Paul M Young

Woolcock Institute of Medical Research, Sydney, New South Wales, Australia

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Publications (125)383.45 Total impact

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    ABSTRACT: This study investigated the effect of different active pharmaceutical ingredients (API) on aerosol electrostatic charges and aerosol performances for pressurized metered dose inhalers (pMDIs), using both insulating and conducting actuators. Five solution-based pMDIs containing different API ingredients including: beclomethasone dipropionate (BDP), budesonide (BUD), flunisolide (FS), salbutamol base (SB) and ipratropium bromide (IPBr) were prepared using pressure filling technique. Actuator blocks made from nylon, polytetrafluoroethylene (PTFE) and aluminium were manufactured with 0.3 mm nominal orifice diameter and cone nozzle shape. Aerosol electrostatics for each pMDI formulation and actuator were evaluated using the electrical low-pressure impactor (ELPI) and drug depositions were analysed using high performance liquid chromatography (HPLC). All three actuator materials showed the same net charge trend across the five active drug ingredients, with BDP, BUD and FS showing positive net charges for both nylon and PTFE actuators, respectively. While SB and IPBr had significantly negative net charges across the three different actuators, which correlates to the ionic functional groups present on the drug molecule structures. The API present in a pMDI has a dominant effect on the electrostatic properties of the formulation, overcoming the charge effect arising from the actuator materials. Results have shown that the electrostatic charges for a solution-based pMDI could be related to the interactions of the chemical ingredients and change in the work function for the overall formulation.
    Pharmaceutical Research 03/2015; 27(6). DOI:10.1007/s11095-015-1674-6 · 4.74 Impact Factor
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    ABSTRACT: The impact of a polyunsaturated fatty acid, arachidonic acid (AA), on membrane fluidity of epithelial cells and subsequent modulation of the drug transport was investigated. Membrane fluidity was assessed using molecular force microscopy. Calu-3 human bronchial epithelial cells were cultured on Transwell® inserts and the cell stiffness was assessed in the absence of fatty acids or in the presence of 30-μM AA. The morphology of the epithelial cells was distinctly different when AA was present, with the cell monolayer becoming more uniform. Furthermore the cell stiffness and variation in stiffness was lower in the presence of AA. In the fat-free medium, the median cell stiffness was 9.1kPa which dropped to 2.1kPa following exposure to AA. To further study this, transport of a common 2-agonist, salbutamol sulphate (SS) was measured in the presence of AA and in a fat free medium. The transport of SS was significantly higher when AA was present (0.61±0.09μg versus 0.11±0.003μg with and without AA respectively). It was evidenced that AA play a vital role in cell membrane fluidity and drug transport. This finding highlights the significance of the dietary fatty acids in transport and consequentially effectiveness of medications used to treat pulmonary diseases such as asthma.
    02/2015; DOI:10.1039/C4TB01928H
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    ABSTRACT: Ventilator-associated pneumonia (VAP) remains a major burden to the healthcare system and intubated patients in intensive care units. In fact, VAP is responsible for at least 50% of prescribed antibiotics to patients who need mechanical ventilation. One of the factors contributing to VAP pathogenesis is believed to be rapid colonization of biofilm-forming pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus on the surface of inserted endotracheal tubes. These biofilms serve as a protective environment for bacterial colonies and provide enhanced resistance towards many antibiotics. This review presents and discusses an overview of current strategies to inhibit the colonization and formation of biofilm on endotracheal tubes, including antibiotic treatment, surface modification and antimicrobial agent incorporation onto endotracheal tube materials.
    Expert Review of Anti-infective Therapy 01/2015; DOI:10.1586/14787210.2015.1007045 · 3.06 Impact Factor
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    ABSTRACT: The aim of this study was to assess the effects of low-dose clarithromycin, formulated as solution pressurized metered dose inhaler, following deposition on the Calu-3 respiratory epithelial cells. Clarithromycin was deposited on the air-interface culture of Calu-3 cells using a modified Andersen cascade impactor. Transport of fluorescein-Na, production of mucus and interleukin-8 release from Calu-3 cells following stimulation with transforming growth factor-β and treatment with clarithromycin was investigated. The deposition of clarithromycin had significant effect on the permeability of fluorescein-Na, suggesting that the barrier integrity was improved following a short-term treatment with clarithromycin (apparent permeability values were reduced to 3.57 × 10(-9) ± 2.32 × 10(-9) cm.s(-1), compared to 1.14 × 10(-8) ± 4.30 × 10(-8) cm.s(-1) for control). Furthermore, the amount of mucus produced was significantly reduced during the course of clarithromycin treatment. The concentration of interleukin-8 secreted from Calu-3 cells following stimulation with transforming growth factor-β resulted in significantly lower level of interleukin-8 released from the cells pre-treated with clarithromycin (5.2 ± 0.5 ng.ml(-1) clarithromycin treated vs. 7.7 ± 0.8 ng.ml(-1) control, respectively). Our data demonstrate that treatment with clarithromycin decreases the paracellular permeability of epithelial cells, mucus secretion and interleukin-8 release and therefore, inhaled clarithromycin holds potential as an anti-inflammatory therapy.
