The Influence of Contemporary Denture Base Fabrication Methods on Residual Monomer Content, Flexural Strength and Microhardness.

(1) Background: Digital technologies are available for denture base fabrication, but there is a lack of scientific data on the mechanical and chemical properties of the materials produced in this way. Therefore, the aim of this study was to investigate the residual monomer content, flexural strength and microhardness of denture base materials as well as correlations between investigated parameters. (2) Methods: Seven denture base materials were used: one conventional heat cured polymethyl methacrylate, one polyamide, three subtractive manufactured materials and two additive manufactured materials. High-performance liquid chromatography was used to determine residual monomer content and the test was carried out in accordance with the specification ISO No. 20795-1:2013. Flexural strength was also determined according to the specification ISO No. 20795-1:2013. The Vickers method was used to investigate microhardness. A one-way ANOVA with a Bonferroni post-hoc test was used for the statistical analysis. The Pearson correlation test was used for the correlation analysis. (3) Results: There was a statistically significant difference between the values of residual monomer content of the different denture base materials (p < 0.05). Anaxdent pink blank showed the highest value of 3.2% mass fraction, while Polident pink CAD-CAM showed the lowest value of 0.05% mass fraction. The difference between the flexural strength values of the different denture base materials was statistically significant (p < 0.05), with values ranging from 62.57 megapascals (MPa) to 103.33 MPa. The difference between the microhardness values for the different denture base materials was statistically significant (p < 0.05), and the values obtained ranged from 10.61 to 22.86 Vickers hardness number (VHN). A correlation was found between some results for the material properties investigated (p < 0.05). (4) Conclusions: The selection of contemporary digital denture base manufacturing techniques may affect residual monomer content, flexural strength and microhardness but is not the only criterion for achieving favourable properties.

Ternary Mixed Micelle Hexadecyltrimethylammonium Bromide-Dodecyltrimethylammonium Bromide-Sodium Deoxycholate: Gibbs Free Energy of Mixing and Excess Gibbs Energy of Mixing.

Pharmaceutical, food, and cosmetic formulations often contain binary or ternary surfactant mixtures with synergistic interactions amongst micellar building blocks. Here, a ternary mixture of the surfactants hexadecyltrimethylammonium bromide, dodecyltrimethylammonium bromide, and sodium deoxycholate is examined to see if the molar fractions of the surfactants in the ternary mixed micellar pseudophase are determined by the interaction coefficients between various pairs of the surfactants or by their propensity to self-associate. Critical micelle concentrations (CMC) of the analyzed ternary mixtures are determined experimentally (spectrofluorimetrically using pyrene as the probe molecule). Thermodynamic parameters of ternary mixtures are calculated from CMC values using the Regular Solution protocol. The tendency for monocomponent surfactants to self-associate (lower value of CMC) determines the molar fractions of surfactant in the mixed micelle if there is no issue with the packing of the micelle building units of the ternary mixed micelle. If a more hydrophobic surfactant is incorporated into the mixed micelle, the system (an aqueous solution of surfactants) is then the most thermodynamically stabilized.

Influence of Ageing on Optical, Mechanical, and Thermal Properties of Agricultural Films.

Plastic films utilized as greenhouse coverings play a vital role in safeguarding plantations from diverse weather conditions like sunlight, rain, hail, and wind. It is essential for these films to preserve their properties even after extended exposure to sunlight and water, while also maintaining transparency to support the unhindered growth of plants. The purpose of the study was to compare the properties of three types of plastic films: low density polyethylene diffuse film, low density polyethylene clear film, and ethylene tetrafluoroethylene film, before and after their ageing in weather test chamber with xenon-arc light in the presence of moisture. Two distinct types of PE films were chosen based on their suitability for specific regions in Croatia, whereas ETFE film was chosen as a potential new material that is gaining popularity across various industries, including agriculture. The properties investigated were tensile properties, transmittance by spectral analysis, and viscoelastic properties by dynamic mechanical analysis. Also, untreated films and the ones exposed to artificial ageing were compared by means of Fourier-transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. The administered tests revealed a certain level of property degradation due to ageing in all three films. However, none of the films showed a substantial level of deterioration, indicating their suitability as greenhouse coverings.

