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Nebulization
Published in Hans Bisgaard, Chris O’Callaghan, Gerald C. Smaldone, Drug Delivery to the Lung, 2001
Gerald C. Smaldone, Peter N. LeSouef
Using filters, the inhaled mass can be directly measured for a given patient; indeed, this technique can be expanded to measure the deposition of aerosol within the patient by comparing the amount inhaled versus the amount exhaled. The amount exhaled can be measured by filters on the expiratory line of the nebulizer (as shown in Fig. 4). In vivo filter measurements in patients can be cumbersome when different aerosol delivery devices are being screened in preclinical testing. Therefore, inhaled mass can be measured on the bench by substituting a mechanical ventilator for the patient (10). Figure 6 is a typical example. A piston pump (Harvard Pump, Harvard Apparatus, South Natick, MA) replaces the patient and the pump defines the pattern of breathing. The nebulizer mouthpiece is replaced by the inhaled mass filter, which captures all aerosol that would ordinarily be inhaled by a patient breathing with the specific breathing pattern set on the Harvard pump. To measure aerosol distribution, a cascade impactor can be interposed. Utilizing this scheme, many different devices can be tested on the bench without inconveniencing patients. In addition, variables that may affect nebulizer function, such as breathing pattern, are strictly controlled. European guidelines on the evaluation of nebulizer assessment have finally been drafted to take such factors into account and are mentioned briefly in the next chapter.
Aeroallergen sampling
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Estelle Levetin, Josh D. McLoud
Sieve impactors are used to collect airborne fungal spores or bacteria from outdoor or indoor environments for culturing. Airborne particles are drawn in through multiple holes and impact directly onto agar plates [11]. The original impactor of this type was a six-stage Andersen cascade impactor [41]. Each stage contains an open Petri dish with culture medium, and the cover plate for each stage has a sieve with 400 holes. The diameter of the holes decreases from 1.18 mm in stage 1 down to 0.25 mm in stage 6, and the particle cut size decreases as well from 7 μm down to 0.65 μm for stage 6. One- and two-stage models are also manufactured (https://www.thermofisher.com). The one-stage model (Figure 2.4), which consists of the sixth stage (N-6) from the original cascade impactor, is widely used in aerobiology research and has provided a wealth of data on culturable airborne fungi from both indoor and outdoor environments [42–45]. After the expiration of the patent, Andersen-type samplers have been produced by various other companies. A disposable version of the single-stage model, called the BioCassette device (https://www.emlab.com/), combines the sieve impactor and the Petri dish into a single unit. A study compared the BioCassette with a single-stage Andersen sampler and found no significant difference between total culturable fungi and Penicillium concentrations [46]. These sieve impactors all require an external pump capable of flow rates of 28.3 L/min. Sampling times generally range from 1 to 5 minutes. Many other types of sieve impactors are also available [11,25]. They differ in the number of openings in the sieve plate, the flow rate, and the optimum sampling time; some models even contain a sampling pump within the unit.
Bioequivalence of Orally Inhaled Drug Products: Challenges and Opportunities
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Jayne E. Hastedt, Elise Burmeister Getz
In vitro bioequivalence methods of aerosol sizing do not mimic the in vivo anatomy or airflow velocity profile; the results are not necessarily correctly interpreted as indicating in vivo deposition pattern. Rather, the bioequivalence objective is to use measures of (flow rate dependent) emitted dose and aerodynamic particle size as assays to characterize product differences (e.g. as a quality control test), on the basis that these metrics are primary determinants of regional deposition pattern. The cascade impactor is the most commonly used instrument for aerodynamic particle size measurement in bioequivalence testing. An induction port, typically designed to mimic the right angle turn of the throat, is attached to a series of stages, each comprising: (i) one or more nozzles through which the airstream flows and (ii) collection plates onto which particles with sufficient inertia as to be unable to follow bends in the airstream impact. The cascade impactor operates entirely via the inertial impaction mechanism, step-wise separating the aerosol into size “bins” according to the aerodynamic diameter which itself is a composite parameter that collectively represents the effects of such features as particle density and particle shape. Test and Reference products that are qualitatively and quantitatively similar in composition, have similar emitted dose, aerodynamic particle size distribution, pharmacokinetics, and local response, are deemed unlikely to have detectable differences in the rate and extent to which they present drug to the site(s) of action (both pharmacologic and toxicologic), i.e. are considered to be bioequivalent. Issues that potentially confound the use of inertial impaction as an assay of aerosol particle size distribution (APSD) sameness include product differences in particle composition (important when there are multiple solid-phase ingredients in a formulation) and dry powder inhaler (DPI) emptying rate (which affects the flow rate experienced by the formulation in vivo and the extent to which the inspiratory air in which the drug particle is entrained will penetrate the lungs).
