Topical Oleo-Hydrogel Preparation of Ketoprofen with Enhanced Skin Permeability

In an attempt to improve the skin penetration of ketoprofen, various transdermal formulations were prepared, and their in vitro skin permeability and in vivo percutaneous absorption were evaluated. In vitro permeation studies were performed using a modified Franz cell diffusion system in which permeation parameters such as cumulative amount at 8 hr Q_8hr, steady-state flux J_ss, or lag time t_L were determined. In the in vivo percutaneous absorption study using the hairless mouse, maximum concentration C_max and area under the curve at 24 hr AUC_24h were measured. The optimal transdermal formulation (oleo-hydrogel formulation) of ketoprofen showed a Q_8hr value of 227.20 μg/cm², a J_ss value of 29.61 μg/cm²/hr, and a t_L value of 0.46 hr. The Q_8hr and J_ss values were about 10-fold (p <. 01) higher than those (Q_8hr = 19.61 μg/cm²; J_ss = 2.66 μg/cm²/hr) from the K-gel and about 3.5-fold (p <. 01) than those (Q_8hr = 60.00 μg/cm²; J_ss = 7.99 μg/cm²/hr) of the K-plaster. In the in vivo percutaneous absorption, the C_max (6.82 μg/ml) and AUC_24h (55.74 μg·hr/ml) values of the optimal formulation were significantly (p <. 01) higher than those of K-gel and K-plaster. The relative bioavailability of the oleo-hydrogel following transdermal administration in reference to oral administration was about 37%, and the C_max value (4.73 μg/cm²) in the hypodermis following topical administration was much higher than those from the conventional products (C_max of K-gel and K-plaster were 0.92 ± 0.19 μg/cm² and 1.27 ± 0.37 μg/cm², respectively). These data demonstrate that the oleo-hydrogel formulation of ketoprofen was more beneficial than conventional products (K-gel and K-plaster) in enhancing transdermal permeation and skin absorption of ketoprofen. Furthermore, there was a good correlation between in vitro permeation parameters and in vivo percutaneous absorption parameters.     

Pharmacokinetics of Ketoprofen After Intravenous and Intramuscular Administrations to Rabbits

Abstract

The pharmacokinetics of ketoprofen was studied in rabbits following intravenous and intramuscular administrations of ketoprofen, both at a dose of 4.0 mg.Kg^-1. Plasma levels of ketoprofen, as a function of time, were determined by a reversed-phase high performance liquid chromatography. The disposition of ketoprofen was described by a two-compartment open model with elimination from the central compartment. A model-independent method using the statistical moment theory was also applied. Pharmacokinetics of ketoprofen was characterized as a drug with terminal half-life of 3.15 hr, low apparent volumes of distribution (V = 0.031 L.Kg^-1, Vd_ss = 0.070 L.Kg^-1 and Vd_β = 0.130 L.Kg^c-1). The mean residence time (MRT) was found to be 1.44 hr for i.v. injection and 2.86 hr for i.m. injection. The clearance (CL) and apparent volume of distribution at steady state (Vd_ss) after i.v. injection was determined to be 0.027 L.Kg^-1.hr^-1 and 0.03 9 L.Kg^-1, respectively. The absorption rate constant from the limb muscle site into systemic circulation was calculated to be 2.19 hr^-1 and peak plasma concentration after i.m. injection was observed to be at 0.31 ± 0.11 hr. The systemic availability of ketoprofen after intramuscular administration was determined to be 0.38, relative to the equal i.v dose.     

Disposition of the Flavonoid Quercetin in Rats After Single Intravenous and Oral Doses

Abstract

The pharmacokinetic and mean time tissue distribution parameters, after a single 50-mg/kg dose of quercetin administered as intravenous bolus, oral solution, and oral suspension, were determined using rat as an animal model. Following intravenous administration, the elimination rate constant and the elimination half-life were found to be 0.0062 min^?1 and 111 min, respectively. Examining the mean time tissue distribution parameters reflected a strong binding affinity of the drug molecules to both plasma and tissue proteins. In addition, the low permeability rate of drug molecules in the peripheral system was demonstrated. Following the oral administration of the drug, the extent of absorption was greater from solution than from suspension. Moreover, the solution showed a shorter T_max and a higher C_max than suspension. The absolute bioavailability for the solution was 0.275 and that for suspension was 0.162. The mean residence time (MRT) and the mean absorption time (MAT) were higher for suspension, reflecting the need for dissolving the drug in order to be absorbed. The mean (in-vivo) dissolution time (MDT_in-vivo) was 34.5 min. Thus, an oral quercetin formulation that can readily form a drug solution in the gastrointestinal tract may enhance the absorption of the drug.     