Optimization of Thermal Conductivity and Tensile Properties of High-Density Polyethylene by Addition of Expanded Graphite and Boron Nitride.

Due to its mechanical, rheological, and chemical properties, high-density polyethylene (HDPE) is commonly used as a material for producing the pipes for transport of various media. Low thermal conductivity (0.4 W/mK) narrows down the usage of HDPE in the heat exchanger systems. The main goal of the work is to reduce the vertical depth of the HDPE pipe buried in the borehole by increasing the thermal conductivity of the material. This property can be improved by adding certain additives to the pure HDPE matrix. Composites made of HDPE with metallic and non-metallic additives show increased thermal conductivity several times compared to the thermal conductivity of pure HDPE. Those additives affect the mechanical properties too, by enhancing or degrading them. In this research, the thermal conductivity and tensile properties of composite made of HDPE matrix and two types of additives, expanded graphite (EG) and boron nitride (BN), were tested. Micro-sized particles of EG and two different sizes of BN particles, micro and nano, were used to produce composite. The objective behind utilizing composite materials featuring dual additives is twofold: firstly, to enhance thermal properties, and secondly, to improve mechanical properties when compared with the pure HDPE. As anticipated, the thermal conductivity of the composites exhibited an eightfold rise in comparison to the pure HDPE. The tensile modulus experienced augmentation across all variations of additive ratios within the composites, albeit with a marginal reduction in tensile strength. This implies that the composite retains a value similar to pure HDPE in terms of tensile strength. Apart from the enhancement observed in all the aforementioned properties, the most significant downside of these composites pertains to their strain at yield, which experienced a reduction, declining from the initial 8.5% found in pure HDPE to a range spanning from 6.6% to 1.8%, dependent upon the specific additive ratios and the size of the BN particles.

Tensile Bond Strength between Different Denture Base Materials and Soft Denture Liners.

(1) Background: Various materials are available for CAD-CAM denture base fabrication, for both additive and subtractive manufacturing. However, little has been reported on bond strength to soft denture liners. Therefore, the aim of this study was to investigate tensile bond strength, comparing between different denture base materials and soft denture liners. (2) Methods: Seven different materials were used for denture base fabrication: one heat-polymerized polymethyl methacrylate, three materials for subtractive manufacturing, two materials for additive manufacturing and one polyamide. Two materials were used for soft denture lining: one silicone-based and one acrylate-based. The study was conducted according to the specification ISO No. 10139-2:2016, and the type of failure was determined. The Kruskal-Wallis test with Dunn's post hoc test was used to analyse the values of tensile bond strength, and Fisher's exact test was used to analyse the type of failure. p Values < 0.05 were considered statistically significant. (3) Results: The tensile bond strength values were not statistically significantly different combining all the materials used for denture base fabrication with the acrylate-based soft denture liner (p > 0.05), and the average values ranged between 0.19 and 0.25 Mpa. The tensile bond strength values of the different denture base materials and silicone-based denture liner were statistically significantly different (p < 0.05), and the average values ranged between 1.49 and 3.07 Mpa. The type of failure was predominantly adhesive between polyamide and both additive-manufactured denture base materials in combination with the acrylate-based soft liner (p < 0.05). (4) Conclusions: The use of digital technologies in denture base fabrication can have an influence on different tensile bond strength values for soft denture liners, with different types of failure when compared with heat-cured PMMA. Similar tensile bond strength values were found between the acrylate-based soft denture liner and denture base materials. Significant differences in tensile bond strength values were found between the silicone-based soft denture liner and denture base materials, where the additive-manufactured and polyamide denture base materials showed lower values than heat-cured PMMA and subtractive-manufactured denture base materials.

Plantaris tendon is valuable graft for the medial patellofemoral ligament reconstruction: A biomechanical study.