Preparation and evaluation of vancomycin spray-dried powders for pulmonary delivery
Published in Pharmaceutical Development and Technology, 2021
Sara Bahrainian, Mohammadreza Rouini, Kambiz Gilani
The in vitro aerosolization behavior was determined using an Andersen cascade impactor. The recovered dose (RD) for all formulations varied between 92.48% and 99.64%. Emitted dose (ED%) and fine particle fraction (FPF%) data obtained for VCM after aerosolization of spray dried formulations by using an Aerolizer® are shown in Table 2. In vitro deposition data from different vancomycin DPI formulations aerosolized by an Aerolizer® are also presented as Supplementary data. The ED% for two- and three-component formulations ranged 50.02–92.36% and 65.54–94.07%, respectively. These data represent the considerable effect of HPBCD and LEU, used as second excipients in formulations, on ED%. Amaro et al. showed that addition of HPBCD to formulations composed of raffinose or trehalose could meaningfully increase ED% value compared to formulations comprised of only one excipient (Amaro et al. 2015). Aquino et al. also showed that the addition of LEU to dry powder inhalers of gentamicin substantially increases the ED% (Aquino et al. 2012).
Inhalable chitosan microparticles for simultaneous delivery of isoniazid and rifabutin in lung tuberculosis treatment
Published in Drug Development and Industrial Pharmacy, 2019
Ludmylla Cunha, Susana Rodrigues, Ana M. Rosa da Costa, Leonor Faleiro, Francesca Buttini, Ana Grenha
The aerodynamic assessment was determined as previously described in the literature [9], using the Andersen cascade impactor (ACI, Copley Scientific Ltd., Nottingham, UK) at a flow rate of 60 L/min. Cutoffs of the stages from −1 to 6 are the following: 8.60, 6.50, 4.40, 3.20, 1.90, 1.20, 0.55, and 0.26 µm. For each determination (n = 3), three capsules (HPMC size 3; Quali-V-I, Qualicaps, Madrid, Spain) were manually filled with microparticles (30 mg/capsule) and aerosolized using the RS01 dry powder inhaler (Plastiape Spa, Osnago, Italy). Aerosolized microparticles were rinsed with a mixture of water/acetonitrile (50/50, v/v), then sonicated (5 min), and filtered (0.45 µm, RC, Sartorius, Bohemia, NY). Drug deposition on each stage of the ACI was determined by HPLC (Agilent 1200 series, Darmstadt, Germany) at 275 nm (diode array detector). The mobile phase was phosphate buffer 20 mM pH = 7 (A) and acetonitrile (B). The gradient started with 95:5 (A:B) during 5 min, reaching a ratio of 30:70 (A:B), in the following 3 min, a condition kept for 19 min. The injection volume was 20 µL and the flow rate was set at 1 ml/min. Drug deposition on each stage was determined from standard calibration curves.
Spray-dried fucoidan microparticles for pulmonary delivery of antitubercular drugs
Published in Journal of Microencapsulation, 2018
Ludmylla Cunha, Ana M. Rosa da Costa, João P. Lourenço, Francesca Buttini, Ana Grenha
The in vitro aerosol performance of dry powders was assessed using the Andersen cascade impactor (ACI, Copley Scientific Ltd., UK). The methodology employed followed USP36 guidelines for dry powder inhalers (Apparatus 1, United States Pharmacopoeia, Chapter 601). A coating of 0.1% (v/v) Span® 85 in cyclohexane solution was used on the collection plates to prevent particle bounce. The cascade impactor was assembled in the specialised configurations for use at 60 L/min. Moreover, a glass fibre filter (Whatman, UK) was placed in the filter part (F) of the equipment to collect particles with a diameter lower than that of stage 6 cut-off (0.26 µm). The powder (30 mg) was loaded in hydroxypropyl methylcellulose size 3 capsules (Quali-V-I, Qualicaps, Spain) and the content of three capsules was discharged in each test. Powder formulations were aerosolised by Plastiape RS01 High Resistance (RS01-MR) inhaler and the drug retained in the capsule, inhaler, and impactor was collected using water/acetonitrile (50/50, v/v) and quantified by HPLC. The flow rate used during each test was adjusted with a Critical Flow Controller TPK (Copley Scientific, Nottingham, UK) in order to produce a pressure drop of 4 kPa across the inhaler. The flow rate corresponding to this pressure (65 L/min) was measured before each experiment using a DFM 2000 Flow Meter (Copley Scientific, Nottingham, UK). The test duration time was adjusted so that a volume of 4 L of air was drawn through each inhaler during each test.