Sie Huey Lee

Nano spray drying: a novel method for preparing protein nanoparticles for protein therapy.

There has been an increasing interest in the development of protein nanotherapeutics for diseases such as cancer, diabetes and asthma. Spray drying with prior micro mixing is commonly used to obtain these powders. However, the separation and collection of protein nanoparticles with conventional spray dryer setups has been known to be extremely challenging due to its typical low collection efficiency for fine particles less than 2μm. To date, there has been no feasible approach to produce these protein nanoparticles in a single step and with high yield (>70%). In this study, we explored the feasibility of the novel Nano Spray Dryer B-90 (equipped with a vibrating mesh spray technology and an electrostatic particle collector) for the production of bovine serum albumin (BSA) nanoparticles. A statistical experimental design method (Taguchi method based on three levels, five variables L(18) orthogonal array robust design) was implemented to study the effect of and optimize the experimental conditions of: (1) spray mesh size, (2) BSA solution concentration, (3) surfactant concentration, (4) drying air flow rate and (5) inlet temperature on: (1) size and (2) morphology (axial ratio). Particle size and morphology were predominantly influenced by the spray mesh size and surfactant concentration, respectively. The drying air flow rate and inlet temperature had minimal impact. Optimized production of smooth spherical nanoparticles (median size: 460±10nm, axial ratio: 1.03±0.00, span 1.03±0.03, yield: 72±4%) was achieved using the 4μm spray mesh at BSA concentration of 0.1% (w/v), surfactant concentration of 0.05% (w/v), drying flow rate of 150L/min and inlet temperature of 120°C. The Nano Spray Dryer B-90 thus offers a new, simple and alternative approach for the production of protein nanoparticles suited for a variety of drug delivery applications.

The nano spray dryer B-90

Introduction: Spray drying is an extremely well-established technology for the production of micro-particulate powders suited for a variety of drug delivery applications. In recent years, the rise in nanomedicine has placed increased pressure on the existing systems to produce nanoparticles in good yield and with a narrow size distribution. However, the separation and collection of nanoparticles with conventional spray dryer set ups is extremely challenging due to their typical low collection efficiency for fine particles < 2 μm. Currently, nanoparticles have to be agglomerated into larger microparticles, via a two-step approach, in order to collect them in a sizeable amount. However, this method has to contend with the issue of adequate redispersibility of the primary particles to reap the full benefits of nanosizing. Areas covered: An overview on the advances in spray drying technology is provided in this review with particular emphasis on the novel Buchi Nano Spray Dryer B-90. Readers will appreciate the limitations of conventional spray drying technology, understand the mechanisms of the Buchi Nano Spray Dryer B-90, and also learn about the strengths and shortcomings of the system. Expert opinion: The Buchi Nano Spray Dryer B-90 offers a new, simple and alternative approach for the production of nanoparticles suited for a variety of drug delivery applications.

Synergistic combination dry powders for inhaled antimicrobial therapy: formulation, characterization and in vitro evaluation.

In combination antimicrobial therapy, the desired outcome is to broaden the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may also emerge from such combinations, leading to treatment failure with serious consequences. It is therefore imperative to screen the drug candidates for compatibility and possible antagonistic interactions. The aim of this work was to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary (ciprofloxacin hydrochloride and gatifloxacin hydrochloride, SD-CIP/GAT) and ternary (ciprofloxacin hydrochloride, gatifloxacin hydrochloride, and lysozyme, SD-CIP/GAT/LYS) combinations were prepared via spray-drying on a BUCHI® Nano Spray Dryer B-90. The powder morphologies were spherical with a slightly corrugated surface and all within the respirable size range. The powders yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® at 60 L/min. Time-kill studies carried out against the respiratory tract infection-causing bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia, and Acinetobacter baumannii at 1 × the minimum inhibitory concentration (MIC) over 24h revealed no antagonistic behavior for both the binary and ternary combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the dual combination (SD-CIP/GAT) when it was tested against P. aeruginosa bacteria.

A novel inhaled multi-pronged attack against respiratory bacteria.