Preparation,characterization and in vitro and in vivo evaluation of a solid dispersion of Naringin

Naringin (NA) is one of typical flavanone glycosides widely distributed in nature and possesses several biological activities including antioxidant, anti-inflammatory, and antiapoptotic. The aim of this study was to develop solid dispersion (SD) and to improve the dissolution rate and oral bioavailability of NA. NA–SD was prepared by the traditional preparation methods using PEG6000, F68, or PVP K30 as carrier at different drug to carrier ratios. According to the results of solubility and in vitro dissolution test, the NA–PEG6000 (1:3) SD was considered as an optimal formulation to characterize by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry and powder X-ray diffraction. Furthermore, oral bioavailabilities of NA–PEG6000 (1:3) SD and NA–suspension with the same dosage were investigated in SD rats. The results confirmed the formation of SD and the pharmacokinetic parameters of NA–PEG6000 (1:3) SD (C_max?=?0.645?±?0.262?µg/ml, AUC_0–t?=?0.471?±?0.084?µg/ml?h) were higher than that of NA–suspension (C_max?=?0.328?±?0.183?µg/ml, AUC_0–t =?0.361?±?0.093?µg/ml?h). Based on the results, the SD is considered as a promising approach to enhance the dissolution rate and oral bioavailability of NA.     

Relative Bioavailability and Pharmacokinetic Parameters Following Adminstration of Single Oral Dose (2×150 mg) of Chloroquine Tablet in Healthy Subjects

Abstract

The bioavailability ot Chloroquine phosphate (150 mg base) film coated tablet (manufactured by Pars - Darou Co. Iran) was compared with that ot the Resochin tablet (Bayer, Germany) in seven healthy male and female volunteers. Blood samples were collected up to 14 days utter oral dosing of 300 nig and chloroquine serum concentrations were determined by means ot High Performance Liquid Chromatography (HPLC). From the analysis ot serum samples the following pharmacokinetic parameters were obtained: the absorption rate of test tablet and that of reference were 0.25 h^?1 and 0.34 h^?1 respectively; maximum serum concentration of both tablets was nearly equal, 81.6±25 and 83.4±27 ng/ml (for test and reference tablets respectively); time to reaching C_max (t_max) was also very similar, 4±1.6 for test and 4±1.0 h for reference; the area under the serum concentration-time curve [AUC(O -)] of 6976 ng.ml^?1.h±1967 for test and 6446 ng.ml^?1.h ± 2460 for reference tablets were found using trapezoidal rule. By evaluating of the r=(T/R)×100 for each parameters, the test tablet was found to be bioequivalent to Resochin at p = 0.05.     

Tables of the Inverse Laplace Transform of the Function [... formula ...]

The inverse transform, g(t) = ?^?1(e^?sβ), 0 < β < 1, is a stable law that arises in a number of different applications in chemical physics, polymer physics, solid-state physics, and applied mathematics. Because of its important applications, a number of investigators have suggested approximations to g(t). However, there have so far been no accurately calculated values available for checking or other purposes. We present here tables, accurate to six figures, of g(t) for a number of values of β between 0.25 and 0.999. In addition, since g(t), regarded as a function of β, is uni-modal with a peak occurring at t = t_max we both tabulate and graph t_max and 1/g(t_max) as a function of β, as well as giving polynomial approximations to 1/g(t_max).     

