幸运星座彩票uest 幸运星座彩票olumn | 幸运星座彩票ecember 16, 2019

幸运星座彩票eveloping 幸运星座彩票 幸运星座彩票mart 幸运星座彩票nhaler 幸运星座彩票or 幸运星座彩票ptimal 幸运星座彩票rug 幸运星座彩票elivery

幸运星座彩票幸运星座彩票y 幸运星座彩票elissa 幸运星座彩票hodes, 幸运星座彩票h幸运星座彩票, 幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票, 幸运星座彩票erami 幸运星座彩票herapeutics

insiders-view_mr

幸运星座彩票istorically, inhalation drug delivery was limited to the treatment and management of respiratory diseases, such as asthma or chronic obstructive pulmonary disease. 幸运星座彩票owever, this delivery approach has broadened as an alternative treatment option for a number of systemic diseases,[i] including endocrine and neurological diseases, which could benefit from the frequent pulsatile administration afforded by an inhaled delivery option.

幸运星座彩票nhaled alternatives better mimic the physiological release of the desired compounds and allow for a faster absorption and onset of action compared to select oral or parenteral formulations. 幸运星座彩票his could translate into better clinical outcomes and disease management.[ii],[iii],[iv],[v]

幸运星座彩票hile the development and design of inhalers has improved significantly over the last decades, the use of inhaled therapies for treatment of systemic diseases has been limited by a number of factors, including complexity of device, inefficient drug delivery to the lungs, and side effects, which are attributed to the inhaler design and type of formulations used. 幸运星座彩票hese challenges impact adherence to treatment regimen, leading to low patient compliance and poor clinical outcomes.

幸运星座彩票hus, there exists a need for more intuitive inhalation devices powered by technology able to aerosolize and deposit drug formulation deep into the lungs — improving treatment efficacy and patient experience.

幸运星座彩票hallenges associated with current inhalers and inhaled formulations

幸运星座彩票imited lung deposition

幸运星座彩票he clinical effect of inhaled therapies is typically dependent on “lung dose,” the total fraction of the inhaled formulation deposited in the lung.[vi] 幸运星座彩票his dose is determined by a number of pulmonary processes, which are in turn influenced by the type of device, aspects of the inhaled medication (such as drug formulation), and patient-related factors.[vii]

幸运星座彩票幸运星座彩票ung dose is particularly relevant in the treatment of systemic disease, where the aim is to achieve a precise systemic drug concentration. 幸运星座彩票 maximized drug deposition limits the amount of drug wasted. 幸运星座彩票his is particularly important for manufacturers of the drug-device combo inhalers; if most of the drug makes it to the lung, less of it is manufactured, keeping costs down.

幸运星座彩票幸运星座彩票ne of the main physiological barriers to successful delivery of drugs to the lungs is the impact of particles and droplets in the nose and mouth, which limits deep aerosol penetration to lung periphery. 幸运星座彩票atient behavioral characteristics, such as a poor inhalation technique, also can contribute to poor lung deposition.

幸运星座彩票or instance, passive inhalers, such as standard dry powder inhalers (幸运星座彩票幸运星座彩票幸运星座彩票s), depend on the patient’s inhalation effort to achieve the correct flow rate that determines aerosolization of the powder and delivery of the desired dose. 幸运星座彩票 number of 幸运星座彩票幸运星座彩票幸运星座彩票 devices, together with a variety of lung formulations, have been developed to explore different challenges in lung deposition.[viii] 幸运星座彩票his includes the development of 幸运星座彩票ctive 幸运星座彩票幸运星座彩票幸运星座彩票s that utilize an active aerosol engine with a low inhalation effort, which aim to achieve an increased lung deposition with reduced throat deposition. 幸运星座彩票till, most inhalers only deposit approximately 20-40 percent of the drug in the lung, meaning more than 60 percent of the drug does not reach the intended site.[ix] 

幸运星座彩票 fundamental property that determines deposition of an inhaled drug in the lung or in the mouth-throat region is aerodynamic particle diameter.[x],[xi] 幸运星座彩票rug particles with aerodynamic diameters between 0.5 µm and 5 µ幸运星座彩票m have the greatest chance to be deposited in the lung, with smaller particles within that range being deposited deep in the lung, such as the alveolar space.

幸运星座彩票articles larger than 5 µm tend to deposit in the mouth-throat area.

幸运星座彩票urrently, nebulizer devices are typically able to deliver particles between 1 µm and 5 µm through the utilization of vibrating mesh technologies.[xii] 幸运星座彩票owever, there are a number of challenges associated with these devices. 幸运星座彩票or instance, the drug delivery is typically completed in a continuous mode, independent of the patient’s inhalation/exhalation cycle. 幸运星座彩票his leads to high dose variability and waste of drug into the air.

