fine-scale effects of a subterranean ecosystem engineer, the Lesser blind mole rat on the vegetation composition of sandy dry grasslands in Hungary. In this model system we tested whether the characteristics of the patch (mound size) and the matrix (total vegetation cover in the undisturbed grassland) influence the structural and functional contrasts between the mounds and the undisturbed grasslands. We sampled the vegetation of 80 mounds and 80 undisturbed grassland plots in four sites, where we recorded the total vegetation cover, and the occurrence and cover of each vascular plant species. We used two proxies to characterise the patches (mounds) and the matrix (undisturbed grassland): we measured the perimeter of the mounds and estimated the total vegetation cover of the undisturbed grasslands. First, we compared the vegetation characteristics of the mounds and the surrounding grasslands with general linear models. Second, we characterised the contrasts between the mounds and the undisturbed grassland by relative response indices (RRIs) of the vegetation characteristics studied in the first step. Results: Species composition of the vegetation of the mounds and undisturbed grasslands was well separated in three out of the four study sites. Mounds were characterised by lower vegetation cover, lower cover of perennial graminoids, and higher diversity, and evenness compared to undisturbed grasslands. The contrast in vegetation cover between mounds and undisturbed grasslands increased with decreasing patch size. Increasing vegetation cover in the matrix grasslands increased the contrasts between the mounds and undisturbed grasslands in terms of total cover, perennial graminoid cover, diversity, and evenness. Our results suggest that mole rat mounds provide improved establishment conditions for subordinate species, because they are larger than other types of natural gaps and are characterised by less intense belowground competition. The ecosystem engineering effect, i.e., the contrast between the patches and the matrix was the largest in the more closed grasslands.

Visual consequent stimulus complexity affects performance in audiovisual associative learning.

In associative learning (AL), cues and/or outcome events are coupled together. AL is typically tested in visual learning paradigms. Recently, our group developed various AL tests based on the Rutgers Acquired Equivalence Test (RAET), both visual and audiovisual, keeping the structure and logic of RAET but with different stimuli. In this study, 55 volunteers were tested in two of our audiovisual tests, SoundFace (SF) and SoundPolygon (SP). The antecedent stimuli in both tests are sounds, and the consequent stimuli are images. The consequents in SF are cartoon faces, while in SP, they are simple geometric shapes. The aim was to test how the complexity of the applied consequent stimuli influences performance regarding the various aspects of learning the tests assess (stimulus pair learning, retrieval, and generalization of the previously learned associations to new but predictable stimulus pairs). In SP, behavioral performance was significantly poorer than in SF, and the reaction times were significantly longer, for all phases of the test. The results suggest that audiovisual associative learning is significantly influenced by the complexity of the consequent stimuli.

Co-seeding grasses and forbs supports restoration of species-rich grasslands and improves weed control in ex-arable land.

Sowing is widely used for the restoration of species-rich grasslands but still there are knowledge gaps regarding the most suitable application of different seed mixtures. We tested the effect of seed mixtures application timing on the establishment of sown forbs and weed control. 36 experimental plots with nine sowing treatments were established in an abandoned cropland in Hungary. Grass-seeds, diverse forb seed mixture and the combination of the two were applied: diverse forb mixture was sown simultaneously or 1, 2 or 3 years after grass sowing, in plots sown previously with grass or in empty plots (fallows). All sowing treatments supported the rapid establishment of the sown species in large cover and hampered weed encroachment. Forbs performed better when sown into fallows than in grass-matrix and forbs establishment was worse in older fallows than in younger ones. Grasses expressed a strong priority effect, especially when forbs were sown at least two years later than grasses. We also investigated the relation between seed germinability, weather parameters and establishment success. Germination rate in the greenhouse could not predict the establishment success of forbs in the field and showed great differences between years, hence we recommend sowing target forbs in multiple years.

Investigation of Surface Properties and Free Volumes of Chitosan-Based Buccal Mucoadhesive Drug Delivery Films Containing Ascorbic Acid.

