Oxide Nanobelts as Conductometric Gas Sensors

Semiconducting oxide nanobelts have been obtained by vapor phase deposition. In this work we present the results obtained using tin oxide nanobelts as conductometric gas sensors. Electrical characterization showed that the nanobelts were sensitive to oxygen and environmental polluting species such as CO as well as ethanol for breath analyzers and food control applications. The sensor response, defined as the relative variation in conductance or resistance due to the introduction of the gas, is 200% for 30 ppm of CO at 623 K and 2500% for 10 ppm of ethanol at 623 K. We have studied the variation of the response as a function of the density of the nanobelts. The results demonstrate the potential of fabricating nanosize sensors using the integrity of a single nanobelt with sensitivity at the level of a few ppb and the necessity to control nanobelts density to optimize the sensing performances.     

Enhanced oral bioavailability of a poorly water soluble drug PNU-91325 by supersaturatable formulations

Supersaturatable cosolvent (S-cosolvent) and supersaturatable self-emulsifying drug delivery systems (S-SEDDS) are designed to incorporate water soluble cellulosic polymers such as hydroxypropyl methylcellulose (HPMC), which may inhibit or retard drug precipitation in vivo. A poorly soluble drug, PNU-91325, was used as a model drug in this study to illustrate this formulation approach. The comparative in vitro studies indicated that the presence of a small amount HPMC in the formulation was critical to achieve a stabilized supersaturated state of PNU-91325 upon mixing with water. An in vivo study was conducted in dogs for assessment of the oral bioavailability of four formulations of PNU-91325. A five-fold higher bioavailability (∼ 60%) was observed from a S-cosolvent formulation containing propylene glycol (PG) + 20 mg/g HPMC as compared to that (∼ 12%) of a neat polyethylene glycol (PEG) 400 formulation. The low bioavailability of the PEG 400 formulation is attributed to the uncontrolled precipitation of PNU-91325 upon dosing, a commonly observed phenomenon with the cosolvent approach. A S-SEDDS formulation composed of 30% w/w Cremophor (surfactant), 9% PEG 400, 5% DMA, 18% Pluronic L44, 20% HPMC, and other minor components showed an oral bioavailability of ∼ 76%, comparable to that of a neat tween formulation (bioavailability: ∼ 68%). The significant improvement of the oral bioavailability of the supersaturatable S-cosolvent and S-SEDDS formulations is attributed to a high free drug concentration in vivo as a result of the generation and stabilization of the supersaturated state due to the incorporation of polymeric precipitation inhibitor.     

Determination of steroid hormones in oral contraceptives by high-performance liquid chromatography

The aim of this research was to standardize a high-performance liquid chromatographic method for quantitative determination of steroid hormones, like ethinylestradiol (ETE), levonorgestrel (LEVO), and gestodene (GEST), in commercially available oral contraceptives (OCs). The combination ETE- LEVO was analyzed using a LiChrospher® 100 RP-8 column (5 μm, 125×4 mm) in LiChroCART®, with a mobile phase constituted of acetonitrile: water (60:40 v/v). Using the same column, ETE-GEST was analyzed with a mobile phase constituted of acetonitrile:water (50:50 v/v) at pH 7.5 adjusted with 0.02 M ammonium hydroxide. For both methods, a flow rate of 0.8 mL/min was utilized and detection was carried out at 215 nm. All analyses were performed at room temperature (24±2°C).

Calibration curves for ETE-LEVO were obtained using solutions with concentration ranges from 2.40 to 60.0 μg/mL (ETE), and from 12.0 to 300.0 μg/mL (LEVO). Calibration curves for ETE-GEST were obtained using solutions with concentration ranges from 2.40 to 60.0 μg/mL (ETE), and from 9.0 to 160.0 μg/mL (GEST). Correlation coefficients obtained were from 0.9999 to 0.9990. Coefficients of variation for samples containing ETE-LEVO were 0.47% and 0.38%, respectively. For samples with ETE-GEST they were 0.39% and 0.44%, respectively. The average recovery for samples with ETE-LEVO was 103.46% and 100.78%, respectively. For samples containing ETE-GEST it was 100.89% and 101.03%, respectively.     

