Mucoadhesive, syringeable drug delivery systems for controlled application of metronidazole to the periodontal pocket: In vitro release kinetics, syringeability, mechanical and mucoadhesive properties

Novel mucoadhesive formulations containing hydroxyethylcellulose (HEC; 3 and 5%, w/w) or Carbopol (3 and 5%, w/w), polycarbophil (PC; 1 and 3%, w/w) and metronidazole (5%, w/w) at pH 6.8 were designed for the treatment of periodontal diseases. Each formulation was characterised in terms of hardness, compressibility, adhesiveness and cohesiveness (using Texture Profile Analysis), drug release, adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode) and, finally, syringeability (using the texture analyser in compression mode). Drug release from all formulations was non-diffusion controlled. Drug release was significantly decreased as the concentration of each polymeric component was increased, due to both the concomitant increased viscosity of the formulations and, additionally, the swelling kinetics of PC following contact with dissolution fluid. Increasing the concentrations of each polymeric component significantly increased formulation hardness, compressibility, adhesiveness, mucoadhesion and syringeability, yet decreased cohesiveness. Increased product hardness, compressibility and syringeability were due to polymeric effects on formulation viscosity. The effects on cohesiveness may be explained both by increased viscosity and also by the increasing semi-solid nature of products containing 5% HEC or Carbopol and PC (1 or 3%). The observations concerning formulation adhesiveness/mucoadhesion illustrate the adhesive nature of each polymeric component. Greatest adhesion was noted in formulations where neutralisation of PC was maximally suppressed. For the most part, increased time of contact between formulation and mucin significantly increased the required force of detachment, due to the greater extent of mucin polymer hydration and interpenetration with the formulations. Significant statistical interactions were observed between the effects of each polymer on drug release and mechanical/mucoadhesive properties. These interactions may be explained by formulatory effects on the extent of swelling of PC. In conclusion, the formulations described offered a wide range of mechanical and drug release characteristics. Formulations containing HEC exhibited superior physical characteristics for improved drug delivery to the periodontal pocket and are now the subject of long-term clinical investigations. (C) 1997 Elsevier Science B.V.

Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers

This study examined the mechanical/textural, viscoeiastic and mucoadhesive properties of a range of aqueous gels composed of either hydroxyethylcellulose (HEC) or sodium carboxymethylcellulose (Na CMC). The mechanical/textural properties of each formulation were determined using texture profile analysis. The viscoelastic properties of each formulation were examined over a defined frequency range (0.01-1.0 Hz) using oscillatory rheometry in conjunction with stainless steel parallel plate geometry. The mucoadhesive properties of the gels were evaluated by measuring the tensile force required to overcome the gel/mucin adhesive interaction. Both gel hardness and compressibility, properties that affect the ease of product removal from a container and spreadability, increased as a function of increasing polymer concentrations. This is attributed to the effects of HEC and Na CMC on gel viscosity. Gel adhesiveness, a property related to bioadhesion, also increased as a function of polymer concentration and is attributed to the reported adhesive nature of these polymers. Increasing frequency of oscillation increased the storage and loss moduli yet decreased bath the dynamic viscosity of each gel type and also the loss tangent of HEC (but not Na CMC) gels. Therefore, following exposure to the range of oscillatory stresses that may be expected in vivo, HEC gels will be more susceptible than Na CMC gels to alterations in these rheological properties. Consequently, it would be expected that the clinical performance of HEC gels will be modified to a greater extent than Na CMC gels. In general, HEC gels exhibited a greater elastic nature than Na CMC gels over the frequency range employed for oscillation The storage and loss moduli and dynamic viscosity of both gel types increased, yet the loss tangent of both gel types decreased as a function of increasing polymer concentration. Gel mucoadhesive strength was dependent on both the time of contact of the formulation with mucin and also on polymer concentration. In conclusion, this study has characterised a number of gels containing either HEC or Na CMC in terms of their mechanical/textural, viscoelastic and mucoadhesive properties. Due to its relevance to the clinical performance, it is suggested that the information derived from these methods may be usefully combined to provide a more rational basis for the selection of polymers and their formulation as topical drug delivery systems. (C) 1997 Elsevier Science B.V.

Textural analysis and flow rheometry of novel, bioadhesive antimicrobial oral gels

Purpose. This study examined the rheological and textural characteristics (hardness, compressibilty, adhesiveness and cohesiveness) of bioadhesive oral gels containing the antimicrobial agent chlorhexidine.