BACKGROUND: Medial patellofemoral ligament (MPFL) reconstruction is a standard treatment option for selected patients with patellar instability. Although frequently performed, the optimal graft source for the procedure has not yet been established. This study aimed to determine whether a two-strand plantaris tendon construct possesses the biomechanical properties needed to act as an MPFL reconstruction graft. METHODS: Thirty paired plantaris and gracilis tendons were harvested from 15 cadavers, mean age at death of 42.7 years. All specimens were frozen and maintained at -20 °C until biomechanical testing. Prior to mechanical testing, specimens were thawed at room temperature. The two-strand plantaris tendon and two-strand gracilis tendon constructs were created and secured in a uniaxial tensile testing machine in a triangular-shaped mode. Biomechanical properties for tensile testing to failure were determined using validated method. Results obtained were compared with the previously published data on native MPFL biomechanical properties. RESULTS: The mean maximal force was 220.3 ± 108.1 N and 448.1 ± 117 N for the two-strand plantaris tendon construct and two-strand gracilis tendon construct, respectively. Significant differences were observed between all biomechanical properties of two-strand plantaris tendon and two-strand gracilis tendon constructs. The mean maximal force of a two-strand plantaris tendon construct and a two-strand gracilis tendon construct were greater than the mean maximal force of the native MPFL reported in all previous studies. CONCLUSIONS: This study suggests that, due to its biomechanical properties, the two-strand plantaris tendon graft is suitable as a graft for MPFL reconstruction.

Influence of Atmospheric Conditions on Mechanical Properties of Polyamide with Different Content of Recycled Material in Selective Laser Sintering.

The price of material is an important factor when selecting the additive polymer procedure. In selective laser sintering (SLS), the price can be reduced by the recycling of material, i.e., with different shares of original and recycled material, as well as by the orientation of the product during manufacturing. Numerous tests warn that orientation in the direction of z axis should be as low as possible to reduce the total price of the product. The product also has to satisfy the influence of atmospheric conditions to which it is exposed during its lifetime, i.e., UV radiation and humid environment. UV light, with sun being its most common source, and average humidity in different parts of the world can be approximately from 20% to 90%, depending on time, day and geographic location. In this work, the test specimens have been made of original, mixed and 100% recycled material and then exposed to the influences of UV radiation and water absorption. After having been exposed to atmospheric conditions for a longer time, the mechanical properties of the polyamide products made by selective laser sintering were tested. The results show that exposure to UV radiation reduces tensile elongation at all ratios of recycled material and orientation of 70-90% except in the z direction, while in flexural deformation it is the other way around. The effect of water was observed only between the 7th-14th day of absorption with a decrease in strength until the deformation did not change.

Compressive Strength of Conventional Glass Ionomer Cement Modified with TiO2 Nano-Powder and Marine-Derived HAp Micro-Powder.

The aim of this research was to investigate the compressive strength (CS), breaking strength (BS), and compressive modulus (CM) of conventional glass ionomer cement (GIC) modified with TiO2 nano particles, marine-derived hydroxyapatite (md-HAp) microparticles (<45 µm), and a combination of TiO2 NP and md-HAp particles. The materials used in the study were conventional GIC Fuji IX GP Extra (GC Corporation, Tokyo, Japan), TiO2 powder P25 (Degussa, Essen, Germany), and HAp synthesized from cuttlefish bone and ground in a mortar to obtain md-HAp powder. md-HAp was characterized using FTIR and SEM analysis. There were four groups of GIC samples: (i) Fuji IX control group, (ii) powder modified with 3 wt% TiO2, (iii) powder modified with 3 wt% HAp, and (iv) powder modified with 1.5 wt% TiO2 + 1.5 wt% HAp. Measurements were performed in a universal testing machine, and CS, BS, and CM were calculated. Statistical analysis was performed using ANOVA and Tukey's tests. CS, BS, and CM differed significantly between the Fuji IX control group and all experimental groups while differences between the experimental groups were not statistically significant. The addition of TiO2 NP, md-HAp micro-sized particles, and a combination of TiO2 and md-HAp reduced the CS, BS, and CM of conventional GICs when mixed at the powder/liquid (p/l) ratio recommended by the manufacturer.

