Particle aerosolisation and break-up in dry powder inhalers: evaluation and modelling of impaction effects for agglomerated systems.

This study utilised a combination of computational fluid dynamics (CFD) and standardised entrainment tubes to investigate the influence of impaction on the break-up and aerosol performance of a model inhalation formulation. A series of entrainment tubes, with different impaction plate angles were designed in silico and the flow characteristics, and particle tracks, were simulated using CFD. The apparatuses were constructed using three-dimensional printing.

Mannitol delivery by vibrating mesh nebulisation for enhancing mucociliary clearance.

Mucociliary clearance is compromised by airway surface liquid dehydration in respiratory disease states such as cystic fibrosis. Rehydration by hyperosmolar agents such as nebulised hypertonic saline and dry powder mannitol has demonstrated in vivo safety and efficacy for restoring mucociliary function. Mannitol, delivered as a nebulised formulation for this purpose, has not been investigated as yet.

Parameters affecting drug release from inert matrices. 1: Monte Carlo simulation.

This study investigates the use of Monte Carlo simulation for the determination of release properties from cubic inert matrices. Specifically, the study has focused on factors including porosity, surface area and tortuosity. The release platform was formed by simulating matrices with different ratios of drug and excipient, which undergo drug release in a uni-directional (two-face) or omni-directional (six-face) process.

CT and MR imaging of the mitral valve: radiologic-pathologic correlation.

Computed tomography (CT) and magnetic resonance (MR) imaging are increasingly important adjuncts to echocardiography for the evaluation of mitral valve disease. The mitral valve may be involved in various acquired or congenital conditions with resultant regurgitation or stenosis, and many of these conditions can be identified with CT or MR imaging. In addition, CT is useful for detecting and monitoring postoperative complications after mitral valve repair or replacement.

Respiratory navigated free breathing 3D spoiled gradient-recalled echo sequence for contrast-enhanced examination of the liver: diagnostic utility and comparison with free breathing and breath-hold conventional examinations.

Objective: The purpose of our study was to evaluate image quality in a 3D spoiled gradient-recalled echo (SPGR) sequence that was modified to incorporate respiratory navigation to limit the deleterious effects of respiratory motion and to compare it with conventional scanning during breath-holding and free breathing.

Conclusion: Respiratory navigation of 3D SPGR sequences is technically feasible, and image quality is modestly improved over free breathing acquisitions using conventional 3D SPGR sequences. This may represent a promising imaging alternative for patients who cannot hold their breath.

Max CAPR: high-resolution 3D contrast-enhanced MR angiography with acquisition times under 5 seconds.

High temporal and spatial resolution is desired in imaging of vascular abnormalities having short arterial-to-venous transit times. Methods that exploit temporal correlation to reduce the observed frame time demonstrate temporal blurring, obfuscating bolus dynamics. Previously, a Cartesian acquisition with projection reconstruction-like (CAPR) sampling method has been demonstrated for three-dimensional contrast-enhanced angiographic imaging of the lower legs using two-dimensional sensitivity-encoding acceleration and partial Fourier acceleration, providing 1mm isotropic resolution of the calves, with 4.

Artesunate-clindamycin multi-kinetics and site-specific oral delivery system for antimalaric combination products.

The aim of this work was to study a multi-kinetics and site-specific oral antimalaria drug delivery system (MKS_DDS), containing artesunate and clindamycin, based on the Dome Matrix module assembly technology. The MKS_DDS assembled system comprises of four modules, i.e.

Radiation dose reduction in CT coronary angiography.

During recent years, technologic advancements in computed tomography (CT) have allowed robust cardiac and coronary imaging. Small, mobile cardiac structures such as the coronary arteries can now be imaged directly and noninvasively with high precision. Given the fact that coronary CT angiography (CCTA) can detect preclinical calcified and noncalcified atherosclerosis, there is potential to revolutionize the management of ischemic heart disease by refining risk stratification and improving outcomes in various clinical settings.