    Pharmaceutical Research 12/2014; DOI:10.1007/s11095-014-1605-y · 3.95 Impact Factor
  • Santo Scalia, Paul M Young, Daniela Traini
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    ABSTRACT: Introduction: Solid lipid particles were introduced in the early 1990s as an alternative drug carrier system to emulsions, liposomes and polymeric microparticles. Although lipid nanoparticles have been the object of a substantial number of reviews, fewer are available on lipid microparticles (LMs), despite their distinct advantages, including biocompatibility, ease of production and characterisation, extended release properties and high loading. Areas covered: This review presents an overview of the advantages and drawbacks of LMs, that is, lipid-based particles with dimensions in the micrometre range. Specific focus is on the role of the main excipients used for LM formulations, lipids and surfactants and their effects on LM properties. An update on preparation techniques and characterisation methods are also presented, with particular emphasis on more recent technologies. The interaction of LMs with biological systems and with cells in particular is reviewed. The various LM administration routes are examined, with special attention to most recent applications (i.e., pulmonary and nasal delivery). Expert opinion: LMs represent attractive and versatile carrier systems; however, their pharmaceutical applicability has been rather limited. Investigation on the use of LMs for less-established administration routes, such as pulmonary delivery, may provide further interest within the area of LM-based systems, both in industry and in the clinic.
    Expert Opinion on Drug Delivery 11/2014; DOI:10.1517/17425247.2015.980812 · 4.12 Impact Factor
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    ABSTRACT: A novel inhalable rifapentine dry powder formulation could improve pulmonary rifapentine concentrations to significantly shorten time to treat tuberculosis infection. The pharmacokinetics of rifapentine (20 mg/kg) in healthy mice was compared after intratracheal (IT) and intraperitoneal (IP) administration. Plasma, bronchoalveolar lavage (BAL) and tissue samples were harvested and drug quantified at time-points up to 24 hours. Concentration-time data were analysed using a mixed effects modelling approach to provide model-based estimates of area under the curve from time 0 to infinity (AUC0-∞). Between IT and IP delivery, the former had a considerably higher peak rifapentine lung and BAL concentration and associated AUC0-∞. The plasma AUC0-∞ after IT dry powder delivery was approximately 4-fold smaller than the IP value. Inhaled delivery of rifapentine has the potential to selectively enhance therapeutic efficacy at the pulmonary site of infection whilst minimising systemic exposure and related toxicity.
    International Journal of Antimicrobial Agents 11/2014; DOI:10.1016/j.ijantimicag.2014.11.009 · 4.26 Impact Factor
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    ABSTRACT: Purpose To investigate the influence of different actuator nozzle designs on aerosol electrostatic charges and aerosol performances for pressurised metered dose inhalers (pMDIs). Methods Four actuator nozzle designs (flat, curved flat, cone and curved cone) were manufactured using insulating thermoplastics (PET and PTFE) and conducting metal (aluminium) materials. Aerosol electrostatic profiles of solution pMDI formulations containing propellant HFA 134a with different ethanol concentration and/or model drug beclomethasone dipropionate (BDP) were studied using a modified electrical low-pressure impactor (ELPI) for all actuator designs and materials. The mass of the deposited drug was analysed using high performance liquid chromatography (HPLC). Results Both curved nozzle designs for insulating PET and PTFE actuators significantly influenced aerosol electrostatics and aerosol performance compared with conducting aluminium actuator, where reversed charge polarity and higher throat deposition were observed with pMDI formulation containing BDP. Results are likely due to the changes in plume geometry caused by the curved edge nozzle designs and the bipolar charging nature of insulating materials. Conclusions This study demonstrated that actuator nozzle designs could significantly influence the electrostatic charges profiles and aerosol drug deposition pattern of pMDI aerosols, especially when using insulating thermoplastic materials where bipolar charging is more dominant.