Influence of Home Composting on Tensile Properties of Commercial Biodegradable Plastic Films.

In recent years biodegradable plastic films have been increasingly used for various purposes, most often as grocery bags and for collecting bio-waste. Typically, the biodegradation of these films should take place in industrial compost facilities where the biodegradation process occurs under controlled conditions. Nevertheless, many of these films are often disposed of in home composting bins, so the aim of this study was to examine the course of biodegradation of compostable plastic films under uncontrolled conditions in garden composting sites during a period of four months. Mechanical properties were tested on seven different commercially available biodegradable films and bags that were placed in a garden composting bin from February to May. Both tensile properties and tensile-impact strength showed some unexpected results in terms of increase of the properties after the first, second, and third month for some films and bags. The same unpredictability was seen in FTIR and TG analyses.

Mechanical Properties of Glass Ionomer Cements after Incorporation of Marine Derived Porous Cuttlefish Bone Hydroxyapatite.

The purpose of this study was to evaluate the effects of the incorporation of hydroxyapatite (HA) derived from cuttlefish bone on the mechanical properties of glass ionomer cements (GIC). Fuji II LC and Fuji IX GP Extra (GC Corporation, Tokyo, Japan) were used in the study. There were four groups (n = 11-18) for each material: a group without the addition of HA particles and three groups modified by incorporation of 2, 5, and 10 wt% HA. The tests were performed on a universal testing machine (Shimadzu, Duisburg, Germany) and descriptive statistics, two-way analysis of variance (ANOVA) for the comparison of three mechanical properties, and one-way ANOVA for the comparison of different concentrations for each material were performed. Regarding the Fuji IX groups, compressive strength (CS) and flexural strength (FS) were highest in the group without HA particles added. The differences in CS between the Fuji IX group without HA particles and the Fuji IX groups with 2 wt% HA and 10 wt% HA were significant. The Fuji II 5 wt% HA group exhibited higher diametral tensile strength (DTS) and CS than other Fuji II groups, but not significantly. The Fuji II group, modified with 10 wt% HA, exhibited significantly higher FS than the Fuji II group without HA particles (p < 0.05). Porous HA incorporated into the Fuji IX groups had a significant impact on mechanical properties only in the Fuji IX 5 wt% HA group. Fuji II groups modified with 10 wt% HA showed the most favorable results with respect to FS.

Influence of Polymer Composites and Memory Foam on Energy Absorption in Vehicle Application.

The automotive industry is one of the biggest consumers of polymer composites. Aside from good mechanical properties, polymer composites have low mass, which positively affects the overall vehicle weight reduction and improves energy efficiency. Although polymer composites are used in various vehicle components, this paper focused on the application in vehicle bumper production. Two different composite plates with hybrid fiber layup were made; the first plate with a combination of glass and carbon fibers and the second with carbon and aramid. For comparison, and as a cheaper variant, a third plate was made only with glass fibers. In the first two plates, epoxy resin was used as the matrix, while in the third plate, polyester resin was used. Polyurethane memory foams of different densities (60, 80, 100 kg/m3) and thicknesses (10, 15, 20 mm) were used as impact force energy absorbers. With the factorial design of experiments, it was found that the thickness of the memory foam was the main influence factor. Without the use of memory foam, the hybrid composite, made of glass and carbon fibers, showed the highest energy absorption, while with the use of foam, the highest energy absorption was achieved with the glass fiber composite. Without the memory foam, the impact force measured on the glass/carbon hybrid composite was 9319.11 ± 93.18 N. Minimum impact force to the amount of 5143.19 ± 237.65 N was measured when the glass fiber composite plate was combined with the memory foam. When using memory foam, the impact force was reduced by 30%-48%, depending on the type of composite used.

Microreactor Production by PolyJet Matrix 3D-Printing Technology: Hydrodynamic Characterization§.