Development of matrix patches for transdermal delivery of a highly lipophilic antiestrogen

The aim of this study was to develop matrix-type transdermal systems (TDSs) containing the highly lipophilic (log P = 5.82) antiestrogen (AE) and the permeation enhancers propylene glycol and lauric acid. For that purpose, permeation of AE from various adhesive matrices through excised skin of hairless mice was evaluated. It was found that pretreatment of the skin with permeation enhancers raised the transdermal flux of subsequently applied antiestrogen. Highest steady-state transdermal fluxes (1.1 µg cm^-2 h^-1) were obtained from Gelva®, polyacrylate adhesive, followed by 0.55 µg cm^-2 h^-1 from Oppanol® polyisobutylene, 0.31 µg cm^-2 h^-1 from BIO-PSA® silicone, and 0.12 µg cm^-2 h^-1 from Sekisui polyacrylate matrices. In order to develop TDS with high content of fluid permeation enhancer propylene glycol, two different strategies were investigated. One strategy was the addition of hydroxypropyl cellulose (HPC) as thickening agent to Gelva matrices. This allowed for propylene glycol loading levels of up to 30%, resulting in transdermal AE fluxes of 0.09 µg cm^-2 h^-1. On the other hand, a fleece-laminated backing foil was loaded with the described permeation enhancer formulation and laminated with polyacrylate adhesive layer, resulting in transdermal AE fluxes of 0.06 µg cm^-2 h^-1. However, application of these TDSs on skin pretreated with permeation enhancers raised the fluxes to 2.6 µg cm^-2 h^-1 from Gelva/HPC and 0.46 µg cm^-2 h^-1 from fleece/Sekisui.     

Ethyl cellulose and polyethylene glycol-based sustained-release sparfloxacin chip: an alternative therapy for advanced periodontitis

This study reports the development of a sustained-release system of sparfloxacin for use in the treatment of periodontal disease. A sustained-release sparfloxacin device was formulated, based on ethyl cellulose (EC) 10 cps, polyethylene glycol (PEG) 4000, and diethyl phthalate (DEPh). It will hereafter be called the sparfloxacin chip (SRS chip). The chip has dimensions of 10 mm length, 2 mm width, and 0.5 mm thickness. The in vitro drug release pattern and clinical evaluation of the formulations were studied. Reports of the short-term clinical study show that the use of the SRS chip may cause complete eradication of the pathogenic bacteria in the periodontal pockets of patients who have chronic generalized periodontitis. In this clinical study, the baseline and follow-up measurements of various clinical indices, such as oral hygiene index(es), plaque index, sulcular depth component of periodontal disease index, gingival crevicular fluid flow measurement, and dark field microscopic examinations of oral pathogens in plaque samples were studied. Significant improvements were observed in many parameters of the treatment group compared with the placebo group.     

Stability indicating HPTLC determination of linezolid as bulk drug and in pharmaceutical dosage form

A simple, selective, precise, and stability-indicating high-performance thin layer chromatographic method of analysis of Linezolid both as a bulk drug and in formulations was developed and validated in pharmaceutical dosage form. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of toluene-acetone (5:5, v/v). This system was found to give compact spots for Linezolid (R_f value of 0.29 ± 0.01). Linezolid was subjected to acidic, alkali hydrolysis, oxidation, and photodegradation. The degraded products also were well separated from the pure drug. Densitometric analysis of Linezolid was conducted in the absorbance mode at 254 nm. The linear regression data for the calibration plots showed good linear relationship with r² = 0.997 ± 0.001 in the concentration range of 300-800 ng/spot. The mean value of correlation coefficient, slope, and intercept were 0.998 ± 0.003, 0.15 ± 0.009, and 19.52 ± 1.66 respectively. The method was validated for precision, accuracy, ruggedness, and recovery. The limits of detection and quantification were 20 ng/spot and 50 ng/spot, respectively. The drug undergoes degradation under acidic and basic conditions, oxidation and photo degradation. All the peaks of degraded product were resolved from the standard drug with significantly different R_f values. This indicates that the drug is susceptible to acid-base hydrolysis, oxidation, and photo degradation. Statistical analysis proves that the method is reproducible and selective for the estimation of the said drug. Because the method could effectively separate the drug from its degradation products, it can be used as a stability indicating one.     