Texture profile analysis of bioadhesive polymeric semisolids: Mechanical characterization and investigation of interactions between formulation components

This study reports the use of texture profile analysis (TPA) to mechanically characterize polymeric, pharmaceutical semisolids containing at least one bioadhesive polymer and to determine interactions between formulation components. The hardness, adhesiveness, force per unit time required for compression (compressibility), and elasticity of polymeric, pharmaceutical semisolids containing polycarbophil (1 or 5% w/w), polyvinylpyrrolidone (3 or 5% w/w), and hydroxyethylcellulose (3, 5, or 10% w/w) in phosphate buffer (pH 6.8) were determined using a texture analyzer in the TPA mode (compression depth 15 mm, compression rate 8 mm s(-1) 15 s delay period). Increasing concentrations of polycarbophil, poly vinylpyrrolidone, and hydroxyethylcellulose significantly increased product hardness, adhesiveness, and compressibility but decreased product elasticity. Statistically, interactions between polymeric formulation components were observed within the experimental design and were probably due to relative differences in the physical states of polyvinylpyrrolidone and polycarbophil in the formulations, i.e., dispersed/dissolved and unswollen/swollen, respectively. Increased product hardness and compressibility were possibly due to the effects of hydroxyethylcellulose, polyvinylpyrrolidone, and polycarbophil on the viscosity of the formulations. Increased adhesiveness was related to the concentration and, more importantly, to the physical state of polycarbophil. Decreased product elasticity was due to the increased semisolid nature of the product. TPA is a rapid, straightforward analytical technique that may be applied to the mechanical characterization of polymeric, pharmaceutical semisolids. It provides a convenient means to rapidly identify physicochemical interactions between formulation components. (C) 1996 John Wiley & Sons, Inc.

Development of liposome gel based formulations for intravaginal delivery of the recombinant HIV-1 envelope protein CN54gp140

Mucosally-administered vaccine strategies are widely investigated as a promising means of preventing HIV infection. This study describes the development of liposomal gel formulations, and novel lyophilised variants, comprising HIV-1 envelope glycoprotein, CN54gp140, encapsulated within neutral, positively charged or negatively charged liposomes. The CN54gp140 liposomes were evaluated for mean vesicle diameter, polydispersity, morphology, zeta potential and antigen encapsulation efficiency before being incorporated into hydroxyethyl cellulose (HEC) aqueous gel and subsequently lyophilised to produce a rod-shaped solid dosage form for practical vaginal application. The lyophilised liposome-HEC rods were evaluated for moisture content and redispersibility in simulated vaginal fluid. Since these rods are designed to revert to gel form following intravaginal application, mucoadhesive, mechanical (compressibility and hardness) and rheological properties of the reformed gels were evaluated. The liposomes exhibited good encapsulation efficiency and the gels demonstrated suitable mucoadhesive strength. The freeze-dried liposome-HEC formulations represent a novel formulation strategy that could offer potential as stable and practical dosage form.

Physicochemical characterisation of injectable polymeric gels for use in the treatment of periodontal disease

The physicochemical characteristics of the injectable polymeric gels for use in the treatment of periodontal disease were investigated. The hardness, compressibility, and mucoadhesive properties of the gel were determined using a TA-XT2 Texture analyzer. The effect of of polymer concentration on the various viscoelastic, textural, bioadhesive properties and drug release were also analyzed using multifactorial analysis of variance. It was found that increased polymer concentration significantly increased gel structure, reduced polymer chain mobility and subsequently decreased the swelling/erosion and diffusion properties of the gel networks.

Electrically-responsive anti-adherent hydrogels for photodynamic antimicrobial chemotherapy

The loading of the photosensitisers meso-Tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP), methylene blue (MB) and IMP with sodium dodecyl sulphate (SDS) into and release from hydrogels composed of the polyelectrolyte poly(methyl vinyl ether-co-maleic acid) crosslinked in a 2:1 ratio with PEG 10,000 were investigated as a potential rapid photodynamic antimicrobial chemotherapy (PACT) treatment for infected wounds using iontophoresis as a novel delivery method. Photosensitiser uptake was very high; (% TMP uptake; 95.53-96.72%) (% MB uptake; 90.58-93.26%) and was PMVE/MA concentration independent, whilst SDS severely limited TMP uptake (5.93-8.75%). Hydrogel hardness, compressibility and adhesiveness on the dermal surface of neonate porcine skin increased with PMVE/MA concentration and were significantly increased with SDS.