Nowadays, the buccal administration of mucoadhesive films is very promising. Our aim was to prepare ascorbic acid-containing chitosan films to study the properties and structures important for applicability and optimize the composition. During the formulation of mucoadhesive films, chitosan as the polymer basis of the film was used. Ascorbic acid, which provided the acidic pH, was used in different concentrations (2-5%). The films were formulated by the solvent casting method. The properties of films important for applicability were investigated, such as physical parameters, mucoadhesive force, surface free energy, and breaking strength. The fine structure of the films was analyzed by atomic force microscopy, and the free volume was analyzed by PALS, which can be important for drug release kinetics and the location of the drug in the film. The applicability of the optimized composition was also tested with two different types of active ingredients. The structure of the films was also analyzed by XRPD and FTIR. Ascorbic acid can be used well in chitosan films, where it can function as a permeation enhancer when reacting to chitosan, it is biodegradable, and can be applied in 2% of our studies.

The Influence of Stimulus Complexity on the Effectiveness of Visual Associative Learning.

Visually guided equivalence learning is a special type of associative learning, which can be evaluated using the Rutgers Acquired Equivalence Test (RAET) among other tests. RAET applies complex stimuli (faces and colored fish) between which the test subjects build associations. The complexity of these stimuli offers the test subject several clues that might ease association learning. To reduce the number of such clues, we developed an equivalence learning test (Polygon), which is structured as RAET but uses simple grayscale geometric shapes instead of faces and colored fish. In this study, we compared the psychophysical performances of the same healthy volunteers in both RAET and Polygon test. Equivalence learning, which is a basal ganglia-associated form of learning, appears to be strongly influenced by the complexity of the visual stimuli. The simple geometric shapes were associated with poor performance as compared to faces and fish. However, the difference in stimulus complexity did not affect performance in the retrieval and transfer parts of the test phase, which are assumed to be mediated by the hippocampi.

Vertical distribution of soil seed bank and the ecological importance of deeply buried seeds in alkaline grasslands.

Background: Soil seed banks play a central role in vegetation dynamics and may be an important source of ecological restoration. However, the vast majority of seed bank studies examined only the uppermost soil layers (0-10 cm); hence, our knowledge on the depth distribution of seed bank and the ecological significance of deeply buried seeds is limited. The aim of our study was to examine the fine-scale vertical distribution of soil seed bank to a depth of 80 cm, which is one of the largest studied depth gradients so far. Our model systems were alkaline grasslands in East-Hungary, characterised by harsh environmental conditions, due to Solonetz soil reference group with Vertic horizon. We asked the following questions: (1) How do the seedling density and species richness of soil seed bank change along a vertical gradient and to what depth can germinable seeds be detected? (2) What is the relationship between the depth distribution of the germinable seeds and the species traits? Methods: In each of the five study sites, four soil cores (4 cm diameter) of 80 cm depth were collected with an auger for soil seed bank analysis. Each sample was divided into sixteen 5-cm segments by depth (320 segments in total). Samples were concentrated by washing over sieves and then germinated in an unheated greenhouse. Soil penetration resistance was measured in situ next to each core location (0-80 cm depth, 1-cm resolution). We tested the number and species richness of seedlings observed in the soil segments (N = 320), using negative binomial generalized linear regression models, in which sampling layer and penetration resistance were the predictor variables. We ran the models for morphological groups (graminoids/forbs), ecological groups (grassland species/weeds) and life-form categories (short-lived/perennial). We also tested whether seed shape index, seed mass, water requirement or salt tolerance of the species influence the vertical distribution of their seed bank. Results: Germinable seed density and species richness in the seed bank decreased with increasing soil depth and penetration resistance. However, we detected nine germinable seeds of six species even in the deepest soil layer. Forbs, grassland species and short-lived species occurred in large abundance in deep layers, from where graminoids, weeds and perennial species were missing. Round-shaped seeds were more abundant in deeper soil layers compared to elongated ones, but seed mass and ecological indicator values did not influence the vertical seed bank distribution. Our research draws attention to the potential ecological importance of the deeply buried seeds that may be a source of recovery after severe disturbance. As Vertisols cover 335 million hectares worldwide, these findings can be relevant for many regions and ecosystems globally. We highlight the need for similar studies in other soil and habitat types to test whether the presence of deep buried seeds is specific to soils with Vertic characteristics.

Linking environmental heterogeneity and plant diversity: The ecological role of small natural features in homogeneous landscapes.