Airway mucus hypersecretion is a common clinical feature of many severe respiratory diseases, and when complicated by a recalcitrant bacterial infection, the whole treatment regimen thereby becomes more challenging and protracted. The accumulation of thickened mucus secretions in the lower airways provides a nutrient-rich breeding ground for bacteria that promotes their growth and limits the ease of effective eradication. Unfortunately, no direct-inhaled dry powder formulation to treat these respiratory mucoid infections more effectively is available commercially. This work therefore seeks to develop a highly-efficacious ternary dry powder inhaler (DPI) formulation (ciprofloxacin hydrochloride (CIP), gatifloxacin hydrochloride (GAT) and ambroxol hydrochloride (AMB)) capable of delivering a novel multi-pronged attack (synergy, quorum quenching and mucociliary clearance) on Pseudomonas aeruginosa, a common respiratory bacteria found in mucoid infections. The powders were prepared via spray drying, evaluated on their aerosol performance via a multi-stage liquid impinger (MSLI) and tested for their efficacies in bacteria-spiked artificial sputum medium (ASM). The optimized particles were of respirable-size (d50 of ∼1.61±0.03μm) and slightly corrugated. When dispersed via an Aerolizer® inhaler at 60L/min, the powder showed concomitant in vitro deposition, minimal capsule, device and throat retention, and highly promising and uniform fine particle fractions (of the loaded dose) of ∼64-69%, which was a vast improvement over the singly-delivered actives. Favourably, when tested on bacteria-spiked ASM, the optimized ternary formulation (with AMB) was more effective at killing bacteria (i.e. faster rate of killing) than just the synergistic antibiotics alone (binary formulation; without AMB). In conclusion, a ternary antibiotic-(non-antibiotic) DPI formulation involving a unique multi-pronged attack mechanism was successfully pioneered and optimized for mucoid infections.

Steroid-Decorated Antibiotic Microparticles for Inhaled Anti-Infective Therapy

Despite advances in vaccination and antimicrobial therapy, community-acquired pneumonia (CAP) remains as a leading cause of morbidity and mortality worldwide. As the severity of CAP has been linked to the extent of inflammation in the body, adjunctive therapeutic measures aimed at modulating the immune response have therefore become increasingly attractive in recent years. In particular, for CAP patients with underlying medical conditions such as chronic obstructive pulmonary disease (COPD), a steroid-antibiotic combination will no doubt be a useful and timely therapeutic intervention. Unfortunately, no combined steroid-antibiotic dry powder formulation is available commercially or has been reported in the academic literature. The aim of this work was hence to develop a novel steroid-antibiotic dry powder inhaler formulation [ciprofloxacin hydrochloride (CIP) and beclomethasone dipropionate (BP)] for inhaled anti-infective therapy. The spray-dried powder was of respirable size (d50 of ∼2.3 μm), partially crystalline and had BP preferentially deposited on the particle surface. Favorably, when formulated as a binary mix, both CIP and BP showed much higher drug release and fine particle fractions (of the loaded dose) over their singly delivered counterparts, and had robust activity against the respiratory tract infection-causing bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.

Synergistic combination dry powders for inhaled antimicrobial therapy

Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI® Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® DPI at...

Visualizing powder de-agglomeration upon impact with simultaneous flowing charge behaviour

The effectiveness of the dry powder inhaler (DPI) in treating respiratory diseases lies in its ability to deliver consistent and reliable drug dosage with each actuation. From aerosolization upon actuation to throat impaction, the deagglomeration with subsequent detachment of the drug from the carrier particles depend on the interaction forces, including electrostatic contributions, between the particles themselves or with the inhaler wall and the extent of which could depend on the surface roughness of the carrier particles. In this study, we have simultaneously investigated the contributions of the electrostatic forces while visualizing the de-agglomeration and impaction behaviours of carrier powders in an impaction throat model using a non-contact vibrating capacitive probe and a high speed camera respectively. Rough and smooth carrier particles were obtained by spray drying and then aerosolized at 60 L/min in the model. Higher flowing charges were observed for the rough aerosolized carrier particles w...