The ionic conductivities of the hydrogels increased with PMVE/MA concentration. Drug release was PMVE/MA concentration independent, except for drug release under iontophoteric conditions for MB and TMP (without SDS). In just 15 min, the mean% drug concentrations released of TMP, TMP (with SDS) and MB using an electric current ranged from 22.30 to 64.72 mu gml(-1), 6.37-4.59 mu gml(-1) and 11.73-36.57 mu gml(-1) respectively. These concentrations were in excess of those required to induce complete kill of clinical strains of meticillin-resistant Staphylococcus aureus and Burkholderia cepacia. Thus these results support our contention that the iontophoteric delivery of IMP and MB using anti-adherent, electrically-responsive, PEG-crosslinked PMVE/MA hydrogels are a potential option in the rapid PACT treatment of infected wounds. (c) 2012 Elsevier B.V. All rights reserved.

On the γ-ray emission of Type Ia supernovae

A multidimension, time-dependent Monte Carlo code is used to compute sample ?-ray spectra to explore whether unambiguous constraints could be obtained from ?-ray observations of Type Ia supernovae. Both spherical and aspherical geometries are considered and it is shown that moderate departures from sphericity can produce viewing-angle effects that are at least as significant as those caused by the variation of key parameters in 1D models. Thus, ?-ray data could, in principle, carry some geometrical information, and caution should be applied when discussing the value of ?-ray data based only on 1D explosion models. In light of the limited sensitivity of current ?-ray observatories, the computed theoretical spectra are studied to revisit the issue of whether useful constraints could be obtained for moderately nearby objects. The most useful ?-ray measurements are likely to be of the light curve and time-dependent hardness ratios, but sensitivity higher than currently available, particularly at relatively hard energies (~2-3 MeV), is desirable. © 2008 The Authors. Journal compilation © 2008 RAS.

The development of a surface defect machining method for hard turning processes

Hard turning (HT) is a material removal process employing a combination of a single point cutting tool and high speeds to machine hard ferrous alloys which exhibit hardness values over 45 HRC. In this paper, a surface defect machining (SDM) method for HT is proposed which harnesses the combined advantages of porosity machining and pulsed laser pre-treatment processing. From previous experimental work, this was shown to provide better controllability of the process and improved quality of the machined surface. While the experiments showed promising results, a comprehensive understanding of this new technique could only be achieved through a rigorous, in depth theoretical analysis. Therefore, an assessment of the SDM technique was carried out using both finite element method (FEM) and molecular dynamics (MD) simulations.
FEM modelling was used to compare the conventional HT of AISI 4340 steel (52 HRC) using an Al2O3 insert with the proposed SDM method. The simulations showed very good agreement with the previously published experimental results. Compared to conventional HT, SDM provided favourable machining outcomes, such as reduced shear plane angle, reduced average cutting forces, improved surface roughness, lower residual stresses on the machined surface, reduced tool–chip interface contact length and increased chip flow velocity. Furthermore, a scientific explanation of the improved surface finish was revealed using a state-of-the-art MD simulation model which suggested that during SDM, a combination of both the cutting action and rough polishing action help improve the machined surface finish.

Effect of post-weld-annealing on the tensile deformation characteristics of laser-welded NiTi thin foil

Laser welding is an important process for fabricating complex components involving NiTi shape memory
alloy. As welding is a thermal process, the amount of heat input and the rate of cooling have significant
impact on the microstructure and hence the resultant characteristics of NiTi. In this study, the effect of
laser welding and post-weld-annealing from 573 K to 1173 K on the thermal phase transformation behaviors,
tensile deformation and micro-hardness characteristics of the laser-welded NiTi thin foils were investigated.
It was found that the as-welded sample exhibited inferior super-elasticity compared to the base
material, and the super-elasticity could be partially restored by annealing at 573 K. On the other hand,
annealing of the weldment above the recrystallization temperature would lower the super-elasticity.

Parameter study on laser welding of nitinol wire by Taguchi method

A L27 Taguchi experiment was done to investigate the effect of laser power, welding time, laser mode (CW and two pulsed modes), focus position, and their possible interactions on the weld-bead aspect ratio of laser-welded NiTi wires by using a 100W fibre laser. The optimized parameter setting to produce the full penetrated weldment with minimum welding defects is successfully determined in the Taguchi experiment. The laser mode is found to be the most important parameter that directly controls the weld-bead aspect ratio. The focus position is the secondly important parameter for the laser welding of NiTi wires. Strong interaction between the power and focus position is found in the Taguchi experiment. The optimized weldment produced by the Taguchi experiment is mainly of columnar dendritic structure in the weld zone (WZ) with the size of 1-3µm, while the HAZ exhibits equiaxed grain structure with the size of 5-10µm. The Vickers micro-hardness test indicted that the WZ and HAZ in the weldment are softened to certain extends after fibre laser welding.