This work investigates the methodology of producing a 3D-printed microreactor from the acrylic resin by PolyJet Matrix process. The PolyJet Matrix technology employs different materials or their combinations to generate 3D-printed structures, from small ones to complex geometries, with different material properties. Experimental and numerical methods served for the evaluation of the geometry and production of the microreactor and its hydrodynamic characterization. The operational limits of the single-phase flow in the microchannels, further improvements and possible applications of the microreactor were assessed based on the hydrodynamic characterization.

Self-association of sodium isoursodeoxycholate and sodium isohenodeoxycholate in water.

Bile salts (BS) form hydrophobic Small's primary micelles at concentrations above the critical micelle concentration (CMC), while at concentrations above 3CMC they form secondary micelles (by the association of primary micelles via H-bonds). In this paper the self-associations of the anions of isohenodeoxycholic acid (3-epimer of henodeoxycholic acid, ICD) and the anions of isoursodeoxycholic acid (3-epimer of ursodeoxycholic acid, IUD) are examined, since the thermodynamic parameters of their self-association have not yet been published. Forming of IUD aggregates with two or three building units is slightly more favorable via α sides of steroid skeletons, regarding hydrophobicity, while regarding steric repulsive interactions it is more favorable to associate via ß sides. Due to this, IUD in the vicinity of the CMC can form primary micelles by association of IUD particles both from the convex side and from the concave side of the steroid ring system. Therefore, IUD is significantly more prone to initial micellization than bile salt derivatives whose steroidal skeletons contain equatorially oriented OH groups.

Influence of Processing Parameters on Tensile Properties of SLS Polymer Product.

Polymer products manufactured by additive processes are today increasingly flooding the market. Given that they have broad application ranging from various consumer products to medicine and automotive industry, the products must satisfy certain mechanical properties. In the past studies of selective laser sintering (SLS) for polymer materials, the processing parameter of energy density has been confirmed which affects the tensile properties. Energy density depends on the laser beam speed, laser power and hatch distance; however, in this paper the existing mathematical model has been expanded by the overlay ratio and tests have been conducted how on the basis of the new mathematical model a product with good tensile properties (tensile strength, tensile strength at break, tensile modulus, tensile strain at break) can be manufactured. However, in parameter selection as well, the layer thickness and the manufacturing strategy also play a role, and they may shorten the time and reduce the cost necessary to manufacture a new product from the initial concept to production. The paper also provides a proposal of processing parameters (laser beam speed, laser power and energy density) depending on the manufacturing strategy and layer thickness.

Importance of reversed-phase chromatographic parameters in predicting biopharmaceutical and pharmacokinetic descriptors on the group of androgen derivatives.

Nowadays the standard measure of lipophilicity, the logarithm of n-octanol-water partition coefficient, logP, is proposed to be replaced with chromatographic techniques. Chromatography techniques (reversed phase thin layer chromatography RPTLC and reversed phase thin layer chromatography RPHPLC) are the most widely used alternatives to the shake flask method. However, it is shown that, by changing the temperature or concentration of organic modifier in the chromatography experiment, it is possible to derive data matrix of retention parameters from which, by principle component analysis, structural characteristics of the examined molecules can be gained. The question may be asked which of the chromatography experimentally obtained and calculated parameters: capacity factor k, ΔGx (the change in Gibbs energy of binding of molecule for stationary phase), ΔHx (the change in enthalpy of binding of molecule for stationary phase) or ΔSx (the change in the entropy of binding of molecule for stationary phase) is the most suitable in describing hydrophobicity. The canonical correlation analysis (CCA) method is used to evaluate the importance of the n functions in explaining the variance of molecular descriptors connected to pharmaceutical processes and wherein molecule's hydrophobicity is expressed and possible differences between molecular descriptors with realistic conformations of the analyzed molecules steroid skeleton are discussed. Conformational analysis showed that structure of steroid skeleton in hydrophobicity is most completely described with k or ΔGx, and connection between conformation of the steroid skeleton and hydrophobicity to a lesser extent is projected on temperature dependence on ΔHx and similarly on ΔSx, so in describing molecules hydrophobicity it is necessary to observe entropic as well as enthalpic contribution together, expressed with ΔGx function. Canonical conformation analysis (CCA) showed that hydrophobicity contained in ΔGx and k explains 61% of variance represented in in silico descriptors. Analyzed molecular descriptors, derived from different molecules fragments don't map conformational specifics of those molecules in small groups so recommendation is to use them complementary with chromatographic data in describing hydrophobicity.

