Rapid quantification models for assessing melamine adulteration in sport nutrition supplements via benchtop and portable NIRS instruments.

Sport nutrition supplements (SNS) are vulnerable to adulteration with melamine, artificially augmenting their protein content as determined by conventional assay methodologies. Vibrational spectroscopy techniques are suitable for the detection of adulteration because they allow rapid analysis, require minimal sample preparation, and can perform numerous analyses in a short time. The aim of this study was to develop rapid quantification models for the determination of melamine adulteration in a variety of SNS matrices using NIRS (near-infrared spectroscopy) in combination with multivariate data processing. Moreover, a comparison of benchtop and portable NIR instruments was carried out. Employing a stepwise approach involving OPLS-DA and PLS analysis, matrix discrimination and prediction ability were investigated. The benchtop instrument effectively discriminated among matrices (R2Y = 0.964, Q2 = 0.933), while the portable device, although showing a slightly altered pattern, maintained favorable discrimination capability (R2Y = 0.966, Q2 = 0.931). The quantitative PLS models for each SNS matrix exhibited comparable statistical indicators for both instruments with reasonable errors for melamine content estimation and prediction (RMSEE: 0.3-2.4 %, RMSEP: 0.98-2.99 %). Higher estimation and prediction errors were observed for protein-containing samples in both acquisition modes, probably due to the tendency of protein agglomeration and adhesion to different surfaces, which affects the homogeneity of the powder. Despite data loss due to the narrower spectral range and lower resolution of the portable instrument, all models were found to be suitable for predicting melamine content in sport nutrition supplements.

Development of novel portable NIR spectroscopy process analytical technology (PAT) tool for monitoring the transition of ibuprofen to ibuprofen sodium during wet granulation process.

The aim of this research was to develop a process analytical technology (PAT) tool for monitoring the transformation of the active ingredient ibuprofen into the fast-dissolving salt ibuprofen sodium during the wet granulation process. Two near-infrared (NIR) spectrophotometers, portable and benchtop spectrophotometer, were compared. During the analysis with the built models, both demonstrated comparable accuracy and precision (R2X = 0.995, R2Y = 0.927, Q2 = 0.995, and R2X = 0.990, R2Y = 0.948, Q2 = 0.992, respectively). Considering the applicability, a model based on the portable NIR spectroscopic data was chosen for further development and application as a PAT tool for monitoring different steps during the wet granulation process. The evaluation of the model's predictive capability involved analyzing laboratory trial batches with varying amounts of sodium carbonate, resulting in different concentrations of ibuprofen sodium at the end of the wet granulation process. Subsequently, tablets were manufactured from each trial batch, followed by dissolution analysis. The dissolution rate assays were in good agreement with the NIR-predicted concentrations of ibuprofen sodium at the end of the wet granulation process. Based on the results, the proposed model provides an excellent tool to monitor the ibuprofen acid-salt transformation, to determine the end-point of the reaction, and to efficiently control the wet granulation process.

Solid-State Phase Transformation of Monohydrate and Anhydrous Form II of Sitagliptin Phosphate into a Novel Anhydrous Form IV - Solvent-Driven, Temperature-Induced and Stress Testings.

The solid form landscape of sitagliptin phosphate was systematically evaluated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and X-ray powder diffraction (XRPD), supported by a plethora of auxiliary analytical techniques. The preformulation experiments resulted in the transition of sitagliptin phosphate monohydrate into a new anhydrous form (designated as form IV), obtained after recrystallization from absolute ethanol. The anhydrous form IV remained stable under stressed conditions (1 month at 25 °C/60 %RH and 40 °C/75 %RH). On the other hand, thermal heating (dehydration) of sitagliptin phosphate monohydrate resulted in conversion into another anhydrous form II. Form II was found to be metastable, because after melting, under exposure at 40 °C/75 %RH for 1 month, or when dissolved in absolute ethanol converted to the stable anhydrous form IV of sitagliptin phosphate. A monotropic relationship was found between both studied anhydrous forms. Intrinsic dissolution tests revealed differences in the dissolution rates between the monohydrate and the anhydrous forms of sitagliptin phosphate. This research corrects the record with an accurate chemical composition of the anhydrous form IV of sitagliptin phosphate that was previously regarded as a hemiethanolate. In addition, the crystal structure of anhydrous form II of sitagliptin phosphate has been solved and reported for the first time.

Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery.

Lipid nano-systems were prepared and characterized in a series of well-established in vitro tests that could assess their interactions with the hCMEC/D3 and SH-SY5Y cell lines as a model for the blood-brain barrier and neuronal function, accordingly. The prepared formulations of nanoliposomes and nanostructured lipid carriers were characterized by z-average diameters of ~120 nm and ~105 nm, respectively, following a unimodal particle size distribution (PDI < 0.3) and negative Z-potential (-24.30 mV to -31.20 mV). Stability studies implied that the nano-systems were stable in a physiologically relevant medium as well as human plasma, except nanoliposomes containing poloxamer on their surface, where there was an increase in particle size of ~26%. The presence of stealth polymer tends to decrease the amount of adsorbed proteins onto a particle's surface, according to protein adsorption studies. Both formulations of nanoliposomes were characterized by a low cytotoxicity, while their cell viability was reduced when incubated with the highest concentration (100 µg/mL) of nanostructured lipid formulations, which could have been associated with the consumption of cellular energy, thus resulting in a reduction in metabolic active cells. The uptake of all the nano-systems in the hCMEC/D3 and SH-SY5Y cell lines was successful, most likely following ATP-dependent internalization, as well as transport via passive diffusion.

A Unique Mechanochemical Redox Reaction Yielding Nanostructured Double Perovskite Sr2FeMoO6 With an Extraordinarily High Degree of Anti-Site Disorder.

Strontium ferromolybdate, Sr2FeMoO6, is an important member of the family of double perovskites with the possible technological applications in the field of spintronics and solid oxide fuel cells. Its preparation via a multi-step ceramic route or various wet chemistry-based routes is notoriously difficult. The present work demonstrates that Sr2FeMoO6 can be mechanosynthesized at ambient temperature in air directly from its precursors (SrO, α-Fe, MoO3) in the form of nanostructured powders, without the need for solvents and/or calcination under controlled oxygen fugacity. The mechanically induced evolution of the Sr2FeMoO6 phase and the far-from-equilibrium structural state of the reaction product are systematically monitored with XRD and a variety of spectroscopic techniques including Raman spectroscopy, 57Fe Mössbauer spectroscopy, and X-ray photoelectron spectroscopy. The unique extensive oxidation of iron species (Fe0 → Fe3+) with simultaneous reduction of Mo cations (Mo6+ → Mo5+), occuring during the mechanosynthesis of Sr2FeMoO6, is attributed to the mechanically triggered formation of tiny metallic iron nanoparticles in superparamagnetic state with a large reaction surface and a high oxidation affinity, whose steady presence in the reaction mixture of the milled educts initiates/promotes the swift redox reaction. High-resolution transmission electron microscopy observations reveal that the mechanosynthesized Sr2FeMoO6, even after its moderate thermal treatment at 923 K for 30 min in air, exhibits the nanostructured nature with the average particle size of 21(4) nm. At the short-range scale, the nanostructure of the as-prepared Sr2FeMoO6 is characterized by both, the strongly distorted geometry of the constituent FeO6 octahedra and the extraordinarily high degree of anti-site disorder. The degree of anti-site disorder ASD = 0.5, derived independently from the present experimental XRD, Mössbauer, and SQUID magnetization data, corresponds to the completely random distribution of Fe3+ and Mo5+ cations over the sites of octahedral coordination provided by the double perovskite structure. Moreover, the fully anti-site disordered Sr2FeMoO6 nanoparticles exhibit superparamagnetism with the blocking temperature T B = 240 K and the deteriorated effective magnetic moment µ = 0.055 µ B per formula unit.

Electrospun PEO/rGO Scaffolds: The Influence of the Concentration of rGO on Overall Properties and Cytotoxicity.