Effects of sintering temperature on morphology and mechanical characteristics of 3D printed porous titanium used as dental implant

Porous titanium samples were manufactured using the 3D printing and sintering method in order to determine the effects of final sintering temperature on morphology and mechanical properties. Cylindrical samples were printed and split into groups according to a final sintering temperature (FST). Irregular geometry samples were also printed and split into groups according to their FST. The cylindrical samples were used to determine part shrinkage, in compressive tests to provide stress-strain data, in microCT scans to provide internal morphology data and for optical microscopy to determine surface morphology. All of the samples were used in microhardness testing to establish the hardness. Below 1100 C FST, shrinkage was in the region of 20% but increased to approximately 30% by a FST of 1300 C. Porosity varied from a maximum of approximately 65% at the surface to the region of 30% internally. Between 97 and 99% of the internal porosity is interconnected. Average pore size varied between 24 µm at the surface and 19 µm internally. Sample hardness increased to in excess of 300 HV0.05 with increasing FST while samples with an FST of below 1250 C produced an elastic-brittle stress/strain curve and samples above this displayed elastic-plastic behaviour. Yield strength increased significantly through the range of sintering temperatures while the Young's modulus remained fairly consistent. © 2013 Elsevier B.V.

Parameter Optimization on Laser Welding of NiTi Wires by Taguchi Method

In this research, a preliminary study was done to find out the initial parameter window to obtain the full-penetrated NiTi weldment. A L27 Taguchi experiment was then carried out to statistically study the effects of the welding parameters and their possible interactions on the weld bead aspect ratio (or penetration over fuse-zone width ratio), and to determine the optimized parameter settings to produce the full-penetrated weldment with desirable aspect ratio. From the statistical results in the Taguchi experiment, the laser mode was found to be the most important factor that substantially affects the aspect ratio. Strong interaction between the power and focus position was found in the Taguchi experiment. The optimized weldment was mainly of columnar dendritic structure in the weld zone (WZ), while the HAZ exhibited equiaxed grain structure. The XRD and DSC results showed that the WZ remained the B2 austenite structure without any precipitates, but with a significant decrease of phase transformation temperatures. The results in the micro-hardness and tensile tests indicated that the mechanical properties of NiTi were decreased to a certain extent after fibre laser welding.

Diamond machining of silicon: A review of advances in molecular dynamics simulation

Molecular dynamics (MD) simulation has enhanced our understanding about ductile-regime machining of brittle materials such as silicon and germanium. In particular, MD simulation has helped understand the occurrence of brittle–ductile transition due to the high-pressure phase transformation (HPPT), which induces Herzfeld–Mott transition. In this paper, relevant MD simulation studies in conjunction with experimental studies are reviewed with a focus on (i) the importance of machining variables: undeformed chip thickness, feed rate, depth of cut, geometry of the cutting tool in influencing the state of the deviatoric stresses to cause HPPT in silicon, (ii) the influence of material properties: role of fracture toughness and hardness, crystal structure and anisotropy of the material, and (iii) phenomenological understanding of the wear of diamond cutting tools, which are all non-trivial for cost-effective manufacturing of silicon. The ongoing developmental work on potential energy functions is reviewed to identify opportunities for overcoming the current limitations of MD simulations. Potential research areas relating to how MD simulation might help improve existing manufacturing technologies are identified which may be of particular interest to early stage researchers.

Enhancement of the properties of EPDM/NBR elastomers using nanoclay for seal applications

In this research, we have investigated the effects of addition of different percentages of nanoclay to the ethylene propylene diene monomer (EPDM) and nitrile butadiene rubber (NBR) on the characteristics of these rubbers as seal material. Properties such as tensile strength, modulus at different extensions, elongation at break, compressive set, hardness, and permeability and abrasion resistance are tested to assess the effect of addition of the nanoclay. Results indicate that addition of nanoclay at certain compositions could slightly reduce the strength of the rubber. However more stable modulus at different strains are provided, the hardness of the rubber is preserved and slightly enhanced, the permeability is reduced in both rubbers especially considerable decrease in EPDM is observed which is desirable in diminishing the effect of explosive decompression. At the same time the compression test shows that the nanoclay improves the performance of the rubbers under compression which is essential in seal application. The X-ray diffraction tests clarify that the dispersion of the nanoclay in the NBR samples is of high quality. In the EPDM samples, the dispersion is in need of improvement. POLYM. COMPOS., 30:1657-1667, 2009. © 2008 Society of Plastics Engineers.