Design and pharmaceutical applications of a low-flow-rate single-nozzle impactor.

A new low-flow-rate (0.5L/min) single-nozzle impactor for the concentration of dilute aerosol particles with selected pharmaceutical applications is described in this paper. The impactor can be configured up to 11 stages with a wide range of cutoff diameters from 0.6µm to 21.1µm, enabling convenient sampling of inhalable drug particles from inhalation devices and drug production processes. Its unique single-nozzle design and removable impaction plate allow direct sample transfer for subsequent compositional, morphological, solid-state, and other analysis. Agreement between the measured size distribution of fluticasone propionate particles actuated from commercial pMDI Flixotide® 250 Evohaler® and reported data in the literature verified that the impactor stages have accurate cutoff diameters as designed. The multi-stage configuration of the impactor allows rapid separation of polydisperse aerosol particles into different size classes for further characterization. Overlapping of the Raman spectra of the double-component powders from the Seretide® 250 pMDI collected using two different methods demonstrated the applicability of the impactor for a representative sampling of multi-component aerosol particles for bulk composition analysis. A time-dependent and size-dependent stability study was conducted consuming only a single sample canister with 80mg of amorphous indomethacin particles suspended in HFA-134a. It was found that amorphous indomethacin particles converted to the γ crystalline polymorph upon storage at 45°C and that the crystallization rate is strongly size dependent. With its highly effective aerosol collection capability and accurate cutoff diameters for aerosol classification, the impactor will have various applications in the pharmaceutical industry.

Humidity affects the morphology of particles emitted from beclomethasone dipropionate pressurized metered dose inhalers.

The effects of propellant type, cosolvent content, and air humidity on the morphology and solid phase of the particles produced from solution pressurized metered dose inhalers containing the corticosteroid beclomethasone dipropionate were investigated. The active ingredient was dissolved in the HFA propellants 134a and 227ea with varying levels of the cosolvent ethanol and filled into pressurized metered dose inhalers. Inhalers were actuated into an evaporation chamber under controlled temperature and humidity conditions and sampled using a single nozzle, single stage inertial impactor. Particle morphology was assessed qualitatively using field emission scanning electron microscopy and focused ion beam-helium ion microscopy. Drug solid phase was assessed using Raman microscopy. The relative humidity of the air during inhaler actuation was found to have a strong effect on the particle morphology, with solid spheroidal particles produced in dry air and highly porous particles produced at higher humidity levels. Air humidification was found to have no effect on the solid phase of the drug particles, which was predominantly amorphous for all tested formulations. A critical level of air relative humidity was required to generate porous particles for each tested formulation. This critical relative humidity was found to depend on the amount of ethanol used in the inhaler, but not on the type of propellant utilized. The results indicate that under the right circumstances water vapor saturation followed by nucleated water condensation or ice deposition occurs during particle formation from evaporating propellant-cosolvent-BDP droplets. This finding reveals the importance of condensed water or ice as a templating agent for porosity when particle formation occurs at saturated conditions, with possible implications on the pharmacokinetics of solution pMDIs and potential applications in particle engineering for drug delivery.

Drag Reduction Using Polysaccharides in a Taylor⁻Couette Flow.

Three different polysaccharides, aloe vera, Tamarind powder and pineapple fibers, are utilized as drag reducing agents in a turbulent flow. Using a Taylor⁻Couette setup, consisting of a rotating inner cylinder, for measuring the drag reduction, a range of Reynolds numbers from 4 × 104 to 3 × 105 has been explored in this study. The results are in good agreement with previous studies on polysaccharides conducted in a pipe/channel flow and a maximum drag reduction of 35% has been observed. Further, novel additives such as cellulose nanocrystals (CNC), surfactants and CNC grafted with surfactants are also examined in this study for drag reduction. CNC due to its rigid rod structure reduced the drag by 30%. Surfactant, due to its unique micelle formation showed maximum drag reduction of 80% at low Re. Further, surfactant was grafted on CNC and was examined for drag reduction. However, drag reduction property of surfactant was observed to be significantly reduced after grafting on CNC. The effect of Reynolds number on drag reduction is studied for all the additives investigated in this study.

Verapamil eluting stents as a possible treatment for vasospasm after subarachnoid hemorrhage.

OBJECTIVE: The only pharmacologic prophylaxis for cerebral vasospasm after subarachnoid hemorrhage is oral nimodipine. A novel way to mitigate this risk may be to design a drug eluting stent that elutes verapamil over the time period typically associated with vasospasm. In this study, we explore different methods of coating nitinol stents with a bioabsorbable polymer and determine the release profile of various verapamil coated stents for the potential treatment of vasospasm. METHODS: Nitinol stents were coated with different concentrations of poly(lactic acid-co-glycolic acid) (PLGA) in chloroform solution and using three coating techniques: dip coating, spin coating, and electrospinning. Morphology of the coatings were studied with scanning electron microscopy. 12 verapamil eluting stents were then prepared using different verapamil concentrations and coatings with different numbers of layers. Drug release behaviors were studied using UV spectroscopy for 21 days. RESULTS: Electrospinning at 20% w/v resulted in a smooth uniform coating without significant surface irregularities, and may be the most effective technique to coat stents. Stents with a single layer of PLGA/verapamil coating showed a two phase release profile (initial burst release followed by a slow rate of release) whereas stents with a bilayer coating showed a lower level of initial release followed by a slower sustained release phase. CONCLUSIONS: Development of verapamil eluting stents that elute drug over the time course typical of cerebral vasospasm, and for either immediate or prophylactic treatment, is technically feasible. Further in vitro and in vivo studies are required to determine whether this can improve the outcome of patients after subarachnoid hemorrhage.