Rational Construction of Hollow Core‐Branch CoSe2 Nanoarrays for High‐Performance Asymmetric Supercapacitor and Efficient Oxygen Evolution

Metal selenides have great potential for electrochemical energy storage, but are relatively scarce investigated. Herein, a novel hollow core‐branch CoSe₂ nanoarray on carbon cloth is designed by a facile selenization reaction of predesigned CoO nanocones. And the electrochemical reaction mechanism of CoSe₂ in supercapacitor is studied in detail for the first time. Compared with CoO, the hollow core‐branch CoSe₂ has both larger specific surface area and higher electrical conductivity. When tested as a supercapacitor positive electrode, the CoSe₂ delivers a high specific capacitance of 759.5 F g^?1 at 1 mA cm^?2, which is much larger than that of CoO nanocones (319.5 F g^?1). In addition, the CoSe₂ electrode exhibits excellent cycling stability in that a capacitance retention of 94.5% can be maintained after 5000 charge–discharge cycles at 5 mA cm^?2. An asymmetric supercapacitor using the CoSe₂ as cathode and an N‐doped carbon nanowall as anode is further assembled, which show a high energy density of 32.2 Wh kg^?1 at a power density of 1914.7 W kg^?1, and maintains 24.9 Wh kg^?1 when power density increased to 7354.8 W kg^?1. Moreover, the CoSe₂ electrode also exhibits better oxygen evolution reaction activity than that of CoO.     

Process optimization of spray-dried fanhuncaoin powder for pulmonary drug delivery and its pharmacokinetic evaluation in rats

The optimization of process parameters of spray-dried powder containing fanhuncaoin, a newly discovered anti-inflammatorily active phenolic acid isolated from Chinese herb, was conducted using response surface methodology (RSM). The experimental results were fitted into partial cubic polynomial model to describe and predict the response quality in terms of the final angle of repose, aerodynamic diameter, respirable fraction (RF), and yield. The recommended optimum spray-drying parameters for the development of fanhuncaoin powder with optimum quality were 110?°C inlet temperature, 0.50 m³/min aspiration speed, and 7.95?ml/min feed flow rate. The obtained optimum process parameters were employed for the production of spray-dried fanhuncaoin powder and to check the validity of the partial cubic model. Small and insignificant deviations were found between the predicted values and the experimental ones, showing the efficiency of the model in predicting the quality attributes of fanhuncaoin powder. The optimized powder was further examined for its pharmacokinetic properties in rats. A UPLC/MS assay was used to determine plasma fanhuncaoin concentration. Statistical analysis demonstrated that there was no significant difference in the t_1/2 and dose-normalized C_max and AUC as well as other pharmacokinetic parameters between the groups dosed differently following intratracheal administration (p?>?.05), indicating that fanhuncaoin followed linear kinetics. The pharmacokinetic parameters of fanhuncaoin after intratracheal administration differed significantly from the ones observed after intravenous administration (p?C_max and AUC_(0-∞) obtained following intratracheal administration may lead to effective drug concentrations at the target site with minimal systemic bioavailability and side effects.     

Tissue distribution and targeting evaluation of TMP after oral administration of TMP-loaded microemulsion to mice

The aim of this study was to quantify the oral delivery systems of Tetramethylpyrazine Microemulsion (TMP ME) to heart, liver, spleen, lung, kidney and brain by comparing TMP level after oral administration at a dose of 100?mg kg^?1 with those of TMP tablet suspension (TMP SWW). This study was taken in mice to develop a suitable analytical methodology in pharmacokinetics studies and to manipulate the tissue distribution and targeting evaluation. Drug concentrations in tissues were determined at different times post-mortem. An HPLC method for separation and quantification of TMP was developed and validated by studying mice tissues. Following oral administration, TMP concentrations in different tissues were constantly detected for quite a long time and finally differed significantly from each other. The AUC rank order 3 of ME group is AUC_liver?> AUC_brain?> AUC_lung?> AUC_spleen?> AUC_heart?> AUC_kidney, while the SWW group is AUC_liver?> AUC_lung?> AUC_spleen?> AUC_heart?> AUC_brain?> AUC_spleen. Especially, the AUC value in brain region (AUC_brain) of ME is 6.06-fold of SWW. The drug relative overall targeting efficiency (RTE) are calculated: heart (7.49%), liver (3.54%), spleen (12.60%), lung (6.02%), kidney (2.86%) and brain (12.51%). The results from ME directly showed obvious targeting transport to the brain. These results indicated that this new family of pharmaceutical carriers can be used for the solubilization and targeted delivery of poorly soluble drugs to various pathological sites in the body.     

