Aerodynamic Particle Size Testing
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
Nebulizing systems differ from the other orally inhaled products because they provide the API(s) in a continuous stream of aqueous droplets for the duration of the treatment period, instead of delivering a bolus of medication following actuation or when the user inhales (Hess 2000). Typical treatment times for nebulizer-based therapies are often many minutes in duration. Nebulizer-generated aqueous droplets generally do not require coated collection surfaces when sampled by cascade impactor, as they adhere strongly to the collection surface once impacted there. The determination of the sampling time for an APSD determination is therefore limited by the droplet delivery rate of the nebulizer, the fill of liquid containing medication in its reservoir and, most importantly, the need to avoid overloading the collection surfaces of the impactor stages with collected droplets. It is self-evident that cascade impactors that make use of collection plates are more vulnerable to stage overload rather than those apparatuses that use cups to collect the impacted droplets. A pilot study to establish a suitable sampling time per determination is therefore a prudent precaution in method development involving nebulizer testing, especially when an impactor with collection plates is chosen.
Nanosuspensions as Nanomedicine: Current Status and Future Prospects
Debarshi Kar Mahapatra, Sanjay Kumar Bharti in Medicinal Chemistry with Pharmaceutical Product Development, 2019
Nanosuspensions may prove to be an ideal approach for delivering drugs that exhibit poor pulmonary absorption. Current formulations like suspension aerosols, inhalers shows a limited diffusion and dissolution of the drug at the site of action because of its poor solubility and microparticulate nature, which may affect the bioavailability of the drug, rapid clearance of the drug from the lungs because of ciliary movements [148], less residence time for the drugs, leading to absence of prolonged effect, unwanted deposition of the drug particles in pharynx and mouth. Nanosuspensions can solve the problems associated with conventional systems because of their versatile nature. The nanoparticulate nature of the drug allows the rapid diffusion and dissolution of the drug at the site of action. At the same time, the increased adhesiveness of the drug to mucosal surfaces [149] offers a prolonged residence time for the drug at the absorption site. They prevent unwanted deposition of particles in the mouth and pharynx, leading to decreased local and systemic side effects of the drug. Nanosuspensions could be used in all available types of nebulizer. However, the extent of influence exerted by the nebulizer type as well as the nebulization process on the particle size of nanosuspensions should be ascertained.
Amphotericin B Deoxycholate
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Aerosolized AMB has been used as a mode of delivery for the prevention of invasive fungal infection (IFI)—in particular aspergillosis in neutropenic and lung transplant patients—as it offers the prospect of drug delivery to the most common site of infection while minimizing the toxicity associated with intravenous administration. Effective aerosol delivery depends on an efficient nebulizer and the mean mass aerodynamic diameter (MMAD), with an optimal particle size of 1–5 µm for deposition in the small airways (Le and Schiller, 2010). Patient technique is also critical to the effective use of any nebulizer. Preclinical studies using rat models support the feasibility of aerosolized AMB. One study found a concentration of 2.79 µg/g in lung tissue after a single aerosol dose of 1.6 mg/kg of AMB and 9.88 µg/g after four doses, with no systemic exposure to the drug. The elimination half-life of AMB from the lungs was 4.8 days (Niki et al., 1990). In one study, the MMAD was 1.36 µm, and lung concentration after 60 minutes nebulization was 24.2+/–6.4 µg/g with radiolabeling demonstrating no distribution to sites other than the lungs and the gastrointestinal tract (Ruijgrok et al., 2000). A single dose of aerosolized AMB given 2 days before infection delayed mortality in a rat model of invasive aspergillosis (Schmitt et al., 1988). In the clinical setting, a study of lung transplant recipients showed mean concentrations of AMB in bronchioalveolar secretions of 1.46 µg/ml at 4 hours and 0.37 µg/ml after 24 hours, while in bronchioalveolar lavage fluid (BAL) concentrations of 15.75 µg/ml and 11.02 µg/ml were observed at 4 and 24 hours respectively.
Effects of haloperidol inhalation on MK-801- and memantine-induced locomotion in mice
Published in Libyan Journal of Medicine, 2020
Hiroshi Ueno, Shunsuke Suemitsu, Shinji Murakami, Naoya Kitamura, Kenta Wani, Yu Takahashi, Yosuke Matsumoto, Motoi Okamoto, Takeshi Ishihara
The neurofilaments of the olfactory nerve or axons extending directly from the olfactory bulb in the marginal area of the brain to the upper back of the nose penetrate the mucosal lining and make direct contact with the outside world. This unique and important anatomical arrangement may provide a potential pathway for direct drug access to the CNS [7,10,9]. In fact, some drugs are already administered intranasally, such as sumatriptan for migraine headaches and desmopressin for the treatment of diabetes mellitus in response to lactation [10,13]. Current nasal administration protocols require that a liquid containing the drug is inhaled using a dedicated device [12,15]. In this study, we investigated whether delivering a drug to the brain is possible by inhalation without using a dedicated device (e.g., inhalation using aromatherapy). In this study, mice inhaled the CNS depressants haloperidol and betahistine using a nebulizer. The mechanism of action of the nebulizer is the same mechanism which is used in aromatherapy to convert essential oils into fine air particles for inhalation.
Estimating the impact of self-management education, influenza vaccines, nebulizers, and spacers on health utilization and expenditures for Medicaid-enrolled children with asthma
Published in Journal of Asthma, 2021
Melike Yildirim, Paul Griffin, Pinar Keskinocak, Jean C. O’Connor, Julie L. Swann
A nebulizer is a device to deliver liquid medication to the lungs accurately, and spacers are recommended to use with inhalers to provide a required amount of medication, especially by children who have difficulty inhaling correctly. Proper usage of medications and required dose leads to a better response (8). Two types of medications (controllers and relievers) are commonly used for asthma treatments. Relievers work on acute symptoms and provide quick relief, whereas controller medications are used regularly to prevent asthma attacks. Improving adherence to asthma medications and devices can reduce the utilization cost of visits due to fewer ED visits and hospitalizations (9). For patients whose asthma remains uncontrolled despite medical management, AS-ME helps patients manage asthma triggers and symptoms and reduce asthma exacerbation (10). Patients with asthma have an increased risk of severe symptoms with influenza. Flu vaccines can decrease the risk of asthma attacks, which is triggered by flu infection (11). Although clinical guidelines have recommended AS-ME and prescription of a spacer with an inhaler (7), they are not widely implemented, and their net benefits are uncertain.
Continuous infusion aerosol delivery of prostacyclins during mechanical ventilation: challenges, limitations, and recent advances
Published in Expert Opinion on Drug Delivery, 2022
Michael McPeck, Gerald C. Smaldone
Contemporary continuous infusion aerosol delivery during mechanical ventilation is a technologically complex procedure employing specialized equipment [5]. The nebulizer is replenished continuously by a calibrated infusion pump and delivers its aerosol output into the heated and humidified ventilator circuit in a manner that enables a portion of the nebulizer output to be inhaled by the patient. The portion of aerosol drug inhaled is termed Inhaled Mass, IM, and is expressed as the percentage of drug mass delivered to the nebulizer with respect to time. Traditionally, drug dose delivered in this manner may also be expressed as the actual drug mass (in mg or µg) delivered during a specific time. However, also expressing it as a percentage of the volume infused into the nebulizer provides a measure of the efficiency of the complete drug delivery system.
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