Spectroscopic Evidence for Anionic Coordination Complexes of the Transition Metals with C70 and the Higher Fullerenes C76, C78, C82, C84, C86, C90, and C92

The carbonylate anions [M(CO)₅]^- (M = Mn, Re), [Co(CO)₄]^-, [CpFe(CO)₂]^-, and [CpM(CO)₃]^- (M = Mo, W) react with C₇₀ via single electron transfer processes to give, respectively, the corresponding 17-electron, metal-centered radicals Co(CO)₄, M(CO)₅ (M = Mn, Re), CpFe(CO)₂, and CpM(CO)₃ (M = Mo, W) in addition to the radical anion C₇₀^-. In secondary thermal or photochemical processes, the metal-centered radicals Co(CO)₄ and M(CO)₅ (M = Mn, Re) combine with the C₇₀^- to form the new η²-C₇₀ complexes [Co(CO)₃(η²-C₇₀)]^- and [M(CO)₄(η²-C₇₀)]^-. However, the metal-centered radicals CpM(CO)₃ (M = Mo, W) require photolysis to react with C₇₀^- to form [CpM(CO)₂(η²-C₇₀)]^-, whereas neither thermolysis nor photolysis induces reaction between CpFe(CO)₂ and C₇₀^-. The photochemical reaction of [Mn(CO)₅]^- with a mixture of higher fullerenes known to contain at least C₇₆, C₇₈, C₈₄, C₈₆, and C₉₀ resulted similarly in the formation of the higher fullerene complexes [Mn(CO)₄(η²-C_n)]^- (n = 76, 78, 80, 82, 84, 86, 88, 90, 92, 96, and 98), all identified using electrospray mass spectrometry.     

Transdermal delivery of ondansetron hydrochloride: effects of vehicles and penetration enhancers

The effects of vehicles and penetration enhancers on the in vitro permeation of ondansetron hydrochloride (OS) across dorsal hairless mouse skins were investigated. Various types of vehicles, including ester, alcohol, and ether and their mixtures were used, and then a series of fatty acids and fatty alcohols were employed as enhancers. Among pure vehicles used, water and ethanol showed high permeation fluxes, which were 48.2 ± 23.7 and 41.9 ± 17.9 µg/cm² per h, respectively. Even though propylene glycol monocaprylate (PGMC) alone did not show a high permeation rate, the skin permeability of OS was increased by the addition of diethylene glycol monoethyl ether (DGME); the highest flux was achieved at 40% of DGME. Also, the combination of PGMC and ethanol (80:20) or PGMC and propylene glycol (PG) (60:40) increased the permeation flux by six- and two-fold, respectively, compared to PGMC alone. The synergistic enhancement was also obtained by using PG-oleyl alcohol (OAl) cosolvent. The greatest flux was attained by the addition of unsaturated fatty acids at 3% concentration to PG. The enhancement factors with the addition of oleic acid or linoleic acid to PG were about 1250 and 450, respectively. But saturated fatty acids failed to show a significant enhancing effect. When the PGMC-DGME (60:40) cosolvent system was used as a vehicle, all fatty acids, including unsaturated fatty acids, failed to show significant enhancing effects. The results indicate that the combinations of oleic acid, linoleic acid, or oleyl alcohol with PG, or PGMC-DGME (60:40) cosolvent could be used for the design of the OS transdermal system.     

Synthesis of a neodymium-quinolate complex for near-infrared electroluminescence applications

A structurally pure, near-infrared emissive Nd-(5,7-dichloro-8-hydroxyquinoline)₄ tetrakis complex has been synthesized. When incorporated as a dopant in the blue emissive, hole conducting polymer poly(N-vinylcarbazole), PVK, sensitized neodymium ion emission was observed following photo-excitation of the polymer host. OLED devices were fabricated by spin-casting layers of the doped polymer onto glass/indium tin oxide (ITO)/3,4-polyethylene-dioxythiophene-polystyrene sulfonate (PEDOT) substrates. An external quantum efficiency of 1 × 10^− 3% and a near-infrared irradiance of 2.0 nW/mm² at 25 mA/mm² and 20 V was achieved using glass/ITO/PEDOT/ PVK:Nd-(5,7-dichloro-8-hydroxyquinoline)₄/Ca/Al devices.     