Fabrication of novel GMO/Eudragit E100 nanostructures for enhancing oral bioavailability of carvedilol

In the present work, novel nanostructures comprising of glyceryl monooleate (GMO) and Eudragit E100 were prepared using high intensity ultrasonic homogenization. 3² Factorial design approach was used for optimization of nanostructures. Results of regression analysis revealed that the amount of GMO and Eudragit E100 had a drastic effect on particle size and percent entrapment efficiency. Optimized carvedilol-loaded nanostructures (Car-NS) were characterized by FTIR, TEM, DSC, in vitro drug release study. Pharmacokinetic parameters such as C_max, T_max, Ke, Ka, V_d and AUC were estimated for Car-NS upon its oral administration in Sprague-Dawley rats. Particle size of Car-NS was found to be 183?±?2.43?nm with an entrapment efficiency of 81.4?±?0.512%. FTIR studies revealed loading and chemical compatibility of carvedilol with the components of nanostructures. DSC thermograms did not show endothermic peak for melting of carvedilol which could be attributed to solubilization of carvedilol in molten GMO during DSC run. The prepared Car-NS released carvedilol in sustained manner over a period of 10 h as suggested by in vitro drug release study. The pharmacokinetic study of Car-NS showed significant improvement in C_max (two fold, p?p?相似文献   

Fabrication of a 3D Hierarchical Sandwich Co9S8/α‐MnS@N–C@MoS2 Nanowire Architectures as Advanced Electrode Material for High Performance Hybrid Supercapacitors

Supercapacitors suffer from lack of energy density and impulse the energy density limit, so a new class of hybrid electrode materials with promising architectures is strongly desirable. Here, the rational design of a 3D hierarchical sandwich Co₉S₈/α‐MnS@N–C@MoS₂ nanowire architecture is achieved during the hydrothermal sulphurization reaction by the conversion of binary mesoporous metal oxide core to corresponding individual metal sulphides core along with the formation of outer metal sulphide shell at the same time. Benefiting from the 3D hierarchical sandwich architecture, Co₉S₈/α‐MnS@N–C@MoS₂ electrode exhibits enhanced electrochemical performance with high specific capacity/capacitance of 306 mA h g^?1/1938 F g^?1 at 1 A g^?1, and excellent cycling stability with a specific capacity retention of 86.9% after 10 000 cycles at 10 A g^?1. Moreover, the fabricated asymmetric supercapacitor device using Co₉S₈/α‐MnS@N–C@MoS₂ as the positive electrode and nitrogen doped graphene as the negative electrode demonstrates high energy density of 64.2 Wh kg^?1 at 729.2 W kg^?1, and a promising energy density of 23.5 Wh kg^?1 is still attained at a high power density of 11 300 W kg^?1. The hybrid electrode with 3D hierarchical sandwich architecture promotes enhanced energy density with excellent cyclic stability for energy storage.     

Abnormal da/dN – ΔK curves: New failure mode with Ti – alloys

Fatigue crack propagation (FCP) -rates and -threshold values have been determined on the titanium alloys IMI 834, IMI 685 (turbine disk materials) and Ti-6Al-6V-2Sn (plate material). K_max-constant tests were executed in laboratory air at room temperature and run with 50 Hz on C(T) specimens. It was found that FCP-rates in K_max-constant tests followed the well known FCP behavior up to a certain limiting value K_max, denoted as °K_max. Below °K_max, the FCP-rates da/dN decrease with decreasing ΔK down to the threshold value ΔK_T (ΔK for 10^?7 mm/cycle). For K_max-constant tests with K_max > °K_max, the FCP-rates initially decreased with decreasing ΔK, but reached 10^?7 mm/cycle at smaller ΔK. For K_max ≧ ∧K_max > °K_max, FCP-rates of 10^?7 mm/cycle were never reached as ΔK decreased to and below ΔK_T. Instead, as ΔK approaches or gets smaller than ΔK_T, the FCP-rates stay either constant or increase again. The limit value °K_max for this abnormal FCP-behavior had been determined for IMI 834 to be 22 to 28 MPa√m, for IMI 685 to be 46 MPa√m and for Ti-6A1–6V-2Sn to be 26 MPa√m. The important result from a practical stand-point is the large difference in °K_max for comparable Ti alloys, i.e., IMI 834 and IMI 685.     

Comparison of the Bioavailability of oral and Rectal forms of Diphenylhydantoin Sodium

Abstract

The bioavailabilities of single 100-mg oral and rectal doses of diphenylhydantoin sodium were studied in five healthy volunteers. The rectal form used was prepared at laboratory conditions and the oral form was a commercial preparation. Blood samples were analysed over a 72-hr period. Evaluation of the AUC, t_max and C_max values have shown that the total absorption after the two routes of administration was the same while the C_max and t_max differed.     

