China Science

The purpose of this research was to analyze the pharmacological properties of a homologous series of nitrogen mustard (N-mustard) agents formed after inserting 1 to 9 methylene groups (-CH2-) between 2-N(CH2CH2Cl)2 groups. These compounds were shown to have significant correlations; associations in their properties after analysis by pattern recognition methods including hierarchical classification, cluster analysis, nonmetric multi-dimensional scaling (MDS), detrended correspondence analysis, K-means cluster analysis, discriminant analysis,; self-organizing tree algorithm (SOTA) analysis. Detrended correspondence analysis showed a linear-like association of the 9 homologs,; hierarchical classification showed that each homolog had great similarity to at least one other member of the series—as did cluster analysis using paired-group distance measure. Nonmetric multi-dimensional scaling was able to discriminate homologs 2; 3 (by number of methylene groups) from homologs 4, 5,; 6 as a group,; from homologs 7, 8,; 9 as a group. Discriminant analysis, K-means cluster analysis,; hierarchical classification distinguished the high molecular weight homologs from low molecular weight homologs. As the number of methylene groups increased the aqueous solubility decreased, dermal permeation coefficient increased, Log P increased, molar volume increased, parachor increased,; index of refraction decreased. Application of pattern recognition methods discerned useful interrelationships within the homologous series that will determine specific; beneficial clinical applications for each homolog; methods of administration.

Ronald Bartzatt1Email:bartzatt@mail.unomaha.edu?Laura Donigan1
[1] Department of Chemistry, Laboratory of Pharmaceutical Studies, University of Nebraska, Durham Science Center, 6001 Dodge St, 68182 Omaha, NE

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing metoprolol tartrate (MT) as a model drug by the optimization technique. A 2[3] factorial design was employed in formulating the GFDDS with total polymer content-to-drug ratio (X1), polymer-to-polymer ratio (X2),; different viscosity grades of hydroxypropyl methyl cellulose (HPMC) (X3) as independent variables. Four dependent variables were considered: percentage of MT release at 8 hours, T50%, diffusion coefficient,; floating time. The main effect; interaction terms were quantitatively evaluated using a mathematical model. The results indicate that X1; X2 significantly affected the floating time; release properties, but the effect of different viscosity grades of HPMC (K4M; K10M) was nonsignificant. Regression analysis; numerical optimization were performed to identify the best formulation. Fickian release transport was confirmed as the release mechanism from the optimized formulation. The predicted values agreed well with the experimental values,; the results demonstrate the feasibility of the model in the development of GFDDS.

C. Narendra1Email:narendragcp@rediffmail.com?M. S. Srinath2?Ganesh Babu2
[1] Department of Pharmaceutics, Krupanidhi College of Pharmacy, Bangalore-34, India ;[2] Department of Pharmaceutics, Government College of Pharmacy, Bangalore-27, India ;[3] Department of Pharmaceutics, Visveswarapura Institute of Pharmaceutical Sciences, V.V. Puram, 560004 Bangalore, Karnataka, India

Conclusions Depending on the dose size; solubility characteristics of low solubility drugs, a meaningful; discriminatory power of dissolution rate testing can be demonstrated. Saturation solubility of fenofibrate; glipizide in different media were determined. Solubility of fenofibrate increased directly with SLS concentration. For a 54-mg fenofibrate tablet, SLS at 0.025 M level is required for a discriminative dissolution test, while for 160-mg tablet, dissolution condition; levels of SLS should be optimized; higher concentrations may be effective (ie, 0.052 M, ?1.5%). A pH 6.8 phosphate buffer medium is appropriate for glipizide 10-mg tablet dissolution study, when formulation ingredients include excipients with surface activity (eg, HPMC).

Shahla Jamzad1?Reza Fassihi1Email:reza.fassihi@temple.edu
[1] School of Pharmacy, Temple University, 3307 N Broad Street, 19140 Philadelphia, PA

The objective of this study was to develop an efficient tumor vasculature targeted liposome delivery system for combretastatin A4, a novel antivascular agent. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, distearoyl phosphoethanolamine-polyethylene-glycol-2000 conjugate (DSPE-PEG),; DSPE-PEG-maleimide were prepared by the lipid film hydration; extrusion process. Cyclic RGD (Arg-Gly-Asp) peptides with affinity for ?v?3-integrins expressed on tumor vascular endothelial cells were coupled to the distal end of PEG on the liposomes sterically stabilized with PEG (long circulating liposomes, LCL). The liposome delivery system was characterized in terms of size, lamellarity, ligand density, drug loading,; leakage properties. Targeting nature of the delivery system was evaluated in vitro using cultured human umbilical vein endothelial cells (HUVEC). Electron microscopic observations of the formulations revealed presence of small unilamellar liposomes of ?120 nm in diameter. High performance liquid chromatography determination of ligand coupling to the liposome surface indicated that more than 99% of the RGD peptides were reacted with maleimide groups on the liposome surface. Up to 3 mg/mL of stable liposomal combretastatin A4 loading was achieved with ?80% of this being entrapped within the liposomes. In the in vitro cell culture studies, targeted liposomes showed significantly higher binding to their target cells than non-targeted liposomes, presumably through specific interaction of the RGD with its receptors on the cell surface. It was concluded that the targeting properties of the prepared delivery system would potentially improve the therapeutic benefits of combretastatin A4 compared with nontargeted liposomes or solution dosage forms.