Reduced graphene oxide (rGO) is one of the graphene derivatives that can be employed to engineer bioactive and/or electroactive scaffolds. However, the influence of its low and especially high concentrations on scaffolds' overall properties and cytotoxicity has yet to be explored. In this study, polyethylene oxide (PEO)-based scaffolds containing from 0.1 to 20 wt% rGO were obtained by electrospinning. Morphological, thermal and electrical properties of the scaffolds were characterized by SEM, Raman spectroscopy, XRD, DSC and electrical measurements. The diameter of the fibers decreased from 0.52 to 0.19 µm as the concentration of rGO increased from 0.1 wt% to 20 wt%. The presence of rGO above the percolation threshold (5.7 wt%) resulted in a significantly reduced electrical resistivity of the scaffolds. XRD and Raman analysis revealed delamination of the graphene layers (interlayer spacing increased from 0.36 nm to 0.40-0.41 nm), and exfoliation of rGO was detected for the samples with an rGO concentration lower than 1 wt%. In addition, an evident trend of increasing cell viability as a function of the rGO concentration was evidenced. The obtained results can serve as further guidance for the judicious selection of the rGO content incorporated into the PEO matrix for constructing electroactive scaffolds.

Design and evaluation of nanostructured lipid carriers loaded with Salvia officinalis extract for Alzheimer's disease treatment.

Considering the potential of Salvia officinalis in prevention and treatment of Alzheimer's disease (AD), as well as the ability of nanostructured lipid carriers (NLC) to successfully deliver drug molecules across blood-brain barrier (BBB), the objective of this study was design, development, optimization and characterization of freeze-dried salvia officinalis extract (FSE) loaded NLC intended for intranasal administration. NLC were prepared by solvent evaporation method and the optimization was carried out using central composite design (CCD) of experiments. Further, the optimized formulation (NLCo) was coated either with chitosan (NLCc) or poloxamer (NLCp). Surface characterization of the particles demonstrated a spherical shape with smooth exterior. Particle size of optimal formulations after 0.45 µm pore size filtration ranged from 127 ± 0.68 nm to 140 ± 0.74 nm. The zeta potential was -25.6 ± 0.404 mV; 22.4 ± 1.106 mV and - 6.74 ± 0.609 mV for NLCo, NLCc, and NLCp, respectively. Differential scanning calorimetry (DSC) confirmed the formation of NLC whereas Fourier-transform infrared spectroscopy confirmed the FSE encapsulation into particles. All formulations showcased relatively high drug loading (>86.74 mcg FSE/mg solid lipid) and were characterized by prolonged and controlled release that followed Peppas-Sahlin in vitro release kinetic model. Protein adsorption studies revealed the lowest adsorption of the proteins onto NLCp (43.53 ± 0.07%) and highest protein adsorption onto NLCc (55.97 ± 0.75%) surface. The modified ORAC assay demonstrated higher antioxidative activity for NLCo (95.31 ± 1.86%) and NLCc (97.76 ± 4.00%) as compared to FSE (90.30 ± 1.53%). Results obtained from cell cultures tests pointed to the potential of prepared NLCs for FSE brain targeting and controlled release.

Design of ophthalmic micelles loaded with diclofenac sodium: effect of chitosan and temperature on the block-copolymer micellization behaviour.

Diclofenac sodium 0.1% is a commonly used NSAID with well-documented clinical efficacy in reducing postoperative inflammation; however, its corneal tolerability and ophthalmic tissue bioavailability require further improvement. Advanced micellar delivery systems composed of block-copolymers and chitosan showing fine balance between the mucoadhesion and mucus permeation, capable to slip through the mucus barrier and adhere to the epithelial ocular surface, may be used to tackle both challenges. The aggregation behaviour of the block-copolymers in the presence of different additives will dramatically influence the quality attributes like particle size, particle size distribution, drug-polymer interaction, zeta potential, drug incorporation, important for the delicate balance among mucoadhesion and permeation, as well as safety and efficacy of the ophthalmic micelles. Therefore, quality by design approach and D-optimal experimental design model were used to create a pool of useful data for the influence of chitosan and the formulation factors on the block copolymer's aggregation behaviour during the development and optimization of Diclofenac loaded Chitosan/Lutrol F127 or F68 micelles. Particle size, polydispersity index, dissolution rate, FTIR and DSC studies, NMR spectroscopy, cytotoxicity, mucoadhesivity, mucus permeation studies, and bioadhesivity were assessed as critical quality attributes. FTIR and DSC studies pointed to the chaotropic effect of chitosan during the micelle aggregation. Mainly, Pluronic F68 micellization behaviour was more dramatically affected by the presence of chitosan, and self-aggregation into larger micelles with high polydispersity index was favoured at higher chitosan concentration. The optimized formulation with highest potential for ophthalmic delivery of diclofenac sodium, good cytotoxicity profile, delicate balance of the mucoadhesivity, and mucus permeation was in the design space of Chitosan/Lutrol F127 micelles.