Non-ionic surfactant based vesicular drug delivery system for topical delivery of caffeine for treatment of cellulite: design,formulation, characterization,histological anti-cellulite activity,and pharmacokinetic evaluation

Cellulite is a common topographical alteration where skin acquires an orange peel or mattress appearance with alterations in adipose tissue and microcirculation. This work aims to develop and evaluate a topical niosomal gel formulae with good permeation to reach the subcutaneous fat layer. Several caffeine niosomal dispersions were prepared and incorporated into gel formulae using Carbopol 940 polymer, chemical penetration enhancers, and iontophoresis, then the prepared gels were applied onto the skin of rats and anticellulite activity of caffeine from the prepared gels compared to that of the commercial product Cellu Destock^® was evaluated by histological study of the skin and measurement of plasma level of caffeine passing through the skin using liquid chromatography (LC/MS–MS). Results of histology revealed reduction of size and thickness of fatty layer of rat skin in the following order: FVII?>?FXIV?>?Cellu Destock^®?>?FVII?+?Iontophoresis?>?FXIV?+?Iontophoresis. Pharmacokinetic results of caffeine in plasma revealed that C_max, T_max, and AUC_0–12h decreased in the following order: FXIV?>?FVII?>?Cellu Destock^®. These results conclude that incorporation of caffeine niosomal dispersion into gel matrix with penetration enhancers and iontophoresis resulted in improvement in penetration of caffeine through the skin into the underlying fatty layer in treatment of cellulite.     

The effect of clopidogrel on pharmacokinetics of ivabradine and its metabolite in rats

The present study aimed to investigate the effect of clopidogrel (CLO) on pharmacokinetics of ivabradine (IVA) and its metabolite in rats and develop a reliable method to determine IVA and its metabolite N-demethyl ivabradine in serum. Healthy male SD rats were randomized to be given 0.8?mg/kg IVA or IVA combined with 8?mg/kg CLO. Blood samples were collected at 0.083, 0.16, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24?h after administration. The serum concentrations of IVA and N-demethyl ivabradine were determined by ultra-performance liquid chromatography–mass spectrometry and pharmacokinetic parameters were calculated using DASver3.0 software. The parameters of AUC_(0???t), AUC_(0???∞), and C_max for IVA in the group of IVA?+?CLO were significantly higher than those in the group of IVA (p?t_1/2) in the IVA?+?CLO group was extended compared to IVA (p?p?(0???_t), AUC_(0???∞), and C_max for N-demethyl ivabradine in the group of IVA?+?CLO was significantly compared to the group of IVA (p?p?t_1/2 was slightly increased. In this study, we find that CLO restrains the metabolism of IVA into N-demethyl ivabradine, which may be related to its competitive inhibition effect on cytochrome P450 isoform 3A4(CYP3A4).     

Degradation of tobramycin in aqueous solution

Abstract

The kinetics of degradation of tobramycin (Ne-De-Ka) in aqueous solution was studied as a function of pH. Tobramycin hydrolyzes in acidic solution to yield kanosamine (Ka-OH) and nebramine (Ne-De-OH) with a pseudo first-order rate constant of 2.7 × 10^?6 s^?1 in 1 N HCl at 80°C. The activation energy for the acid catalyzed hydrolysis is 32 kcal mol^?1. In basic solution, the hydrolysis products are deoxystreptamine (De-OH), nebramine (Ne-De-OH) and deoxystreptamine-kanosaminide (HO-De-Ka). The pseudo first-order rate constant for the hydrolysis in 1 N KOH is 1 × 10^?8 s^?1 at 80°C. The activation energy for the base catalyzed hydrolysis is 15 kcal mol^?1. Tobramycin is very stable towards hydrolysis at neutral pH; however, it rapidly oxidizes giving several products including De-OH, Ne-De-OH, and HO-De-Ka. In pH 7 phosphate buffer (0.01 M), the t₉₀ value is 70 hr at 80°C.     