Antitumor activity of newly synthesized oxo and ethylidene derivatives of bile acids and their amides and oxazolines.

Bile acid derivatives with modifications in side chain and modifications on steroid skeleton were synthetized and their antitumor activity against five human cancer cell lines was investigated. Modifications in side chain include amid group, formed in reaction with 2-amino-2-methylpropanol, and 4,4-dimethyloxazoline group, obtained after cyclization of amides. In the steroid skeleton oxo groups were introduced in position 7 (2, 2a, 2b) and 7,12 (3, 3a, 3b). Ethylidene groups were introduced regio- and stereoselectively on C-7, and/or without stereoselectivity on C-3 by Wittig reaction. By combination of these modifications, a series of 19 bile acid derivatives were synthesized. Compounds containing both C-7 ethylidene and C-12 carbonyl groups (6, 6a, 6b) shown very good antitumor activity with IC50<5µM. Altering carboxylic group to amide or oxazoline group has positive effect on cytotoxicity. Different molecular descriptors were determined in silico and after principal component analysis was found that molecular descriptor BLTF96 can be used for fast assessment of experimental cytotoxicity of bile acid derivatives.

Challenges and opportunities of biodegradable plastics: A mini review.

The concept of materials coming from nature with environmental advantages of being biodegradable and/or biobased (often referred to as bioplastics) is very attractive to the industry and to the consumers. Bioplastics already play an important role in the fields of packaging, agriculture, gastronomy, consumer electronics and automotive, but still they have a very low share in the total production of plastics (currently about 1% of the about 300 million tonnes of plastic produced annually). Biodegradable plastics are often perceived as the possible solution for the waste problem, but biodegradability is just an additional feature of the material to be exploited at the end of its life in specific terms, in the specific disposal environment and in a specific time, which is often forgotten. They should be used as a favoured choice for the applications that demand a cheap way to dispose of the item after it has fulfilled its job (e.g. for food packaging, agriculture or medical products). The mini-review presents the opportunities and future challenges of biodegradable plastics, regarding processing, properties and waste management options.

pKa values of hyodeoxycholic and cholic acids in the binary mixed micelles sodium-hyodeoxycholate-Tween 40 and sodium-cholate-Tween 40: Thermodynamic stability of the micelle and the cooperative hydrogen bond formation with the steroid skeleton.

Due to a relatively small size of bile acid salts, their mixed micelles with nonionic surfactants are analysed. Of the special interests are real binary mixed micelles that are thermodynamically more stable than ideal mixed micelles. Thermodynamic stability is expressed with an excess Gibbs energy (GE) or over an interaction parameter (ßij). In this paper sodium salts of cholic (C) and hyodeoxycholic acid (HD) in their mixed micelles with Tween 40 (T40) are analysed by potentiometric titration and their pKa values are determined. Examined bile acids in mixed micelles with T40 have higher pKa values than free bile acids. The increase of ΔpKa acid constant of micellary bound C and HD is in a correlation with absolute values of an interaction parameter. According to an interaction parameter and an excess Gibbs energy, mixed micelle HD-T40 are thermodynamically more stable than mixed micelles C-T40. ΔpKa values are higher for mixed micelles with Tween 40 whose second building unit is HD, related to the building unit C. In both micellar systems, ΔpKa increases with the rise of a molar fraction of Tween 40 in binary mixtures of surfactants with sodium salts of bile acids. This suggests that, ΔpKa can be a measure of a thermodynamic stabilization of analysed binary mixed micelles as well as an interaction parameter. ΔpKa values are confirmed by determination of a distribution coefficient of HD and C in systems: water phase with Tween 40 in a micellar concentration and 1-octanol, with a change of a pH value of a water phase. Conformational analyses suggests that synergistic interactions between building units of analysed binary micelles originates from formation of hydrogen bonds between steroid OH groups and polyoxyethylene groups of the T40. Relative similarity and spatial orientation of C3 and C6 OH group allows cooperative formation of hydrogen bonds between T40 and HD - excess entropy in formation of mixed micelle. If a water solution of analysed binary mixtures of surfactants contains urea in concentration of 4M significant decreases of an interaction parameter value happens which confirms the importance of hydrogen bonds in synergistic interactions (urea compete in hydrogen bonds).