    Pharmaceutical Research 10/2014; 32(4). DOI:10.1007/s11095-014-1529-6 · 3.95 Impact Factor
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    ABSTRACT: Objectives: This study focuses on the development of a dry powder inhaler (DPI) formulation of simvastatin (SV), a common anti-cholesterol prodrug, which could potentially be used for its anti-inflammatory effects and its ability to reduce mucus production as therapy for respiratory diseases. Methods: Micronised SV samples were prepared by dry jet-milling. The longterm chemical stability and physicochemical properties of the formulations were characterised in terms of particles size, morphology, thermal and moisture responses. Furthermore, in vitro aerosol depositions were performed. The formulation was evaluated for cell viability and its effect on cilia beat activity, using ciliated nasal epithelial cells in vitro. The formulation transport across an established air interface Calu-3 bronchial epithelial cells and its ability to reduce mucus secretion was also investigated. Results: The particle size of the SV formulation and its aerosol performance were appropriate for inhalation therapy. Moreover, the formulation was found to be non-toxic to pulmonary epithelia cells and cilia beat activity up to a concentration of 10-6 M. Transport studies revealed that SV has the ability to penetrate into airway epithelial cells and is converted into its active SV hydroxy acid metabolite. Single dose of SV DPI also decreased mucus production after 4 days of dosing. Conclusion: This therapy could potentially be used for the local treatment of diseases like chronic obstructive pulmonary disease or cystic fibrosis, where hyper mucus production and inflammation are present.
    Expert Opinion on Drug Delivery 09/2014; DOI:10.1517/17425247.2015.963054 · 4.12 Impact Factor
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    ABSTRACT: Previous studies have suggested that particle-particle impaction may influence aerosolisation properties in carrier-based dry powder inhalers, through transfer of kinetic energy from large carriers to surface-deposited active drug. The importance of particle-particle collision has yet to be compared against other mechanisms that could lead to drug liberation, such as particle-wall impaction and turbulence. In particular, particle-particle collisions are difficult to model in silico due to computationalrestrictions. This study investigated the effects of dry powder inhaler particle-particle collisions in vitro using an established carrier-drug model dry powder inhalation formulation. Spherical polystyrene beads of median size 82.80 µmwere chosen as a model carrier as they were of uniform size, shape, surface area, density, porosity and hardness and thus eliminated potential variables that would have conflicted with the study. This model carrier was geometrically blended with micronised salbutamol sulphate(loaded blend).The correlation between the mass of loaded blend (5 - 40 mg) in the Rotahaler® DPI device and resulting fine particle fraction(FPF) was examined at a constant flow rate of 60 L.min-1. In a second experiment, the mass of loaded blend was kept constant and a variable amount of blank carrier particles were added to the Rotahaler® device to ascertain if additional "blank" carrier particles affected the final FPF.The efficiency of aerosolisation remained constant withvarying amounts of blank carrier particles as determined by the fine particle fraction of the emitted dose (FPFED)andfine particle fraction of the loadeddose (FPFLD). No statistical difference in FPFED and FPFLD values were observed for increasing masses of blank carrier. In addition, no statistical difference in FPFED and FPFLD between the two experiments was obtained. These observations suggest that particle-particle collisions are not a driving mechanism responsible for de-aggregation of drug from carrier-based systems.
    Current Drug Delivery 08/2014; · 2.25 Impact Factor
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    ABSTRACT: Endotracheal intubation is commonly associated with hospital-acquired infections as the intubation device acts as reservoir for bacterial colonization in the lungs. To reduce the incidence of bacterial colonization on the tubes, hydrogel coatings loaded with antimicrobial agents are gaining popularity. The aim of this study was to incorporate silver nanoparticles (AgNPs) into polyvinyl alcohol (PVA) to form stable hydrogels. Embedding AgNPs into PVA resulted in a decreased elongation at break and an increased tensile strength compared to PVA alone. The Ag release profile varied as a function of the degree of hydrolysis of PVA: the higher degree of hydrolysis demonstrated a lower release rate. Fourier infrared transform spectroscopy demonstrated that AgNPs interacted exclusively with the -OH groups of PVA. AgNP-loaded PVA was non-toxic against human normal bronchial epithelial cells while effective against the attachment of Pseudomonas aeruginosa and Staphylococcus aureus with a greater effect on P. aeruginosa.