A unique approach for in-situ monitoring of the THCA decarboxylation reaction in solid state.

The decarboxylation of Δ9-tetrahydrocannabinolic acid (THCA) plays pivotal role in the potency of medical cannabis and its extracts. Our present work aims to draw attention to mid-infrared (MIR) spectroscopy to in-situ monitor and decipher the THCA decarboxylation reaction in the solid state. The initial TG/DTG curves of THCA, for a first time, outlined the solid-solid decarboxylation dynamics, defined the endpoint of the process and the temperature of the maximal conversion rate, which aided in the design of the further IR experiment. Temperature controlled IR spectroscopy experiments were performed on both THCA standard and cannabis flower by providing detailed band assignment and conducting spectra-structure correlations, based on the concept of functional groups vibrations. Moreover, a multivariate statistical analysis was employed to address the spectral regions of utmost importance for the THCA â†’ THC interconversion process. The principal component analysis model was reduced to two PCs, where PC1 explained 94.76% and 98.21% of the total spectral variations in the THCA standard and in the plant sample, respectively. The PC1 plot score of the THCA standard, as a function of the temperature, neatly complemented to the TG/DTG curves and enabled determination of rate constants for the decarboxylation reaction undertaken on several selected temperatures. The predictive capability of MIR was further demonstrated with PLS (R2X = 0.99, R2Y = 0.994 and Q2 = 0.992) using thermally treated flower samples that covered broad range of THCA/THC content. Consequently, a progress in elucidation of kinetic models of THCA decarboxylation in terms of fitting the experimental data for both, solid state standard substance and a plant flower, was achieved. The results open the horizon to promote an appropriate process analytical technology (PAT) in the outgrowing medical cannabis industry.

A Novel Method for Rapid Particle Size Analysis of Ibuprofen Using Near-infrared Spectroscopy.

Particle size distribution (PSD) is often considered as critical material attribute for active pharmaceutical ingredients (APIs), and the need for regular evaluation stands as an important quality control parameter in the pharmaceutical industry. Near-infrared (NIR) spectroscopy, used routinely for API identification, was introduced as analytical tool for simultaneous determination of particle size of ibuprofen. The demonstrated potential was highlighted by the development of rapid, robust, and noninvasive method coupled with multivariate data analysis (MVA), which can be easily transferred in QC laboratories for routine analysis. Principal component analysis (PCA) and partial least squares (PLS) regression analyses were performed on a calibration set of 61 ibuprofen samples, which differed in their median particle size Dv(50). The score scatterplots revealed evident clustering of ibuprofen samples according to their particle size, as well as occurrence of a distinctive outlying group of ibuprofen samples originating from one manufacturer. Further testing by means of mid-infrared spectroscopy, X-ray powder diffraction, and particle morphology analysis pinpointed particle morphology being responsible for the observed outlying group. Consequently, PLS class modeling based on particle morphology was introduced, which delivered two separate PLS regression models: one for blade-like ibuprofen crystals and another for irregular plate-like ibuprofen crystals. The former regression model exhibited high correlation coefficients and satisfactory predictive power (R2X = 0.999, R2Y = 0.917, Q2 = 0.901), whereas the latter demonstrated lower statistical indicators (R2X = 0.99, R2Y = 0.72, Q2 = 0.55). Additionally, the study underlines the importance of particle shape evaluation and sample classification according to particle morphology similarity prior to building NIRS-based regression models for PSD determination.

Mid-infrared spectroscopy as process analytical technology tool for estimation of THC and CBD content in Cannabis flowers and extracts.

Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most notable Cannabis components with pharmacological activity and their content in the plant flowers and extracts are considered as critical quality parameters. The new Medical Cannabis industry needs to adopt the quality standards of the pharmaceutical industry, however, the variability of phytocannabinoids content in the plant material often exerts an issue in the inconsistency of the finished product quality parameters. Sampling problems and sample representativeness is a major limitation in the end-point testing, particularly when the expected variation of the product quality parameters is high. Therefore, there is an obvious need for the introduction of Process Analytical Technology (PAT) for continuous monitoring of the critical quality parameters throughout the production processes. Infrared spectroscopy is a promising analytical technique that is consistent with the PAT requirements and its implementation depends on the advances in instrumentation and chemometrics that will facilitate the qualitative and quantitative aspects of the technique. Our present work aims in highlighting the potential of mid-infrared (MIR) spectroscopy as PAT in the quantification of the main phytocannabinoids (THC and CBD), considered as critical quality/material parameters in the production of Cannabis plant and extract. A detailed assignment of the bands related to the molecules of interest (THC, CBD) was performed, the spectral features of the decarboxylation of native flowers were identified, and the specified bands for the acid forms (THCA, CBDA) were assigned and thoroughly explained. Further, multivariate models were constructed for the prediction of both THC and CBD content in extract and flower samples from various origins, and their prediction ability was tested on a separate sample set. Savitskzy-Golay smoothing and the second derivative of the native MIR spectra (1800-400 cm-1 region) resulted in best-fit parameters. The PLS models presented satisfactory R2Y and RMSEP of 0.95 and 3.79% for THC, 0.99 and 1.44% for CBD in the Cannabis extract samples, respectively. Similar statistical indicators were noted for the Partial least-squares (PLS) models for THC and CBD prediction of decarboxylated Cannabis flowers (R2Y and RMSEP were 0.99 and 2.32% for THC, 0.99 and 1.33% for CBD respectively). The VIP plots of all models demonstrated that the THC and CBD distinctive band regions bared the highest importance for predicting the content of the molecules of interest in the respected PLS models. The complexity of the sample (plant tissue or plant extract), the variability of the samples regarding their origin and horticultural maturity, as well as the non-uniformity of the plant material and the flower-ATR crystal contact (in the case of Cannabis flowers) were governing the accuracy descriptors. Taking into account the presented results, ATR-MIR should be considered as a promising PAT tool for THC and CBD content estimation, in terms of critical material and quality parameters for Cannabis flowers and extracts.

Solid-state interaction of ibuprofen with magnesium stearate and product characterization thereof.

Solid-state compatibility of API with excipients is essential step in the preformulation stage of early development of new finished dosage form. Thermal analysis and vibrational spectroscopy are complementary techniques that play a pivotal role to assess the solid-state compatibility of API with excipients. Their coupling and combination with multivariate analysis, provide valuable quantitative aspect to reveal the potential interactions. The impetus of this work was aimed to fully elucidate the solid-state compatibility of ibuprofen and magnesium stearate in binary mixtures comprising pharmaceutically acceptable amounts of magnesium stearate (0.25-5% w/w). Binary mixtures were analyzed before and after exposure at strictly controlled stress conditions (25 °C/60% relative humidity and 40 °C/75% relative humidity). Interaction between ibuprofen and magnesium stearate was unambiguously confirmed. The product of their interaction was synthetized separately, characterized by means of FTIR spectroscopy, DSC, TG/DTG and XRPD for the first time and identified as diibuprofen magnesium. The induced solid-state pseudopolymorphic transition of this product to diibuprofen magnesium tetrahydrate was also studied and discussed.

A Comparative Approach to Screen the Capability of Raman and Infrared (Mid- and Near-) Spectroscopy for Quantification of Low-Active Pharmaceutical Ingredient Content Solid Dosage Forms: The Case of Alprazolam.