Small natural features (SNFs), such as road verges, midfield islets, rocky outcrops and ancient burial mounds, provide safe havens for species of natural habitats in human-modified landscapes; therefore, their great ecological importance is in contrast to their small size. SNFs often have a high topographical heterogeneity and abiotic conditions, which differ from their surroundings; therefore, they provide a unique opportunity for establishing links between environmental heterogeneity (EH) and biodiversity. However, no study has so far investigated the EH components of topographically heterogeneous SNFs in a comprehensive framework, by linking environmental and biotic parameters. To fill this knowledge gap, we evaluated the EH components and their effect on biodiversity on ancient mounds covered by semi-natural grasslands in the Pannonian (Hungary) and Continental (Bulgaria) biogeographical regions. We designated 16 study sites, each containing a few-metre-high mounds with five microsites (top, north-, east-, south- and west-facing slopes) and a nearby plain grassland. At each microsite, we measured soil moisture, soil chemical properties, solar radiation and microclimate; and recorded the cover of vascular plants in a total of 480 plots. On the mounds, topographical heterogeneity was associated with sharp differences in microclimate and soil properties. Besides the contrast between mild north-facing and harsh south-facing slopes, east- and west-facing slopes also sustained unique microsites characterised by dynamic diurnal changes in air temperature and vapour pressure deficit. Various combinations of the EH components resulted in unique plant species compositions within the microsites, and supported the co-occurrence of species typical of contrasting habitat types, even within a couple of metres. By combining high-resolution measurements of abiotic factors with fine-scale vegetation sampling, our study provides evidence that widespread SNFs with complex topography harbour several grassland-specialist plant species and introduce a high level of EH to otherwise homogeneous plain landscapes, which cover one third of the global land area.

Preparation and investigation of core-shell nanoparticles containing human interferon-α.

Sustained release of active interferon-α (IFN-α) has been achieved from core-shell nanoparticles (NPs) prepared by aqueous precipitation of IFN-α-enriched human serum albumin (HSA-IFN-α) and layer-by-layer (L-b-L) by coating of the IFN-α NPs with poly(sodium-4-styrene) sulphonate (PSS) and chitosan (Chit). The concentration and the pH of HSA solution were optimized during the development of this method. Dynamic light scattering (DLS), zeta-potential, thermal analysis (differential scanning calorimetry (DSC) and termogravimetry (TG)), X-ray diffraction (XRD), IFN-α activity and morphology (transmission electron microscope (TEM)) studies were used to control the preparation and analyse the products. The dissolution kinetics of NPs was measured in vitro over 7 days in Hanson dissolution tester with Millex membrane. In vivo studies in Pannon white rabbit detected steady IFN-α plasma level for 10 days after subcutaneous injection administration of the HSA-IFN-α NPs. The IFN-α plasma concentration was detected by using the enzyme-linked immunosorbent assay (ELISA) method. In the present paper we discuss the preparation method, the optimization steps and the results of in vitro and in vivo release studies. It was established that 76.13% HSA-IFN-α are encapsulated in the core-shell NPs.

Design and characterization of chitosan/citrate films as carrier for oral macromolecule delivery.

The oral delivery of biopharmaceuticals requires the including of absorption enhancer, protease inhibitor and a suitable carrier system. The aim of the present work was to formulate and characterize chitosan solutions/films incorporating citric acid (CA) as potential excipient in comparison to the well-known acetic acid (AA)-based films as a reference. Films were made by the solvent casting method with/without glycerol (G), propylene glycol (PG) and polyethylene glycol (PEG-400) as plasticizers. The minimum film forming temperature (MFFT) of the prepared solutions, film thickness, hardness/deformation, mucoadhesivity, moisture content, FT-IR spectra and surface free energy (SFE) were investigated. Chitosan has been reported as a safe and effective paracellular absorption enhancer for hydrophilic macromolecules, therefore there would be more rationale for incorporating CA as a solubility enhancer, a permeation enhancer and an enzyme inhibitor. CA shows good cross-linking, an ideal plasticizing property and increases both tensile strength and mucoadhesivity, thus its incorporation simplifies the formulation while improving effectiveness. We concluded that CA (3.5, 4 and 5 w/v %)-based chitosan solution could be used as a novel coating/subcoating polymer for oral macromolecule delivery, or as oral mucoadhesive films.