Process and formulation variables of pregabalin microspheres prepared by w/o/o double emulsion solvent diffusion method and their clinical application by animal modeling studies

Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. In conventional therapy recommended dose for pregabalin is 75?mg twice daily or 50?mg three times a day, with maximum dosage of 600?mg/d. To achieve maximum therapeutic effect with a low risk of adverse effects and to reduce often drug dosing, modified release preparations; such as microspheres might be helpful. However, most of the microencapsulation techniques have been used for lipophilic drugs, since hydrophilic drugs like pregabalin, showed low-loading efficiency and rapid dissolution of compounds into the aqueous continous phase. The purpose of this study was to improve loading efficiency of a water-soluble drug and modulate release profiles, and to test the efficiency of the prepared microspheres with the help of animal modeling studies. Pregabalin is a water soluble drug, and it was encapsulated within anionic acrylic resin (Eudragit S 100) microspheres by water in oil in oil (w/o/o) double emulsion solvent diffusion method. Dichloromethane and corn oil were chosen primary and secondary oil phases, respectively. The presence of internal water phase was necessary to form stable emulsion droplets and it accelerated the hardening of microspheres. Tween 80 and Span 80 were used as surfactants to stabilize the water and corn oil phases, respectively. The optimum concentration of Tween 80 was 0.25% (v/v) and Span 80 was 0.02% (v/v). The volume of the continous phase was affected the size of the microspheres. As the volume of the continous phase increased, the size of microspheres decreased. All microsphere formulations were evaluated with the help of in vitro characterization parameters. Microsphere formulations (P1–P5) exhibited entrapment efficiency ranged between 57.00?±?0.72 and 69.70?±?0.49%; yield ranged between 80.95?±?1.21 and 93.05?±?1.42%; and mean particle size were between 136.09?±?2.57 and 279.09?±?1.97?µm. Pregabalin microspheres having better results among all formulations (Table 3) were chosen for further studies such as differential scanning calorimetry, Fourier transform infrared analysis and dissolution studies. In the last step, the best pregabalin microsphere formulation (P3) was chosen for in vivo animal studies. The pregabalin-loaded microspheres (P3) and conventional pregabalin capsules were applied orally in rats for three days, resulted in clinical improvement of cold allodynia, an indicator of peripheral neuropathy. This result when evaluated together with the serum pregabalin levels and in vitro release studies suggests that the pregabalin microspheres prepared with w/o/o double emulsion solvent diffusion method can be an alternative form for neuropathic pain therapy. Conclusively, a drug delivery system successfully developed that showed modified release up to 10?h and could be potentially useful to overcome the frequent dosing problems associated with pregabalin conventional dosage form.     

An integrated system design environment: Concepts and a status report

In the construction of requirements specifications for a given problem, it is generally recommended that overspecification of the problem solution be avoided [1]. Such overspecification tends to distort the functionality required by suggesting implementation concepts at the outset. In order to avoid overspecification, and to provide a support environment to the specifier, a four-stage system design environment is proposed and has been partially implemented over a three-year period. The theoretical basis of this approach is explained in [2]. Our system-level specification language (DODAN) is developed in [3]. Based on this specification language, a prototype (DAA) [4, 5, 6] for supporting the requirements specification stage has been implemented. Our other protype (DARMS) addressing the module specification stage was developed in [7, 8]. In this paper, the current status of the project is described with an emphasis on the requirements specification stage.     