    Biofouling 06/2014; 27(6):773-788. DOI:10.1080/08927014.2014.926475 · 3.70 Impact Factor
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    ABSTRACT: Non-volatile agents such as glycerol are being introduced into solution-based pMDI formulations in order to control mean precipitant droplet size. To assess their biopharmaceutical efficacy, both microscopic and macroscopic characteristics of the plume must be known, including the effects of external factors such as the flow generated by the patient's inhalation. We test the hypothesis that the macroscopic properties (e.g. spray geometry) of a pMDI spray can be predicted using a self-similarity model, avoiding the need for repeated testing.
    Pharmaceutical Research 06/2014; 31(11). DOI:10.1007/s11095-014-1391-6 · 3.95 Impact Factor
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    ABSTRACT: Introduction: Natural compounds are emerging as effective agents for the treatment of malignant diseases. Curcumin (diferuloylmethane), the active constituent of turmeric extract, has gained significant interest as a plant-based compound with anti-cancer properties. Curcumin is physiologically very well tolerated, with negligible systemic toxicity observed even after high oral doses administration. Despite curcumin's superior properties as an anti-cancer agent its applications are limited due to its low solubility and physico-chemical stability, rapid systemic clearance and low cellular uptake. Areas covered: This review focuses on the development of curcumin nano-particle formulation to improve its therapeutic index through enhanced cellular uptake, localization to targeted areas and improved bioavailability. The feasibility of nano-formulation in delivering curcumin and the limitations and challenges in designing and administrating the nano-sized curcumin particles are also covered in this review. Expert opinion: Nanotechnology is a promising tool to enhance efficacy and delivery of drugs. In this context, formulation of curcumin as nano-sized particles could reduce the required therapeutic dosages and subsequently reduced its cell toxicity. These nanoparticles are capable to provide local delivery of curcumin targeted to specific areas and thereby preventing systemic clearance. In addition, using specific coating, better pharmacokinetic and internalization of nano-curcumin could be achieved. However, the potential toxicity of nano-carriers for curcumin delivery is an important issue, which should be taken into account in curcumin nano-formulation.
    Expert Opinion on Drug Delivery 05/2014; DOI:10.1517/17425247.2014.916686 · 4.87 Impact Factor
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    ABSTRACT: Abstract A series of co-engineered macrolide-mannitol particles were successfully prepared using azithromycin (AZ) as a model drug. The formulation was designed to target local inflammation and bacterial colonization, via the macrolide component, while the mannitol acted as mucolytic and taste-masking agent. The engineered particles were evaluated in terms of their physico-chemical properties and aerosol performance when delivered via a novel high-payload dry powder Orbital(™) inhaler device that operates via multiple inhalation manoeuvres. All formulations prepared were of suitable size for inhalation drug delivery and contained a mixture of amorphous AZ with crystalline mannitol. A co-spray dried formulation containing 200 mg of 50:50 w/w AZ: mannitol had 57.6% ± 7.6% delivery efficiency with a fine particle fraction (≤6.8 µm) of the emitted aerosol cloud being 80.4% ± 1.1%, with minimal throat deposition (5.3 ± 0.9%). Subsequently, it can be concluded that the use of this device in combination with the co-engineered macrolide-mannitol therapy may provide a means of treating bronchiectasis.
    Drug Development and Industrial Pharmacy 05/2014; DOI:10.3109/03639045.2014.909841 · 2.01 Impact Factor
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    ABSTRACT: Simvastatin (SV), a drug of the statin class currently used orally as an anti-cholesterolemic via 10 the inhibition of the 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase, has been found 11 not only to reduce cholesterol but also to have several other pharmacological actions that might be 12 beneficial in airway inflammatory diseases. Currently, there is no inhalable formulation that could deliver 13 SV to the lungs. In this study, a pressurised metered-dose inhaler (pMDI) solution formulation of SV was 14 manufactured, with ethanol as a co-solvent, and its aerosol performance and physio-chemical properties 15 investigated. A pMDI solution formulation containing SV and 6%w/w ethanol was prepared. This 16 formulation was assessed visually for SV solubility. Furthermore, the aerosols performance (using 17 Andersen Cascade impactor at 28.3 L/min) and active ingredient chemical stability up to 6 months at 18 different storage temperatures, 4 and 25°C, were also evaluated. The physico-chemical properties of the 19 SV solution pMDI were also characterised