Time- and passage-dependent characteristics of a Calu-3 respiratory epithelial cell model.

Background: Although standard protocols for the study of drug delivery in the upper airways using the sub-bronchial epithelial cell line Calu-3 model, particularly that of the air-liquid interface configuration, are readily available, the model remains un-validated with respect to culture conditions, barrier integrity, mucous secretion, and transporter function. With respect to the latter, the significance of functional P-glycoprotein (P-gp) activity in Calu-3 cells has recently been questioned, despite previous reports demonstrating a significant contribution by the same transporter in limiting drug uptake across the pulmonary epithelium. Therefore, the aim of this study was the standardization of this model as a tool for drug discovery.

Particle aerosolisation and break-up in dry powder inhalers 1: evaluation and modelling of venturi effects for agglomerated systems.

Purpose: This study utilized a combination of computational fluid dynamics (CFD) and standardized entrainment tubes to investigate the influence of turbulence on the break-up and aerosol performance of a model inhalation formulation.

Methods: Agglomerates (642.8 mum mean diameter) containing 3.

Co-spray-dried mannitol-ciprofloxacin dry powder inhaler formulation for cystic fibrosis and chronic obstructive pulmonary disease.

The aim of this study was to assess the potential of delivering a combination therapy, containing mannitol (a sugar alcohol with osmotic characteristics), and ciprofloxacin hydrochloride (an antibacterial fluoroquinolone), as a dry powder inhaler (DPI) formulation for inhalation. Single and combination powders were produced by spray drying ciprofloxacin and mannitol, from aqueous solution, at different ratios and under controlled conditions, as to obtain similar particle size distributions. Each formulation was characterised using laser diffraction, scanning electron microscopy, differential scanning calorimetry, dynamic vapour sorption, X-ray powder diffraction, and colloidal force microscopy.

The contribution of different formulation components on the aerosol charge in carrier-based dry powder inhaler systems.

Purpose: To measure aerosol performance of a lactose carrier/salbutamol sulphate powder blend and identify contributions of non-formulation and formulation components on the resulting aerosol charge.

Methods: A 67.5:1 (%w/w) blend of 63-90 microm lactose with salbutamol sulphate, and lactose alone (with and without the blending process), was dispersed from a Cyclohaler into the electrical Next Generation Impactor at 30, 60 and 90 L/min.

Image-guided placement of occipitocervical instrumentation using a reference arc attached to the headholder.

Objective: To develop a safe and accurate method of image-guided placement of instrumentation in the upper cervical spine and occiput in which the reference arc is fixed to the headholder.

Methods: The authors describe a technique for placing screws at the occipital, C1, and C2 levels using 3-dimensional image guidance in which the reference arc is fixed to the headholder. Technical details are discussed as well as modifications to the technique to maximize navigation accuracy and decrease the need for re-registration.

Does electrostatic charge affect powder aerosolisation?

To study if electrostatic charge initially present in mannitol powder plays a role in the generation of aerosols, mannitol was unipolarly charged to varying magnitudes by tumbling the powder inside containers of different materials. The resulting charge in the powder was consistent with predictions from the triboelectric charging theories, based on the work function values from literature and electron transfer tendencies from measurement of contact angle. The latter generated a parameter, gamma(-)/gamma+, which is a measure of the electron-donating capacity relative to the electron-accepting tendency of material.

Pharmacopeial methodologies for determining aerodynamic mass distributions of ultra-high dose inhaler medicines.

Three different impactor methodologies, the Andersen cascade impactor (ACI), next-generation impactor (NGI) and multistage-liquid impinger (MSLI) were studied to determine their performance when testing ultra-high dose dry powder formulations. Cumulative doses of spray-dried mannitol (Aridol) were delivered to each impactor at a flow rate of 60Lmin(-1) (up to a max dose of 800mg delivering 20 sequential 40mg capsules). In general, total drug collected in both the ACI and NGI falls below the range 85-115% of label claim criteria recommended by the United States of America Food and Drug Administration (FDA) at nominal mannitol doses exceeding 20mg and 200mg, respectively.