Content uniformity is a critical attribute for potent and low-dosage formulations of active pharmaceutical ingredient (API) that, in addition to the formulation parameters, plays pivotal role during pharmaceutical development and production. However, when API content is low, implementing a vibrational spectroscopic analytical tool to monitor the content and blend uniformity remains a challenging task. The aim of this study was to showcase the potentials of mid-infrared (MIR), near-infrared (NIR), and Raman spectroscopy for quantitative analysis of alprazolam (ALZ) in a low-content powder blends with lactose, which is used as a common diluent for tablets produced by direct compression. The offered approach might be further scaled up and exploited for potential application in the process analytical technology (PAT). Partial least square and orthogonal PLS (OPLS) methodologies were employed to build the calibration models from raw and processed spectral data (standard normal variate, first and second derivatives). The models were further compared regarding their main statistical indicators: correlation coefficients, predictivity, root mean square error of estimation (RMSEE), and root mean square error of cross-validation (RMSEEcv). All statistical models presented high regression and predictivity coefficients. The RMSEEcv for the optimal models was 1.118, 0.08, and 0.059% for MIR, NIR, and Raman spectroscopy, respectively. The scarce information content extracted from the ALZ NIR spectra and the major band overlapping with those from lactose monohydrate was the main culprit of poor accuracy in the NIR model, whereas the subsampling instrumental setup (resulting in a non-representative spectral acquisition of the sample) was regarded as a main limitation for the MIR-based calibration model. The OPLS models of the Raman spectra of the powder blends manifested favorable statistical indicators for the accuracy of the calibration model, probably due to the distinctive ALZ Raman pattern resulting in the largest number of predictive spectral points that were used for the mathematical modeling. Furthermore, the Raman scattering calibration model was optimized in narrower scanning range (1700-700 cm-1) and its prediction power was evaluated (root mean square error of prediction, RMSEP = 0.03%). Thus, the Raman spectroscopy presented the most favorable statistical indicators in this comparative study and therefore should be further considered as a PAT for the quantitative determination of ALZ in low-content powder blends.

Effects of the presence of probiotic bacteria in the aging medium on the surface roughness and chemical composition of two dental alloys.

The aims of this study were: (a) to determine if the presence of probiotic bacteria in an aging medium, that is, artificial saliva in this study, has relevant effects on the surface roughness and the chemical composition of two main alloys used in dentistry (NiTi and stainless steel [SS]) and (b) in the case of NiTi, if these effects are influenced by the coating of the alloy (rhodium and titanium nitride). Atomic force microscopy and Raman spectroscopy were used to study the surface morphology and identify metal oxides formed on the surface of the alloys. Experiments demonstrated that the probiotic bacteria Lactobacillus reuteri can induce processes that alter some features of the surface such as roughness and chemical composition. The effect is dependent on the type of alloy and coating. The bacteria increased roughness in the case of uncoated NiTi more than saliva alone (pH = 4.8). Probiotic bacteria tend to decrease the corrosive influence of saliva on NiTi when the alloy is coated with rhodium or titanium nitride and this effect was also evidenced on SS. Raman spectroscopy confirmed that only SS samples are prone to oxidation processes, predominantly associated with exposure to saliva rather than probiotic bacteria.

Preparation, Optimization, In vitro Evaluation and Ex vivo Permeation Studies of Finasteride loaded gel Formulations Prepared by using Response Surface Methodology.

OBJECTIVES: The aim of the present explorative study was to prepare and optimize finasteride loaded topical gel formulations by using three factor [propylene glycol (PG), Tween® 80, and sodium lauryl sulphate (SLS)], five level central composite design. RESULTS: Optimized finasteride topical gel formulation (F4), containing PG, Tween® 80, and SLS in a concentration of 0.8 mg, 0.4 mg and 0.2 mg, respectively, showed 6-fold higher values of cumulative drug release, flux, partition coefficient, input rate, lag time, and diffusion coefficient, when compared to control formulation without permeation enhancer. CONCLUSION: Finally, it can be concluded that finasteride permeation was enhanced by PG, tween® 80 and SLS individually, while in combination only PG along with tween® 80 had synergistic and more pronounced effect on flux, permeability coefficient and input rate while antagonistic effect on lag time and diffusion coefficient was observed.

Development and experimental design of a novel controlled-release matrix tablet formulation for indapamide hemihydrate.

CONTEXT: Development, experimental design and in vitro in vivo correlation (IVIVC) of controlled-release matrix formulation. OBJECTIVE: Development of novel oral controlled delivery system for indapamide hemihydrate, optimization of the formulation by experimental design and evaluation regarding IVIVC on a pilot scale batch as a confirmation of a well-established formulation. MATERIALS AND METHODS: In vitro dissolution profiles of controlled-release tablets of indapamide hemihydrate from four different matrices had been evaluated in comparison to the originator's product Natrilix (Servier) as a direction for further development and optimization of a hydroxyethylcellulose-based matrix controlled-release formulation. A central composite factorial design had been applied for the optimization of a chosen controlled-release tablet formulation. RESULTS: The controlled-release tablets with appropriate physical and technological properties had been obtained with a matrix: binder concentration variations in the range: 20-40w/w% for the matrix and 1-3w/w% for the binder. The experimental design had defined the design space for the formulation and was prerequisite for extraction of a particular formulation that would be a subject for transfer on pilot scale and IVIV correlation. CONCLUSIONS: The release model of the optimized formulation has shown best fit to the zero order kinetics depicted with the Hixson-Crowell erosion-dependent mechanism of release. Level A correlation was obtained.

