Electrospinning/electrospraying coatings for metal microneedles: A design of experiments (DOE) and quality by design (QbD) approach.

The research presented here shows QbD implementation for the optimisation of the key process parameters in electrohydrodynamic atomisation (EHDA). Here, the electrosprayed nanoparticles and electrospun fibers consisting of a polymeric matrix and dye. Eight formulations were assessed consisting of 5% w/v of polycaprolactone (PCL) in dichloromethane (DCM) and 5% w/v polyvinylpyrrolidone (PVP) in ethanol. A full factorial DOE was used to assess the various parameters (applied voltage, deposition distance, flow rate). Further particle and fiber analysis using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared Spectroscopy (FTIR), particle/fiber size distribution. In addition to this in vitro release studied were carried out using fluorescein and Rhodamine B as model dyes and in vitro permeation studies were applied. The results show a significant difference in the morphology of resultant structures as well as a more rapid release profile for the PVP particles and fibers in comparison to the sustained release profiles found with PCL. In vitro drug release studies showed 100% drug release after 7 days for PCL particles and showed 100% drug release within 120 min for PVP particles. The release kinetics and the permeation study showed that the MN successfully pierced the membrane and the electrospun MN coating released a large amount of the loaded drug within 6 h. This study has demonstrated the capability of these robust MNs to encapsulate a diverse range drugs within a polymeric matrix giving rise to the potential of developed personalised medical devices.

A New Polysulfone Membrane Dialyzer, NV, with Low-Fouling and Antithrombotic Properties.

BACKGROUND: The biggest problem in routine hemodialysis therapy is possibly the blood pressure fall experienced by patients during dialysis. In contrast, in medium- and long-term hemodialysis therapy, the main problem might be deterioration of arteriosclerosis because of medial calcification associated with dialysis vintage. Both problems are caused by an autonomic imbalance or structural change in the blood vessels. Inflammation due to extracorporeal blood circulation is another possible cause. This inflammation is considered to cause platelets activated by contact and adherence with the membrane surface to aggregate with white blood cells and attack the endothelium of the blood vessels. Therefore, we tried to develop a new membrane with no adsorption and no platelet activation. SUMMARY: Polysulfone (PS) membranes with polyvinylpyrrolidone (PVP) as a hydrophilic agent are widely used in dialysis, but blood components adhere to the membrane surface. We developed a new dialyzer, NV, by localizing a new hydrophilic polymer onto the inner surface of a hollow-fiber membrane composed of PS and PVP. The number of platelets that adhered to the NV membrane surface drastically decreased to 0.9% of that with the conventional PS dialysis membrane. We also confirmed the mechanism by which NV realizes clinical improvements in blood pressure drops and inflammation during dialysis, and verified its clinical appeal. Key Messages: The new membrane NV, which inhibits platelet adhesion and is compatible with blood vessels, is clinically beneficial.

PVP- coated naringenin nanoparticles for biomedical applications - In vivo toxicological evaluations.

Naringenin (NAR) is one of the naturally occurring flavonoids found in citrus fruits and exerts a wide variety of pharmacological activities. The clinical relevance of naringenin is limited by its low solubility and minimal bioavailability, owing to its largely hydrophobic ring structure. The aim of the present study is to develop a novel naringenin nanoparticle system (NAR NP) using simple nanoprecipitation technique with polyvinylpyrrolidone (PVP) as the hydrophilic carrier. The synthesized nanoparticles were characterized using XRD, FTIR, SEM and EDX. The characterization study revealed the nanoscale properties and the interactions between NAR and PVP. In vivo toxicological evaluations were carried out at various doses (1, 5, 10 & 50 mg/kg body wt) in male Sprague-Dawley rats in comparison with silver nanoparticle (AgNP) at toxic concentration (50 mg/kg body wt). The altered hepatotoxicity markers, hematology parameters and antioxidant defense system were observed in AgNP- treated rats. But NAR NP - treated rats did not show any biochemical alterations and improved the antioxidant defense indices when compared to control group, by virtue of the pharmacological properties exerted by NAR. The modulatory effect of NAR NP over inflammatory and stress signaling cascades were confirmed by the normalized mRNA expressions of NF-κB, TNF-α and IL-6. The histopathological analysis of liver, kidney and heart reinforce our findings. These studies provide preliminary answers to some of the key biological issues raised over the use and safety of nanoparticles for diagnostic and therapeutic applications. Consequently, we suggest that the safe NAR NP can be used to reduce the dosage of NAR, improve its bioavailability and merits further investigation for therapeutic applications.

Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets.

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect their processability and several critical quality attributes of the resulting granules and tablets.

Assessment of disinfectants cleaning against bacterial biofilm of house hold water tanks.