Poly(3-Octylthiophene) and Poly(3-Octylthiophene)/TiO2-Coated on Al1050: Electrosynthesis,Characterization and Its Corrosion Protection Ability in NaCl Solution

In this study, 3-octylthiophene (3OT) and its nanocomposites with TiO₂(3OT/TiO₂) were electrochemically synthesized in different initial monomer concentrations (50, 75, 100, and 150 mM) in 0.1 M tetraethylammonium tetrafluoroborate (TEABF₄)/acetonitrile (CH₃CN) on a glassy carbon electrode (GCE). The best modified electrodes, which were taken from the optimum conditions of redox behaviors, were also electropolymerized in 0.5 M oxalic acid/acetonitrile (CH₃CN) solution on Al1050 electrode. The modified Al1050 electrodes were characterized by optical microscope, FTIR-ATR, SEM-EDX, and EIS. The optimum conditions of the electrocoated P(3OT)/Al1050 and P(3OT)/TiO₂ nanocomposites on Al1050 electrode were investigated for corrosion performances against 3.5% NaCl solution. The corrosion tests were performed by EIS and Tafel extrapolation plots together with the equivalent circuit model of R_s(Q_c(R_c(Q_pR_ct))). P(3OT)/TiO₂ nanocomposite films showed higher protection efficiency (PE = 89%) than P(3OT) films (PE = 81%). The P(3OT)/TiO₂ nanocomposite films coated on Al1050 electrodes may be used in industrial applications of corrosion protection against salt water.     

Physicochemical,sensorial and rheological characterisation of whole-fat or low-fat milk jams as influenced by calcium chloride,sodium bicarbonate and sucrose content

Rheological properties of sixteen milk jam treatments produced from commercial full-fat (3 g/100 g) and skimmed (0.15 g/100 g) cow milk by the addition of sucrose, sodium bicarbonate and CaCl₂ were examined. pH, titratable acidity, total solids and ash contents in the milk jam samples ranged from 6.2 to 6.8, 1.3 to 3.3 g/100 g, 56.7 to 70.5 g/100 g and 1.7 to 3 g/100 g, respectively, with a significant variability (P < 0.05). The flow behaviour and consistency indices ranged from 0.7 to 0.9 and 2.7 to 208 Pa.sn, respectively. Rheological measurements showed that the maximal G' × 10² value showed considerable variation (5–932 Pa). As sucrose content increased, pH and total solid content increased, whereas ash content and the L value decreased. Also, a negative correlation between pH and L* (lightness) was found (P < 0.05). Dynamic rheology showed that the jam from skimmed milk with full sucrose and without sodium bicarbonate exhibited more solid-like behaviour than the ones prepared with full sucrose and with sodium bicarbonate. In conclusion, the increase in milk fat caused a decrease in resistance of the mixture subjected to the deformation, which is very important for production of quality milk jam.     

Synthesis and properties of alkoxysilane-functionalized styrenated oil based polyester

Alkoxysilane-functionalized styrenated oil based polyester hybrid films were prepared by using vinyl trimethoxysilane (VTMS) as an inorganic source. For this purpose, an oil based polyester (PGMA) was first synthesized by the esterification of partial glyceride (PG) mixture with maleic anhydride (MA). Then, PGMA was further reacted with both styrene (St) and the mixture of St and VTMS yielding St–PGMA and St–PGMA–VTMS samples, respectively. The synthesis was carried out by changing VTMS content in the range of 5–15 wt.% in order to investigate the effect of inorganic domains on the film properties. While the films of St–PGMA–VTMS were formed on the appropriate substrates by moisture curing and oxidative polymerization, St–PGMA films were only cured by oxidative polymerization. The characterization of the polymers was done by FTIR, ¹H NMR, DSC, TGA and SEM. FTIR and DSC analyses indicated the completion of the moisture curing process. Film properties such as flexibility, adhesion, water, alkali and acid resistances were determined. All samples showed good film properties. Moreover, in comparison, St–PGMA–VTMS samples exhibited better alkali resistance than St–PGMA due to the contribution of the inorganic domains.     