Theoretical and experimental study of the vibrational spectra of (para)symplesite and hörnesite.

Arsenate water-bearing minerals, hörnesite (Alsar, Macedonia) and symplesite (Laubach, Germany), were studied by vibrational (IR and Raman) spectroscopy and X-ray powder diffraction. The observed vibrational spectra in both the high (1100-600 cm(-1)) and low (600-450 cm(-1)) wavenumber regions of AsO4 and H2O vibrations could be used to discriminate the two studied minerals. Spectral differences are especially pronounced in the bending and stretching regions of the H2O vibrations in the IR spectra. The observed bands in IR and Raman spectra were tentatively assigned. To support the assignment, IR spectra were theoretically simulated. These calculations were performed using the crystal structure of parasymplesite (no structural information of symplesite has been published so far) and hörnesite using a 3D periodic plane-wave pseudopotential density functional theory approach applying various combinations of exchange-correlation functionals. In this article, we report on the first experimental study of the vibrational spectra of the very rare symplesite mineral.

Distribution of chemical elements in soils and stream sediments in the area of abandoned Sb-As-Tl Allchar mine, Republic of Macedonia.

The aim of this study was to investigate the distribution of some toxic elements in topsoil and subsoil, focusing on the identification of natural and anthropogenic element sources in the small region of rare As-Sb-Tl mineralization outcrop and abandoned mine Allchar known for the highest natural concentration of Tl in soil worldwide. The samples of soil and sediments after total digestion were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES). Factor analysis (FA) was used to identify and characterize element associations. Six associations of elements were determined by the method of multivariate statistics: Rb-Ta-K-Nb-Ga-Sn-Ba-Bi-Li-Be-(La-Eu)-Hf-Zr-Zn-In-Pd-Ag-Pt-Mg; Tl-As-Sb-Hg; Te-S-Ag-Pt-Al-Sc-(Gd-Lu)-Y; Fe-Cu-V-Ge-Co-In; Pd-Zr-Hf-W-Be and Ni-Mn-Co-Cr-Mg. The purpose of the assessment was to determine the nature and extent of potential contamination as well as to broadly assess possible impacts to human health and the environment. The results from the analysis of the collected samples in the vicinity of the mine revealed that As and Tl elements have the highest median values. Higher median values for Sb are obviously as a result of the past mining activities and as a result of area surface phenomena in the past.

On the hydrates of codeine phosphate: the remarkable influence of hydrogen bonding on the crystal size.

Codeine phosphate forms three hydrates and two anhydrates. The sesquihydrate and hemihydrate, which differ by one water molecule, are stable at room temperature. The influence of this molecule on the internal crystal structure and how it translates into the external crystal shape are reported.

Theoretical and experimental study of the vibrational spectra of sarkinite Mn2(AsO4)(OH) and adamite Zn2(AsO4)(OH).

The arsenate hydroxyl-bearing minerals sarkinite and adamite were studied with vibrational spectroscopic (IR and Raman) and quantum theoretical methods. The observed IR bands in the higher (1100-600 cm(-1)) and especially lower (600-450 cm(-1)) frequency region of AsO4 vibrations could clearly discriminate between the studied analogues. The differences between their crystal structures are much pronounced in both IR and Raman OH-stretching regions. Namely, a single strong band is found in the case of orthorhombic adamite compared to four weaker bands observed in corresponding IR and Raman spectral regions of monoclinic sarkinite. Essentially all bands in the experimental spectra, collected at both room and liquid nitrogen temperature, were tentatively assigned. To support the tentative assignment of bands in the vibrational spectra of the mentioned minerals, periodic pseudopotential plane wave density functional theory calculations were carried out. Geometry optimizations of the 3D periodic systems included both optimizations of the atomic positions within the unit cell and of the unit cell itself. In most cases, the assignments were either supported or implied by the obtained theoretical data. It is worth mentioning that this is the first experimental and theoretical study of the vibrational spectra of the very-rare sarkinite mineral.