UNLABELLED: The purpose of this study was to compare the efficacy, in terms of bacterial biofilm penetration and killing, of some chemical disinfectants against E. coli and P. aeruginosa. This study was undertaken to examine the efficacy of some disinfectants including sodium hypochlorite, povidine and tryad detergent against E. coli biofilms and the efficacy of sodium hypochlorite and tryad detergents against P. aeruginosa. Two species biofilm of E. coli and P. aeruginosa were grown by flowing a dilute tryptic soy broth medium over an inclined cement, polyethylene, fiberglass and galvanized steel slides, 2.25 x 2.25 cm2 for 15 days. Biofilm formation was evaluated by scanning electron microscopy (SEM) and standard plate counts procedures through selective media for both E. coli and P. aeruginosa. In addition, some disinfectants were selected through disk diffusion susceptibility test. The disinfectants which gave higher zone of inhibitions, were applied to remove of E. coli and P. aeruginosa biofilms from cement, fiberglass, polyethylene and galvanized steel slide surfaces. Results showed that all disinfectants tested gave high inhibition of biofilm adhesion to tank surfaces with some being significant. CONCLUSION: polyethylene and galvanized steel are strongly recommended as alternative drinking house holds water tanks in Saudi Arabia. The choice of disinfectants or cleaning agents along with optimum concentrations and the time of action is very important when destroying microbes. It is also important that resistance of microbes to some disinfectants and cleaning agents is take into consideration when planning the cleaning process.

Evaluation of the functional equivalence of crospovidone NF from different sources. II. Standard performance test.

Current NF monographs do not provide tests that reflect on the functionality of Crospovidone NF from multiple sources. Physical characterization studies such as particle size and distribution, surface area, porosity, and surface morphology revealed major differences among the crospovidones from different sources (Shah, U.; Augsburger, L.L. J. Pharm. Dev. Technol. 2001, 6 (1), 39-51). Differences in disintegration and dissolution were also observed for a model drug in an insoluble filler system (see Shah and Augsburger, 2001). The objective of this study was to determine the relationship between physical differences observed and disintegrant functionality and to develop standard performance test. Tests performed included settling volume studies, measurement of initial rate as well as extent of liquid uptake of the loose disintegrant powder, and simultaneous measurement of the axial and radial disintegrating forces along with the rate and extent of liquid uptake of the pure disintegrant compacts. Significant differences among the crospovidones were observed for all tests performed. Settling volume, liquid uptake, and disintegration force are recommended as standard performance tests to determine differences among crospovidones from different sources.

Comparison of cryoprotectants in the preservation of Theileria parva sporozoites using an in vitro infectivity assay.

An in vitro infectivity assay was used to examine five cryoprotectants for their suitability for preserving Theileria parva sporozoites. All five were capable of preserving T. parva sporozoites through freezing, the optimal concentrations being 7.5% for glycerol, 5% for dimethyl sulphoxide (DMSO), poly (vinylpyrrolidone) (PVP) and poly(ethylene glycol) (PEG), and 2.5% for hydroxyethyl starch (HES). When the five cryoprotectants were compared at their optimal concentrations, using a modification of the standard method of stabilate preparation, glycerol was significantly better than the others (p < 0.05). Measurement of the effects of each cryoprotectant on the osmolality of the media revealed that glycerol and DMSO elevated the osmolality significantly (p < 0.05). Resuscitation of glycerol-preserved sporozoites required the presence of glycerol in the diluent to maintain infectivity. Studies on the effects of equilibration time in glycerol on the infectivity of sporozoites showed that those frozen immediately after mixing (2 min) were as infective as those frozen after 60 min of equilibration.

[Problems of development, production and clinical use of highly effective blood substitutes]. / Problemy razrabotki, proizvodstva i klinicheskogo primeneniia vysokoéffektivnykh krovezamenitelei.

An analysis of biological properties of blood substitutes has shown the expedience of wider clinical use instead of polyglucin of such substitutes as polyglucol, polifer, rondex, neorondex, polyoxidin, volecam; instead of rheopolyglucin--the rheopolyglucin with glucose, rheogluman and rheoglusol prepared for clinical tests; instead of haemodesin--haemodesin-H, neohaemodesin, gluconeodesin; instead of protein hydrolysates--polyamine and purified from peptides infusamine, hydromine, amicin; instead of 0.9% solution of sodium chloride--disol, quintasol, lactasol, mafusol. They have polyfunctional properties and considerably increase the effectiveness of the infusion--transfusion therapy.

Is Percoll safe for in vivo use?

Fourteen virgin female rabbits were injected with 60% Percoll solution in the right ovary and uterine horn and sperm prepared with Percoll in the left ovary and uterine horn. Histologic examination after 4 weeks showed no inflammatory cell infiltration in either uterine horns or ovaries.

Fluress, fluorescein and benoxinate: recovery from bacterial contamination.

The ability to recover from bacterial contaminations with Staphylococcus auresus and Pseudomonas aeruginosa was determined for three optometric DPAs: Fluress, fluorescein and benoxinate. Results show that Fluress recovers from contamination more rapidly than benoxinate or fluorescein. This ability to recover from contamination and the relative ease of use of Fluress may make it the DPA choice for a number of optometric procedures including applanation tonometry.