Gadolinium-loaded nanoparticles engineered from microemulsion templates

Microemulsions (oil-in-water) have been used as templates to engineer stable emulsifying wax and Brij 72 (polyoxyl 2 stearyl ether) nanoparticles. The technique is simple, reproducible, and amenable to large-scale production of stable nanoparticles having diameters below 100 nm. Investigation of the process variables showed that the amount of surfactant used in the preparation of microemulsion templates had the greatest influence on the microemulsion window, as well as the properties and stability of the cured nanoparticles. Emulsifying wax and Brij 72 nanoparticles (2 mg/mL) made with 3 mM polyoxyl 20 stearyl ether and 2.3 mM polysorbate 80, respectively, were the most stable based on retention of nanoparticle size over time. Gadolinium acetylacetonate (GdAcAc), a potential anticancer agent for neutron capture therapy (NCT), was entrapped in stable nanoparticles. The apparent water solubility of GdAcAc was increased more than 2000-fold by entrapment into nanoparticles. The entrapment efficiency of GdAcAc was about 100% for emulsifying wax nanoparticles and 86% for Brij 72 nanoparticles, as determined by gel permeation chromatography (GPC). Elution profiles were obtained with light scattering (counts per second) to detect nanoparticles and ultraviolet (UV) absorption of GdAcAc at 288 nm. Challenges of these cured nanoparticles in biologically relevant media such as 10% fetal bovine serum, 10 mM phosphate-buffered saline, 150 mM NaCl, and 10% lactose at 37°C for 60 min demonstrated that these nanoparticles are stable. The ease of preparation of these very small and stable nanoparticles, and the ability to entrap lipophilic drugs such as GdAcAc with high efficiency, suggested that these systems may have potential in cell targeting, especially for specific delivery to tumor cells for NCT.     

Fiber Pretreatment and Its Effects on Wood Fiber Reinforced Polypropylene Composites

This study investigates the effect of pretreatment of fiber with NaOH and coupling with maleated polypropylene (MAPP) on the physical and mechanical properties of composites, based on radiata pine (Pinus Radiata) fiber, produced with a polypropylene matrix, using a twin-screw extruder followed by injection molding. Prior to reinforcement, the fiber was treated with NaOH. The effect of treatment was assessed using zeta potential, scanning electron microscopy (SEM), and X-ray diffraction (XRD). Tensile testing, SEM, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) were carried out to assess the effect of modification on composite properties. An increase of 106% for strength and 302% for Young's modulus were obtained by using 60 wt% fiber and 2 wt% MAPP, compared to the unreinforced matrix. Fiber pretreatment with NaOH reduced strength but improved Young's modulus (370% compared to unreinforced matrix) of resulted composite.     

Simultaneous Deposition of Powder in Three Parallel-Oriented Cylindrical Dies

The inhomogeneity of bulk density distribution created during the die filling process might cause quality problems for powder compacts, such as distortion, lamination, and cracking. To avoid these problems, understanding the die filling process and ensuring a uniform pre-compaction powder deposition are necessary. The second-generation pressure deposition tester (PDT-II) was developed to investigate simultaneous deposition of powder into multiple dies. Its design requirements and new features were proposed through evaluating the main strength and limitations of the mass deposition tester (MDT). The operation of the PDT-II and analysis of its data showed that it generates real-time deposition profiles of the entire process for multiple locations. PDT-II data can be used to study the effects of various filling-related parameters (such as die shape, powder flowability, and feed shoe speed) on the deposition process and final pressure distribution. For cylindrical dies filled with a granulated powder with d₅₀ = 600 μm (1) at low feed shoe speeds (20 and 100 mm/s), the half circle close to the leeward end had higher final pressure values than the forward half circle; (2) at high feed shoe speed (500 mm/s), the final pressure distribution was more uniform than at lower feed shoe speed; (3) the final within-die pressure distribution at the bottom of the dies was not always symmetrical about the center line of the feed shoe movement direction, even though sometimes it was quite symmetrical; (4) the overall trend was that pressure decreases with increasing radial distance for lower feed shoe speeds; and (5) higher feed shoe speed (500 mm/s) resulted in higher final pressure values (774.5 to 1424.5 Pa) than lower feed shoe speeds (20 and 100 mm/s) (235.2 to 1136.0 Pa) at most of the locations. The results proved that feed shoe speed does have an effect on pressure distribution and its uniformity.     