by differential scanning calorimetry (DSC), thermogravimetric 20 analyses (TGA) and laser diffraction. The aerosol particles, determined using scanning electron micros-21 copy (SEM), presented a smooth surface morphology and were spherical in shape. The aerosol produced 22 had a fine particle fraction of 30.77±2.44% and a particle size distribution suitable for inhalation drug 23 delivery. Furthermore, the short-term chemical stability showed the formulation to be stable at 4°C for up 24 to 6 months, whilst at 25°C, the formulation was stable up to 3 months. In this study, a respirable and stable 25 SV solution pMDI formulation for inhalation has been presented that could potentially be used clinically 26 as an anti-inflammatory therapy for the treatment of several lung diseases. 27 28 KEY WORDS: lung inflammation; pMDI; pressurised metered dose inhaler; simvastatin. 29 30 INTRODUCTION 31 Statins (HMG-CoA reductase inhibitors) are widely used 32 as cholesterol-lowering drugs (1). These compounds inhibit 33 the activity of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-34 CoA) reductase enzyme, which catalyses the rate-limiting step 35 in mevalonate biosynthesis, a key intermediate in cholesterol 36 metabolism. Studies have recently described other possible 37 roles for statins as immuno-modulatory and anti-inflammatory 38 compounds, suggesting a protective mechanism of action (2– 39 5). Clinical studies have also shown that statins have been 40 found to be effective in decreasing cardiac events in persons 41 with average cholesterol levels and reduce inflammatory 42 markers (6–8). Furthermore, in vitro, animal and human stud-43 ies have found statin to have anti-inflammatory and mucolytic 44 actions (9–14). 45 Observational studies, via both retrospective and pro-46 spective analysis, have shown that statins may be useful in 47 reducing mortality rates in patients with chronic obstructive 48 pulmonary disease (COPD) (15–18). Furthermore, it has been 49 observed that, in a murine model of allergic asthma, statins 50 had an immune-modulatory effect through several different 51 anti-inflammatory pathways that still require further elucida-52 tion (19). In general, statins beneficial effects cannot entirely 53 be attributed to reduction of lipid levels (20,21). ABBREVIATIONS: ACI, Andersen Cascade Impactor; COPD, Chronic obstructive pulmonary disease; °C/min, Temperature degree per minute; DUSA, Dose uniformity apparatus; DSC, Differential scanning calorimetry; Dv 0.1 , 10% of the volume distribution is below this value; Dv 0.5 , The volume median diameter is the diameter where 50% of the distribution is above and 50% is below; Dv 0.9 , 90% of the volume distribution is below this value/0 # 2014 American Association of Pharmaceutical Scientists JrnlID 12249_ArtID 127_Proof# 1 -30/04/2014
    AAPS PharmSciTech 05/2014; 15(4):956. DOI:10.1208/s12249-014-0127-6 · 1.78 Impact Factor
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    ABSTRACT: Recent murine studies found that rifapentine, dosed daily, at least halved tuberculosis treatment times compared with standard rifampicin and isoniazid-containing regimens. However, in humans, an inhalable form of rifapentine may be necessary to considerably shorten treatment duration because of the physiological barriers associated with oral therapy. The current study compares two inhalable rifapentine dry powders-a novel pure crystalline form and an amorphous form-by a series of in vitro tests. The crystalline and amorphous powders had a mass median aerodynamic size of 1.68 ± 0.03 and 1.92 ± 0.01 μm, respectively, associated with a fine particle fraction of 83.2 ± 1.2% and 68.8 ± 2.1%, respectively. A quinone degradation product was identified in the amorphous powder stored for 1 month, whereas the crystalline form remained chemically stable after storage at both 0% and 60% relative humidity, 25°C, for at least 3 months. Solubilized rifapentine was well tolerated by pulmonary tissue and macrophage cells up to approximately 50 μM. The accumulation of rifapentine within alveolar macrophage cells was significantly higher than for rifampicin, indicating enhanced delivery to infected macrophages. The novel inhalable crystalline form of rifapentine is suitable for targeted treatment of tuberculosis infection and may radically shorten treatment duration. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 05/2014; 103(5). DOI:10.1002/jps.23911 · 3.13 Impact Factor
  • Jesslynn Ooi, Daniela Traini, Paul M Young
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    ABSTRACT: The production of high-quality graphical figures of scientific data is an important aspect of medical writing, since the significance of the research findings can be lost to the audience if the data are presented poorly or inaccurately. This review highlights the various requirements that a writer may encounter when preparing data in a graphical format for presentation and gives an overview of 15 graphing software packages that are available on a number of platforms.