Solid lipid budesonide microparticles for controlled release inhalation therapy.

A solid lipid microparticle system containing budesonide was prepared by oil in water emulsification followed by spray drying. The solid lipid system was studied in terms of morphology, particle size distribution, crystallinity, thermal properties, aerosol performance, and dissolution/diffusion release. The microparticle system was also compared to conventional spray-dried crystalline and amorphous budesonide samples.

The influence of flow rate on the aerosol deposition profile and electrostatic charge of single and combination metered dose inhalers.

Purpose: The capability of the electrostatic next generation impactor (eNGI) has been investigated as a tool capable of measuring the electrostatic charge of single (Flixotide; containing fluticasone propionate (FP)) and combination (Seretide; FP and salmeterol xinafoate (SX)) pressurised metered dose inhalers (pMDIs) at different flow rates.

Methods: Aerosol mass distributions were investigated at 30, 60 and 90 l.min(-1) and simultaneous charge measurements recorded.

Imaging spectrum of bites, stings, and their complications: self-assessment module.

The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the imaging spectrum of bites, stings, and their complications.

Imaging spectrum of bites, stings, and their complications: pictorial review.

Objective: Soft-tissue injuries from animal bites and insect stings are frequent causes of emergency department visits. Although many cases follow a short and benign clinical course, life-threatening complications can occur. Imaging can play an important role in guiding clinical care by revealing the scope of the injury and associated complications.

Controlled release antibiotics for dry powder lung delivery.

Introduction: Two controlled release (CR) antibiotics intended for inhalation therapy were evaluated.

Material And Methods: Ciprofloxacin and doxycycline (both hydrochlorides) were selected as model drugs. Microparticles containing 90:10 ratio of polyvinyl alcohol (PVA) and single antibiotics or combinations were obtained via spray drying.

Delivery of antibiotics to the respiratory tract: an update.

The use of inhaled medications for the treatment of pulmonary diseases has become an increasingly popular drug delivery route over the past few decades. This delivery route allows for a drug to be delivered directly to the site of the disease, with a lower dose than more conventional oral or intravenous delivery methods, with reduced systemic absorption and consequently reduced risk of adverse effects. For asthma this delivery route has become the 'golden standard' of therapy.

Measuring charge and mass distributions in dry powder inhalers using the electrical Next Generation Impactor (eNGI).

The electrical Next Generation Impactor (eNGI) was assessed against the electrical low-pressure impactor (ELPI) and next generation impactor (NGI) for its capability to characterise particle size and electrostatic charge properties of dry powder inhaler (DPI) formulations. Following assessment, the relationship between inhalational air flow rate and drug powder charge was explored using the eNGI. At a vacuum flow rate of 30L/min, doses of Pulmicort (budesonide 400 microg) and Bricanyl (terbutaline 500 microg) were dispersed into the ELPI, NGI and eNGI, from which particle size profiles and charge profiles were ascertained.

Recent advances in controlled release pulmonary therapy.

Delivering therapeutic agents to the airways maximizes their concentration in lung tissue, decreasing systemic exposure or facilitating systemic absorption as desired. Many formulations exist for the treatment of respiratory illnesses however, no controlled release inhalation formulation exists to-date. This review is an update of the current advances in controlled release inhalation formulations and evaluation.

Force characterization of dielectrophoresis in droplet transport.

Transporting microdroplets using electric fields can be accomplished with several mechanisms, the primary methods being dielectrophoresis (DEP) for electrically insulating liquids, and electrowetting on dielectric for conducting fluids. In both cases, an electric field is applied near the leading edge of the droplet using patterned electrodes, giving rise to an electrostatic pressure that induces droplet transport. This paper examines the nature of the force distribution for DEP-actuated droplets in several electrode configurations, calculated using a numerical method designed for handling jump conditions in the Poisson equation.