Beyond Activated Carbon: Graphite‐Cathode‐Derived Li‐Ion Pseudocapacitors with High Energy and High Power Densities

Supercapacitors have aroused considerable attention due to their high power capability, which enables charge storage/output in minutes or even seconds. However, to achieve a high energy density in a supercapacitor has been a long‐standing challenge. Here, graphite is reported as a high‐energy alternative to the frequently used activated carbon (AC) cathode for supercapacitor application due to its unique Faradaic pseudocapacitive anion intercalation behavior. The graphite cathode manifests both higher gravimetric and volumetric energy density (498 Wh kg^?1 and 431.2 Wh l^?1) than an AC cathode (234 Wh kg^?1 and 83.5 Wh l^?1) with peak power densities of 43.6 kW kg^?1 and 37.75 kW l^?1. A new type of Li‐ion pseudocapacitor (LIpC) is thus proposed and demonstrated with graphite as cathode and prelithiated graphite or Li₄Ti₅O₁₂ (LTO) as anode. The resultant graphite–graphite LIpCs deliver high energy densities of 167–233 Wh kg^?1 at power densities of 0.22–21.0 kW kg^?1 (based on active mass in both electrodes), much higher than 20–146 Wh kg^?1 of AC‐derived Li‐ion capacitors and 23–67 Wh kg^?1 of state‐of‐the‐art metal oxide pseudocapacitors. Excellent rate capability and cycling stability are further demonstrated for LTO‐graphite LIpCs.     

Preparation, evaluation and bioavailability studies of indomethacin-bees wax microspheres

The present study envisages the preparation of microspheres containing indomethacin (IM) as model drug and bees wax as carrier, and to compare the in vitro release and pharmacokinetics of prepared IM formulation with commercially available oral formulation Microcid^®SR. The microsphere formulations were prepared by meltable emulsified dispersion and cooling induced solidification. Surface morphology of microspheres has been evaluated using scanning electron microscopy (SEM). The SEM images revealed the spherical shape of microspheres and more than 98.0% of the isolated microspheres were in the size range 115–855 μm. Differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy studies indicated that the drug after encapsulation with bees wax was stable and compatible. A single dose randomized complete cross over study of IM (75 mg) microspheres was carried out on 8 healthy Albino sheeps. Plasma IM concentrations and other pharmacokinetic parameters obtained were statistically analyzed. The T _max, C _max, AUC_O-24 and T _1/2 values of Microcid^®SR and optimized formulation were 3.0 h, 2038 ± 51.31 ng/ml, 9528 ± 129.65 ng/ml h^?1, and 2.59 ± 0.02 h^?1; and 3.2 h, 1940 ± 22.61 ng/ml, 8751 ± 41.32 ng/ml h^?1, and 2.68 ± 0.02 h^?1, respectively. Beeswax microspheres showed controlled release and it can be concluded that both the prepared formulation and Microcid^®SR are bioequivalent.     

Sildenafil vaginal suppositories: preparation,characterization, in vitro and in vivo evaluation

Aim: The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS).

Methods: Suppositories containing 25?mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated.

Results: The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127?±?0.020?g, 98.25?±?2.50%, 2.5?±?0.08?kg and 9?±?1.0?min, respectively. The release of sildenafil from the SVS was more than 90% at 30?min, with a release kinetic of Hixson--Crowell model and non-Fickian diffusion (n?=?0.464). The plasma PK study demonstrated a significantly lower C_max (～10 times) and AUC_0–24?h (～13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher C_max (～40 times) and AUC_0–24?h (～20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution.

Conclusion: This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.     

Experiments on high excitation density, quenching, and radiative kinetics in CsI:Tl scintillator

Information on quenching as a function of electron-hole density through the range of 10¹⁹ to 2×10²⁰ e-h/cm³ typically deposited towards the end of an electron track has been acquired using 0.5 ps pulses of 5.9 eV light to excite in the band-to-band or high-exciton region of CsI and CsI:Tl. A streak camera records partially quenched luminescence from self-trapped excitons (STE) and excited activators (Tl^+?). Both the Tl^+? and STE luminescence exhibit decreasing light yield versus excitation density N_max, but it is only the 302 nm STE luminescence that exhibits decay time quenching dependent on N_max. Fitting the STE decay time data to a model of dipole-dipole quenching yields the time-dependent bimolecular rate constant for quenching of STEs (and Tl^+? light yield) in CsI at room temperature: k₂(t)=2.4×10⁻¹⁵ cm³ s^−1/2 (t^−1/2).