Publications (116) View all
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Article: Nanotechnology Versus Other Techniques in Improving Drug Dissolution.
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ABSTRACT: Many newly discovered drug molecules have low aqueous solubility, which results in low bioavailability. One way to improve their dissolution is to formulate them as nanoparticles, which have high specific surface areas, consequently increasing the dissolution rate and solubility. Nanoparticles can be produced via top-down or bottom-up methods. Top-down techniques such as wet milling and high pressure homogenisation involve reducing large particles to nano-sizes. Some pharmaceutical products made by these processes have been marketed. Bottom-up methods such as precipitation and controlled droplet evaporation form nanoparticles from molecules in solution. To minimise aggregation upon drying and promote redispersion of the nanoparticles upon reconstitution or administration, hydrophilic matrix formers are added to the formulation. However, the nanoparticles will eventually agglomerate together after dispersing in the liquid and hinders dissolution. Currently there is no pharmacopoeial method specified for nanoparticles. Amongst the current dissolution apparatus available for powders, the flow-through cell has been shown to be the most suitable. Regulatory and pharmacopoeial standards should be established in the future to standardise the dissolution testing of nanoparticles. More nanoparticle formulations of new hydrophobic drugs are expected to be developed in the future with the advancement of nanotechnology. However, the agglomeration problem is inherent and difficult to overcome. Thus the benefit of dissolution enhancement often cannot be fully realised. On the other hand, chemical strategies such as modifying the parent drug molecule to form a more soluble salt form, prodrug, or cyclodextrin complexation are well established and have been shown to be effective in enhancing dissolution. Thus the value of nanoformulations needs to be interpreted in the light of their limitations. Chemical approaches should also be considered in new product development.Current pharmaceutical design 05/2013; · 4.41 Impact Factor -
Article: Effect of Device Design on the Aerosolization of a Carrier-Based Dry Powder Inhaler-a Case Study on Aerolizer(®) Foradile (®).
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ABSTRACT: The objective of this study is to investigate the effect of device design of the Aerolizer(®) on the aerosolization of a carrier-based dry powder inhaler formulation (Foradile(®)). The Aerolizer was modified by reducing the air inlet size and mouthpiece length to 1/3 of the original dimensions, or by increasing the grid voidage. Aerosolization of the powder formulation was assessed on a multi-stage liquid impinger at air flow rates of 30, 60, and 100 L/min. Coupled CFD-DEM simulations were performed to investigate the air flow pattern and particle impaction. There was no significant difference in the aerosolization behavior between the original and 1/3 mouthpiece length devices. Significant increases in FPF total and FPF emitted were demonstrated when the inlet size was reduced, and the results were explained by the increases in air velocity and turbulence from the CFD analysis. No significant differences were shown in FPF total and FPF emitted when the grid voidage was increased, but more drugs were found to deposit in induction port and to a lesser extent, the mouthpiece. This was supported by the CFD-DEM analysis which showed the particle-device collisions mainly occurred in the inhaler chamber, and the cross-grid design increased the particle-device collisions on both mouthpiece and induction port. The air inlet size and grid structure of the Aerolizer(®) were found to impact significantly on the aerosolization of the carrier-based powder.The AAPS Journal 02/2013; · 5.09 Impact Factor -
Article: Synergistic combination dry powders for inhaled antimicrobial therapy: Formulation, characterization and in vitro evaluation.
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ABSTRACT: 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 60L/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.European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 09/2012; · 3.15 Impact Factor -
Article: A novel dry powder inhalable formulation incorporating three first-line anti-tubercular antibiotics.
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ABSTRACT: Treatment for tuberculosis (TB) using the standard oral antibiotic regimen is effective but inefficient, requiring high drug dosing and lengthy treatment times. Three concurrent first-line antibiotics recommended by the World Health Organization (WHO) guidelines are pyrazinamide, rifampicin and isoniazid. Combining these antibiotics in a novel formulation for dry powder inhalation (DPI) may facilitate rapid and efficient resolution of local and systemic infection. However, spray-dried individually, these antibiotics were found to be physically unstable. A solution of the three antibiotics, at the WHO-recommended ratio, was spray-dried. The collected powder was assessed by a series of in vitro methods to investigate aerosol performance, particle physico-chemical characteristics and dissolution profile. Particles obtained were spherical with a surface composed primarily of rifampicin, as identified by TOF-SIMS. A mass median aerodynamic diameter of 3.5±0.1μm and fine particle fraction (<5μm) of 45±3% indicated excellent aerosol performance. The combination powder was differentiated by the presence of rifampicin dihydrate and the delta polymorph of pyrazinamide. Quantitative analysis indicated individual particles contained the three antibiotics at the expected proportions (400:150:75 w/w). This excipient-free triple antibiotic DPI formulation could be used as a significant enhanced treatment for TB.European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 09/2012; · 3.15 Impact Factor -
Article: Assessing the combinatorial influence of climate, formulation and device on powder aerosolization using the Taguchi experimental design
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ABSTRACT: In dry powder inhaler therapy, it is often highly desirable to maximise the fine particle fraction (FPF) while reducing the throat and inhaler retention. While there are a number of factors affecting aerosolization, there is at present no combinatorial study comparing the relative importance of each variable on dispersion and retention. In this work, the Taguchi experimental design, suitable for analysing a large number of factors and interactions within a reasonable number of runs, was applied to study the combinatorial effects of climate, air flow, carrier type and inhaler type on the aerosolization of micronized salbutamol sulphate as a model powder. Taguchi analysis revealed that FPF and throat deposition were highly dependent on the airflow rate and inhaler type, while device and capsule retention could be minimised via judicious selection of carrier and inhaler type respectively. The impact of dispersion climate (temperature and humidity) on aerosol penetration and retention was found to be of secondary importance. Analysis via the Taguchi experimental design thus represents a novel and useful approach for dissecting and understanding the large number of confounding variables affecting aerosolization.Powder Technology 04/2012; · 2.08 Impact Factor