Estimation of monthly diffuse nutrient loads for a watershed in Turkey

Diffuse pollution has a complex nature depending on various land‐use activities like agriculture, livestock breeding and forestry. In this study, an alternative methodology is applied for decreasing the spatial uncertainty of diffuse nutrient load estimations. It is applied in the Melen Watershed, Turkey, which is an important watershed from where additional water will be supplied for the megacity Istanbul via interbasin water transfer. Monthly diffuse nutrient loads were estimated for each subwatershed by utilizing remote sensing (RS) and geographical information systems (GIS). Estimated nutrient loads were considerably different in various months due to the temporally irregular fertilizer application and meteorological conditions. Temporal differences were also predicted in the spatial distribution of the nutrient loads. The methodology is applicable in watershed protection studies, especially where necessary etudes should be conducted in the short term and with limited data. Such efforts in identifying and determining the diffuse loads are important for sustainable management of the watershed.     

Grafting tomato plant on tobacco plant and its effect on tomato plant yield and nicotine content

BACKGROUND: Two different tomato scions, cv. Elazig and cv. Sweet (cherry) (Solanum lycopersicum L.) were self‐grafted and grafted onto tobacco root stock (Nicotiana tobacum L.). Then, grafted tomato plants were evaluated in terms of flower and fruit yield. Tobacco‐grafted tomato plant fruits were also evaluated for nicotine content. RESULTS: Tobacco grafting had a positive effect on the tomato plant cultivation performance; the onset of flowering was almost 15 days earlier and the tomato flower and fruit yields increased in both tomato cultivars. Tobacco grafting resulted in 5.0% and 30.1% increase in total fruit weight for cv. Sweet and cv. Elazig, respectively. Because the level of nicotine was within acceptable ranges, tobacco‐grafted tomato fruits were considered to be safe for consumption. Self‐grafted tomato cultivars also had flowering time onsets almost 11 days earlier. However, self‐grafting caused 6.0% and 7.6% less total fruit yield per cv. Sweet and cv. Elazig, respectively. CONCLUSION: In conclusion, our results show that tomato–tobacco grafting is a novel and promising technique for improvement of not only tomato plant performance and yield, but also that it can be employed to various tomato varieties. Copyright © 2009 Society of Chemical Industry     

Arsenite removal from groundwater in a batch electrocoagulation process: Optimization through response surface methodology

In this study, influences of seven process variables such as initial pH (pH_i), applied current (i), operating time (t_EC), initial As(III) concentration (C_o), diameter of Fe ball anode (d_p), column height in the electrocoagulation (EC) reactor (h) and airflow rate (Q_air) for removal of As(III) from groundwater by a new air-fed fixed-bed EC reactor were evaluated with a response surface methodology (RSM). The proposed quadratic model fitted very well with the experimental data for the responses. The removal efficiencies and operating costs were determined to be 99% and 0.01 $/m³ at the optimum operating conditions (a pH_i of 8.5, 0.05 A, 4.94 min, d_p of 9.24 mm, h of 7.49 cm, Q_air of 9.98 L/min for 50 µg/L). This study clearly showed that the RSM in the EC process was a very suitable method to optimize the operating conditions at the target value of effluent As(III) concentration (10 µg/L) while keeping the operating cost to minimal and maximize the removal efficiency.     

Progressive transmission of images over fading channels using rate-compatible LDPC codes.

In this paper, we propose a combined source/channel coding scheme for transmission of images over fading channels. The proposed scheme employs rate-compatible low-density parity-check codes along with embedded image coders such as JPEG2000 and set partitioning in hierarchical trees (SPIHT). The assignment of channel coding rates to source packets is performed by a fast trellis-based algorithm. We examine the performance of the proposed scheme over correlated and uncorrelated Rayleigh flat-fading channels with and without side information. Simulation results for the expected peak signal-to-noise ratio of reconstructed images, which are within 1 dB of the capacity upper bound over a wide range of channel signal-to-noise ratios, show considerable improvement compared to existing results under similar conditions. We also study the sensitivity of the proposed scheme in the presence of channel estimation error at the transmitter and demonstrate that under most conditions our scheme is more robust compared to existing schemes.