Ramakrishna Nallamothu1Email:rnallamo@utmem.edu?George C. Wood1?Christopher B. Pattillo2?Robert C. Scott2?Mohammad F. Kiani2?Bob M. Moore4?Laura A. Thoma1
[1] Parenteral Medications Laboratories, Department of Pharmaceutical Sciences, University of Tennessee Health Sciences Center, TN, 26 S Dunlap St, Room 214, 38163 Memphis, TN ;[2] Department of Mechanical Engineering, Temple University, Philadelphia, PA ;[3] Department of Radiation Oncology, Temple University, Philadelphia, PA ;[4] Department of Pharmaceutical Sciences, University of Tennessee Health Sciences Center, Memphis, TN

The purpose of this study was to evaluate the change of surface roughness; the development of the film during the film coating process using laser profilometer roughness measurements, SEM imaging,; energy dispersive X-ray (EDX) analysis. Surface roughness; texture changes developing during the process of film coating tablets were studied by noncontact laser profilometry; scanning electron microscopy (SEM). An EDX analysis was used to monitor the magnesium stearate; titanium dioxide of the tablets. The tablet cores were film coated with aqueous hydroxypropyl methylcellulose,; the film coating was performed using an instrumented pilot-scale side-vented drum coater. The SEM images of the film-coated tablets showed that within the first 30 minutes, the surface of the tablet cores was completely covered with a thin film. The magnesium signal that was monitored by SEM-EDX disappeared after ?15 to 30 minutes, indicating that the tablet surface was homogeneously covered with film coating. The surface roughness started to increase from the beginning of the coating process,; the increase in the roughness broke off after 30 minutes of spraying. The results clearly showed that the surface roughness of the tablets increased until the film coating covered the whole surface area of the tablets, corresponding to a coating time period of 15 to 30 minutes (from the beginning of the spraying phase). Thereafter, the film only became thicker. The methods used in this study were applicable in the visualization of the changes caused by the film coating on the tablet surfaces.

Paulus Seitavuopio1Email:paulus.seitavuopio@helsinki.fi?Jyrki Hein?m?ki1?Jukka Rantanen2?Jouko Yliruusi1
[1] Faculty of Pharmacy, Division of Pharmaceutical Technology, University of Helsinki, PO Box 56, 00014 Helsinki, Finland ;[2] Drug Discovery Technology Center, University of Helsinki, PO Box 56, 00014 Helsinki, Finland

In spite of being sheared along the so-called pseudo-twinning direction, ?-TiAl undergoes true twinning under zero pressure or hydrostatic tension by means of a specific combination of , and shears in two consecutive (1 1 1) matrix planes allowing the adjacent twin to thicken over one (1 1 1) atomic layer. The corresponding total shear strain of is four times as large as that generated by conventional deformation twinning or during the L10 to L11 transformation by or shears, respectively. This shear is substantially more effective in accommodating stress concentration and high strain rate than conventional deformation twinning. The conditions under which twinning by dislocations operates are interpreted based on a modified gamma-surface and discussed in terms of zonal partial dislocations.

Dongsheng XuaEmail:dsxu@imr.ac.cn?Hao Wanga?Rui Yanga?Patrick Veyssièreb
[a]Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, China;[b]LEM, CNRS-ONERA, BP 72, 92322 Chatillon, France

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Macroscopic deformation modes, elastic, uniform plastic, and unstable plastic deformation modes, are mapped in tensile true stress–dose space for more than two dozen metallic materials consisting of 13 body-centered cubic (bcc), 11 face-centered cubic (fcc), and two hexagonal closed packed (hcp) metals. The boundaries between different deformation zones are set by the true stress versus dose curves: the yield stress (YS), plastic instability stress (PIS), and true fracture stress (FS) plotted as functions of dose. Values for these true stresses are obtained from uniaxial tensile tests or calculated from engineering tensile data using a linear strain-hardening model for necking deformation. The relatively low-strength annealed fcc metals display large uniform plasticity regions, while unstable deformation regions are dominant in the harder bcc and hcp metals. PIS values for all materials are independent of dose except for the precipitation-hardened IN718 alloy, where a decrease of PIS occurs due to an irradiation-induced change in second phases. In the bcc materials for high-temperature application, such as 9Cr ferritic/martensitic steels, sintered molybdenum, vanadium, and tantalum, the radiation-induced embrittlement is characterized in terms of FS decreasing with dose at relatively high doses. FS is nearly dose-independent below the critical dose for embrittlement. It is concluded that the tensile stress-based deformation mode maps effectively integrate mechanical property information and characterize differences in radiation effects between crystalline structures or material groups.

Thak Sang ByunaEmail:byunts@ornl.gov?Kenneth Farrella?Meimei Lia
[a]Oak Ridge National Laboratory, P.O. Box 2008, MS-6151, Oak Ridge, TN 37831, USA

The orientation stability in equal channel angular extrusion (ECAE) of hexagonal close-packed (hcp) crystals using a 90° die is investigated based on the three-dimensional lattice rotation fields from rate-dependent crystal plasticity simulations. The results show that for the major slip and twinning modes considered, the relatively stable orientations in ECAE are distributed along the h1? to h6? fibers in the Euler space and feature characteristic alignments of the a- or c-axis with respect to the macroscopic deformation axes. The application of such simulations is demonstrated by comparing the predictions with experimental ECAE textures in high-purity titanium and other hcp polycrystalline materials, including commercial-purity zirconium, beryllium and magnesium alloys. The simulation results for ECAE are also applied to derive the relatively stable orientations in conventional simple shear deformation.

Saiyi LiaEmail:saiyi@scut.edu.cn
[a]School of Mechanical Engineering, South China University of Technology, Guangzhou 510640, China