    03/2014; 23(1):41-44. DOI:10.1179/2047480613Z.000000000185
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    ABSTRACT: This study focuses on the co-engineering of salbutamol sulphate (SS), a common bronchodilator, and mannitol (MA), a mucolytic, as a potential combination therapy for mucus hypersecretion. This combination was chosen to have a synergic effect on the airways: the SS will act on the β2-receptor for relaxation of smooth muscle and enhancement of ciliary beat frequency, whilst mannitol will improve the fluidity of mucus, consequently enhancing its clearance from the lung. A series of co-spray-dried samples, containing therapeutically relevant doses of SS and MA, were prepared. The physico-chemical characteristics of the formulations were evaluated in terms of size distribution, morphology, thermal and moisture response and aerosol performance. Additionally, the formulations were evaluated for their effects on cell viability and transport across air interface Calu-3 bronchial epithelial cells, contractibility effects on bronchial smooth muscle cells and cilia beat activity using ciliated nasal epithelial cells in vitro. The formulations demonstrated size distributions and aerosol performance suitable for inhalation therapy. Transport studies revealed that the MA component of the formulation enhanced penetration of SS across the complex mucus layer and the lung epithelia cells. Furthermore, the formulation in the ratios of SS 10(-6) and MA 10(-3) M gave a significant increase in cilia beat frequency whilst simultaneously preventing smooth muscle contraction associated with mannitol administration. These studies have established that co-spray dried combination formulations of MA and SS can be successfully prepared with limited toxicity, good aerosol performance and the ability to increase ciliary beat frequency for improving the mucociliary clearance in patients suffering from hyper-secretory diseases, whilst simultaneously acting on the underlying smooth muscle.
    The AAPS Journal 01/2014; 16(2). DOI:10.1208/s12248-014-9560-4 · 3.91 Impact Factor
  • Journal of Thermal Analysis and Calorimetry 01/2014; DOI:10.1007/s10973-014-3935-8 · 2.21 Impact Factor
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    ABSTRACT: The formulation of a clarithromycin (CLA) pressurised metered dose inhalers (pMDIs) solution formulation opens up exciting therapeutic opportunities for the treatment of inflammation in chronic obstructive lung diseases. In this study, we have formulated and tested a low dose macrolide formulation of CLA for treatment of inflammation and studied its physicochemical and aerosol properties. The system was characterised for in-vitro aerosol performance using an Andersen cascade impactor. Short-term chemical and physical stability was assessed by dose content uniformity over a range of temperatures. Standard physicochemical characteristics were also investigated using scanning electron microscopy, thermo analysis and laser diffraction techniques. The formulation had a relatively high fine particle fraction (47%) and produced a particle size distribution suitable for inhalation drug delivery. Particles had an irregular morphology and were predominately amorphous. Furthermore, the short-term stability showed the formulation to be stable from 4 to 37°C. This study demonstrated the feasibility of formulating a solution-based pMDI containing CLA for the treatment of lung inflammatory diseases.
    12/2013; 66(5). DOI:10.1111/jphp.12190
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    ABSTRACT: The purpose of this work was to evaluate gas perfusion isothermal calorimetry (ITC) as a method to characterize the physicochemical changes of active pharmaceutical ingredients (APIs) intended to be formulated in pressurised metered dose inhalers (pMDIs) after exposure to a model propellant. Spray dried samples of beclomethasone dipropionate (BDP) and salbutamol sulphate (SS) were exposed to controlled quantities of 2H,3H-decafluoropentane (HPFP) to determine whether ITC could be used as a suitable analytical method for gathering data on the behavioural properties of the powders in real time. The crystallization kinetics of BDP and the physiochemical properties of SS were successfully characterized using ITC and supported by a variety of other analytical techniques. Correlations between real and model propellant systems were also established using hydrofluoroalkane (HFA-227) propellant. In summary, ITC was found to be suitable for gathering data on the crystallization kinetics of BDP and SS. In a wider context, this work will have implications on the use of ITC for stability testing of APIs in HFA-based pMDIs.
    International Journal of Pharmaceutics 12/2013; DOI:10.1016/j.ijpharm.2013.11.055 · 3.99 Impact Factor

Publication Stats

1k Citations
383.45 Total Impact Points

Institutions

  • 2012–2015
    • Woolcock Institute of Medical Research
      Sydney, New South Wales, Australia
  • 2005–2015
    • University of Sydney
      • • Discipline of Pharmacology
      • • Faculty of Pharmacy
      • • Kolling Institute of Medical Research
      Sydney, New South Wales, Australia
  • 2003–2008
    • University of Bath
      • Department of Pharmacy and Pharmacology
      Bath, ENG, United Kingdom