Comparison of dissolution profiles and serum concentrations of two lamotrigine tablet formulations.

BACKGROUND: Since 2005, the antiepileptic drug lamotrigine has been present in the market in various generic products, in addition to the original brand of Lamictal®. The linear pharmacokinetics and wide therapeutic window of lamotrigine enable seizure-free patients to easily switch from brand to generic antiepileptic drugs. OBJECTIVE: The aim of this study was to investigate the extent of variations in lamotrigine serum concentrations between two immediate-release tablet formulations. Data were compared with in vitro difference and similarity tests on dissolution profiles of the two formulations. METHODS: Dissolution characteristics of formulations A (reference) and B (test) were evaluated at three points spanning the physiologic pH range (pH 1.2, pH 4.5, pH 6.8). A model-independent approach of difference (f1) and similarity (f2) tests were applied to dissolution data. A clinical study was performed with 16 patients who were divided into two groups - one group received formulation A (n = 9) and the other received formulation B (n = 7). Lamotrigine steady-state concentrations were determined by high-performance liquid chromatography on a reverse-phase column. RESULTS: There were no statistically significant differences in lamotrigine serum concentrations between the two groups, although formulation B had slightly higher mean concentration values (formulation A: 3.97 ± 4.1 µg/mL; formulation B: 5.78 ± 2.7 µg/mL). Dissolution profiles of the two formulations were similar in the pH 1.2 dissolution medium; however, the dissolution profiles of formulation B were outside the dissolution limit (≥85% at 15 minutes) in the pH 4.5 and 6.8 dissolution media. CONCLUSIONS: No significant changes in the serum concentrations of lamotrigine were seen between the two investigated formulations. There is no evidence to suggest that the differences in dissolution profiles at pH 4.5 and pH 6.8 affect the therapeutic efficacy of the formulations. It is evident that the doses of test formulation given to the patients were higher as a consequence of common assumption that generic products have a lower absorption rate, which is proven unnecessary in this study. This investigation was a pilot study and thus further investigations with a larger sample size are necessary to determine if there is a connection between dissolution profiles and the therapeutic effect of investigated formulations.

Determination and importance of temperature dependence of retention coefficient (RPHPLC) in QSAR model of nitrazepams' partition coefficient in bile acid micelles.

Linear dependence between temperature (t) and retention coefficient (k, reversed phase HPLC) of bile acids is obtained. Parameters (a, intercept and b, slope) of the linear function k=f(t) highly correlate with bile acids' structures. Investigated bile acids form linear congeneric groups on a principal component (calculated from k=f(t)) score plot that are in accordance with conformations of the hydroxyl and oxo groups in a bile acid steroid skeleton. Partition coefficient (K(p)) of nitrazepam in bile acids' micelles is investigated. Nitrazepam molecules incorporated in micelles show modified bioavailability (depo effect, higher permeability, etc.). Using multiple linear regression method QSAR models of nitrazepams' partition coefficient, K(p) are derived on the temperatures of 25°C and 37°C. For deriving linear regression models on both temperatures experimentally obtained lipophilicity parameters are included (PC1 from data k=f(t)) and in silico descriptors of the shape of a molecule while on the higher temperature molecular polarisation is introduced. This indicates the fact that the incorporation mechanism of nitrazepam in BA micelles changes on the higher temperatures. QSAR models are derived using partial least squares method as well. Experimental parameters k=f(t) are shown to be significant predictive variables. Both QSAR models are validated using cross validation and internal validation method. PLS models have slightly higher predictive capability than MLR models.