Application of fluidized hot-melt granulation (FHMG) for the preparation of granules for tableting; properties of granules and tablets prepared by FHMG

The objective of this study was to investigate the properties of granules and tablets prepared by a novel Fluidized Hot-Melt Granulation (FHMG) technique. Macrogol 6000 (polyethylene glycol 6000, PEG 6000), macrogol 20000 (polyethylene glycol 20000, PEG 20000), and glyceryl monostearate (GMS) were used as binders with different levels of viscosity and water solubility. The properties of both granules and tablets were compared with those obtained using the Standard Tablet Formulation (STF, lactose/corn starch/hydroxypropylcellulose/magnesium stearate: 66/30/3.5/0.5) for fluidized-bed granulation, which is widely used for wet granulation. To obtain suitable flowability as granules for tabletting, the content of the melting material should be approximately 10 w/w%. The rate of increase in the mean diameter of the granules during FHMG was affected by both the melting temperature and the viscosity of the melting material used in the granules. The compression properties of granules prepared by FHMG were also investigated, demonstrating that these granules had a high pressure transmittance. The hardness and the disintegration time of tablets obtained from granules prepared by FHMG were influenced by the properties of the melting material, such as its compaction behavior, solubility, and wettability. No significant differences of hardness were observed when compared to STF tablets. Tablets prepared from FHMG granules disintegrated within 15 min, whereas the STF tablets showed faster disintegration. It was also demonstrated that the hardness and disintegration time of tablets prepared from FHMG granules were not affected by the tablet porosity. Therefore, tablets with a constant quality may be obtainable under a wide range of compression forces. The results of this study suggested that FHMG is a useful method of preparing granules for tableting without using any solvents or water.     

In vitro skin permeation and retention of paromomycin from liposomes for topical treatment of the cutaneous leishmaniasis

Paromomycin (PA), a very hydrophilic antibiotic, has been tested as an alternative topical treatment against cutaneous leishmaniasis (CL). Although this treatment has shown promising results, it has not been successful in accelerating the recovery in most cases. This could be attributed to the low skin penetration of PA. Liposomal formulations usually provide sustained and enhanced drug levels in skin. The aim of this study was to prepare liposomal formulations containing PA and to investigate their potential as topical delivery systems of this antileishmanial. Large multilamellar vesicles (MLVs) were prepared by conventional solvent evaporation method. Large unilamellar vesicles (LUVs) were prepared by reverse-phase evaporation method. The lipids used were soybean phosphatidylcholine (PC) and PC:cholesterol (CH) (molar ratio 1:1). The skin permeation experiments across stripped and normal hairless mice skin were performed in modified Franz diffusion cells. The PA entrapment in LUV liposomes (20.4 ± 2.2%) was higher than that observed for MLV liposomes (7.5 ± 0.9%). Drug entrapment was 41.9 ± 6.2% and 27.2 ± 2.4% for PC and PC:CH LUV, respectively. The skin permeation was 1.55 ± 0.31%, 1.29 ± 0.40%, 0.20 ± 0.08%, and 0.50 ± 0.19% for PC LUV, PC:CH LUV, empty LUV + PA and aqueous solution, respectively. Controlled topical delivery, across stripped skin, was observed for PA entrapped in LUV liposomes.     

Comparison of three pharmaceutical products obtained from Mexico and the United States: a case study

In recent years, there has been much debate concerning the relative pros and cons of purchasing medications from foreign markets such as Mexico and Canada. The following study compares the content uniformity and weight variation for three medicinal products, acquired from pharmacies in both Mexico and the United States: amoxicillin capsules (500 mg), amoxicillin/clavulanic acid suspension (400 mg and 57 mg/5 mL, respectively), and furosemide tablets (40 mg). Twenty capsules/tablets were individually weighed and a designated aliquot was taken. Following dissolution in an appropriate solvent and sonication, a sample was taken and analyzed via high performance liquid chromatography (HPLC). The suspensions were prepared according to directions on the label. Five samples of the suspensions were then taken and analyzed via an appropriate HPLC method. The content uniformity for the amoxicillin capsules was found to be 15.4 ± 2.4% and 99.4 ± 9.3%, for Mexican and U.S. capsules, respectively. The percent relative standard deviation (% RSD) for weight variation was found to be 8.7% and 1.5% for capsules obtained from Mexico and the United States, respectively. Content uniformity analysis for the Mexican suspension product resulted in an average of 85.5 ± 1.2% for amoxicillin and 98.6 ± 1.9% for the clavulanic acid content, while the results for the U.S. suspension product were 104.4 ± 3.1% and 117.8 ± 3.6% for amoxicillin and clavulanic acid, respectively. Content uniformity for the furosemide tablets was found to be 90.3 ± 4.8% and 95.6 ± 2.1% for Mexican and U.S. tablets, respectively. The % RSD of weight variation for the Mexican tablets was 2.1%, while the % RSD for the U.S. tablets was found to be 1.0%. From the three products tested, content analysis revealed that the amount of active ingredients for two of the products acquired in Mexico were appreciably less than the concentrations for their U.S. counterparts.     

Polysaccharides as excipients for colon-specific coatings. Permeability and swelling properties of casted films

Oligosaccharides such as inulin (In) and polysaccharides such as galactomannans, combined with polymethacrylates on isolated films for film coatings, were obtained from aqueous-based solvents and investigated as potential vehicles for colonic drug delivery. These compositions, which are susceptible to fermentation by colonic microflora, constitute promising excipients for the development of new colon-specific therapeutic systems. The characteristics of several compositions have been demonstrated in permeability and swelling studies on isolated films composed of a polymethacrylate associated with In or galactomannans of mesquite seed gum (MSG). Results reported prove a dependency of the properties of mixed films on the polymethacrylate-polysaccharide concentration ratio and on the composition of the dissolution media. An increase in permeability through the mixed films was observed in a simulated colonic environment for the following compositions: Eudragit®RS30D-MSG 70 : 30 w/w; Eudragit® RS30D-In 90 : 10 w/w; Eudragit®RS30D-In 76 : 24 w/w.     

Tape Cast Multilayer Composite of Nano Zirconia with High Toughness

During the last decade, worldwide attention of researchers has focused on nano-ceramic composites with superior mechanical behavior and improved reliability for structural applications. Here we report the development of a multi-layer composite (MLC) of tape cast nano zirconia with high failure energy. The MLC samples were fabricated by thermocompression of green tapes prepared from 3 mole % yttria stabilized zirconia (3-YSZ) powder with a primary crystallite size of 27 nm. Depending on the number of layers, the MLC samples exhibited failure energy (238.97 KJm^-3) more than two times higher than that of the single tape (≈107 KJm^-3) with a reasonably high bi-axial flexural strength (≈630 MPa), high hardness (≈ 13 GPa at 49 N), and indentation fracture toughness nearly four times as high as that of the single tape. In addition, these MLC materials showed the presence of a R-curve behavior.     

Design and evaluation of matrix diffusion controlled transdermal patches of verapamil hydrochloride

Transdermal patches of verapamil hydrochloride were prepared using four different polymers (individual and combination): Eudragit RL100 (ERL100), Eudragit RS100 (ERS100), hydroxypropyl methylcellulose 15 cps (HPMC), and ethyl cellulose (EC), of varying degrees of hydrophilicity and hydrophobicity. The effect of the polymers on the technological properties, i.e., drug release, water vapor transmission rate (WVTR), and percentage moisture loss (ML), percentage moisture absorption (MA), folding endurance, and thickness, was investigated. Different formulations were prepared in accordance with the 2³ factorial design, with ERL100 being the parent polymer. The patch containing ERL100 alone showed maximum WVTR, % MA, and % ML, which could be attributed to its hydrophilic nature. As expected, substitution with ERS100, HPMC, and EC decreased all the above values in accordance with their decreasing degree of hydrophilicity. In vitro release studies showed zero-order release of the drug from all the patches, and the mechanism of release was diffusion mediated. Moreover, the release of the drug was sustained and it extended over a period of 24 hr in all formulations. A12 emerged as the most satisfactory formulation insofar as its technological properties were concerned. Further, release and permeation of the drug from the most satisfactory formulation (A12) was evaluated through different biological barriers (shed snake skin, rabbit skin, and rat skin) to get an idea of the drug permeation through human skin. Shed snake's skin was found to be most permeable (82.56% drug release at 24 hr) and rat skin was least permeable (52.38%). Percutaneous absorption studies were carried out in rabbits. The pharmacokinetic parameters calculated from blood levels of the drug revealed a profile typical of a sustained release formulation, with the ability to maintain adequate plasma levels for 24 hr. [AUC: 3.09 mg/mL hr, C_max: 203.95 µg/mL, T_max: 8 hr]. It can therefore be concluded that the patch containing ERL100 and HPMC in the ratio 8:2 has achieved the objectives of transdermal drug delivery system, such as avoidance of first pass effect, extended release, and reduced frequency of administration.     

Modeling of the Transient Particle Velocity Distribution in the Fluidized Bed Combustor (FBC) Riser

The geometrical distributions of transient particle velocity in a fluidized bed combustor (FBC) riser are critical to FBC design and manufacturing. Particle image velocimetry (PIV) instrumentation was applied to visualize the particle transient movement in the area of interest (AOI) of an experimental cold model (152 mm ID × 610 mm height) of an FBC. Sixteen (16) PIV particle velocity profiles were generated for the AOI in a 1.6-second time period. A ten (columns) × five (rows) grid was set for each profile. Three levels of fluidizing air velocity were set for the experiments at 2.477 m/s, 2.677 m/s, and 2.823 m/s respectively. A knowledge-based regression method was applied to generate the empirical model of the two-dimensional particle transient velocity with the consideration of four independent variables, x (x coordinate), y (y coordinate), V_g (fluidizing air velocity), and t (time). This model had a data fitting accuracy of 88%. In addition, this model had a very good validation performance with the data obtained from other tests at different experimental setups.

The modeling method is applied for the first time to the particle movement in FBC risers. The research work proved that the design of the experiment and regression analysis are very effective and practical for evaluating experimental conditions and analyzing experimental results in FBC systems.     

Preformulation studies for an ultrashort-acting neuromuscular blocking agent GW280430A. I. Buffer and cosolvent effects on the solution stability

GW280430A is an ultrashort-acting neuromuscular blocking agent targeted at muscle relaxation to facilitate surgical intubation. The objective of this work was to study the buffer and cosolvent effects on the solution stability of GW280430A. The buffer catalytic effect was examined in citrate, malate, tartrate, and glycine by measuring the rate of degradation of GW280430A (0.2 mg/mL) at constant pH (3), ionic strength (0.15 M), and various buffer concentrations (0.01-0.05 M). The temperature dependence of the buffer catalytic effect and the degradation of the GW280430A in cosolvent (ethanol, propylene glycol, polyethylene glycol 400, N,N-dimethylacetamide)/water mixtures were studied at 40, 50, and 60°C. The loss of parent drug was monitored by reverse-phase high-performance liquid chromatography. The degradation of GW280430A followed first-order kinetics in all buffer solutions. Significant buffer-catalyzed hydrolysis of GW280430A was observed with citrate, tartrate, and malate buffers, but not in glycine-buffered solutions. The activation energies in all buffered drug solutions ranged from 70 to 80 kJ/mol and decreased with increasing buffer concentration. GW280430A degradation was primarily through ester hydrolysis and followed first-order kinetics in aqueous solutions. In cosolvent/water mixtures, new degradation products were observed, indicating a chemical reaction between GW280430A and cosolvents. The reaction activation energies in the cosolvent/water mixtures ranged from 75 to 85 kJ/mol, with the longest t_0.9 at 5°C equal to approximately 12 months and at 25°C equal to 36 days. Consideration should be given to the incorporation of glycine or a low concentration of citrate, malate, or tartrate buffer in the parenteral formulation development of GW280430A. Cosolvents prolonged the predicted t_0.9 for GW280430A in solution, but the enhancement was not significant enough to pursue a liquid formulation.