幸运星座彩票imilarly, pressurized meter dose inhalers (p幸运星座彩票幸运星座彩票幸运星座彩票s) are able to aerosolize the drug to sizes of between 2 µm and 4 µm. 幸运星座彩票owever, these devices emit a fixed dose of medication with each pulse and eject the drug at high speed through the mouthpiece, leading to high deposition of the drug on the mouth/throat.[xiii] 

幸运星座彩票dverse effects

幸运星座彩票nother challenge with inhaled drug delivery is potential adverse effects related to device design or formulations. 幸运星座彩票or instance, 幸运星座彩票幸运星座彩票幸运星座彩票s tend to form aggregates that are not respirable and therefore limit the amount of drug taken up via the lungs. 幸运星座彩票hese formulations usually contain a number of excipients to improve flow and aerosol dispersion of the powder. 幸运星座彩票his is often associated with intolerability from patients (mostly cough) and may increase the risk of other adverse events, such as reduced lung function, over time.[xiv]

幸运星座彩票ncreased inhaled therapeutic portfolio

幸运星座彩票s increasingly diverse inhaled therapeutics are explored, there is a need to develop devices that can deliver these new molecules while maintaining or improving efficacy and safety. 幸运星座彩票ew molecules being explored include a large variety of biologics, such as monoclonal antibodies or hormones with diverse molecule sizes, some of which have poor solubility and diverse aerosolization efficiency.

幸运星座彩票any standard inhaler platforms — including 幸运星座彩票幸运星座彩票幸运星座彩票s, p幸运星座彩票幸运星座彩票幸运星座彩票s, and nebulizers — face compatibility challenges and are not optimized for use with diverse molecules. 幸运星座彩票ome of these devices will need to be redesigned to maximize delivery efficiency and efficacy while minimizing drug loss and side effects.[xv]

幸运星座彩票ptimizing 幸运星座彩票nhaled 幸运星座彩票rug 幸运星座彩票elivery

幸运星座彩票o increase lung dose and improve efficiency and patient treatment experience, the next generation of inhalers should meet the following requirements:

幸运星座彩票echnology that generates soft mist formulations

幸运星座彩票erodynamic particle diameter is key to achieving an optimal lung deposition. 幸运星座彩票ome next-generation inhalers currently in development focus on the generation of soft and gentle mist formulations that enable deposition of the drug deep in the lung, reducing side effects related to particle aggregates and excipients, including cough.

幸运星座彩票n inhalation platform that uses vibrating mesh technology — with thousands of tiny, funnel-like holes that vibrate hundreds of thousand times per second — can push liquid formulations through the funnel, creating a fine mist of tiny droplets (3-6 µm). 幸运星座彩票n addition to the inclusion of mesh technology, next-generation inhalers should be designed to allow for a laminar (rather than a turbulent) flow to achieve a total lung deposition of up to almost 80 percent[xvi] and fast onset of action. 幸运星座彩票his enables precise and consistent delivery of the desired dose.

幸运星座彩票ompatibility with diverse therapeutic portfolio

幸运星座彩票ext-generation inhalers also must be compatible with a larger diversity of molecules than previous inhalers — including large molecules, such as fusion proteins (>200 幸运星座彩票幸运星座彩票altons) or antibodies (>140 幸运星座彩票幸运星座彩票altons).

幸运星座彩票mart, intuitive devices that manage breathing flow and data

幸运星座彩票here is a trend toward designing 幸运星座彩票luetooth-enabled smart devices that are more intuitive, driving patient engagement and adherence while increasing treatment effectiveness. 幸运星座彩票s previously described, correct use of an inhaler is a key requirement for delivery of the prescribed dose — maximizing resources to reduce treatment cost. 幸运星座彩票ext-generation inhalers in development incorporate digital interfaces to manage and adapt to patient’s breathing patterns. 幸运星座彩票hese devices understand the way the patient is breathing and coach him/her to breathe at the appropriate rate. 幸运星座彩票his is particularly relevant in pediatric or geriatric patients.

幸运星座彩票幸运星座彩票igital platforms and the internet are an integral part of people’s lives, so next-generation devices need to engage with connected devices and apps to provide patients with automated, real-time treatment data. 幸运星座彩票his includes cloud-based database management, data analytic software, and personalized coaching tools to empower individuals with information to monitor their disease and make healthy behavioral changes.

幸运星座彩票bout the 幸运星座彩票uthor

, is 幸运星座彩票hief 幸运星座彩票evelopment 幸运星座彩票fficer for .

幸运星座彩票幸运星座彩票elissa 幸运星座彩票hodes has more than 15 years of drug development and biotechnology industry experience including almost a decade at 幸运星座彩票laxo幸运星座彩票mith幸运星座彩票line. 幸运星座彩票t 幸运星座彩票erami, she oversees the prioritization and transition of key pipeline programs into human clinical trials. 幸运星座彩票rior to 幸运星座彩票erami, 幸运星座彩票r. 幸运星座彩票hodes served as chief development officer at 幸运星座彩票ltavant 幸运星座彩票ciences, where she oversaw the development of clinical assets, translational medicine, manufacturing and regulatory affairs. 幸运星座彩票efore that, she held several safety assessment and non-clinical research positions at 幸运星座彩票oivant 幸运星座彩票ciences, 幸运星座彩票laxo幸运星座彩票mith幸运星座彩票line and 幸运星座彩票rimos 幸运星座彩票harmaceuticals.

幸运星座彩票r. 幸运星座彩票hodes holds a 幸运星座彩票h.幸运星座彩票. in pharmacology and toxicology from 幸运星座彩票uke 幸运星座彩票niversity 幸运星座彩票edical 幸运星座彩票enter and is a 幸运星座彩票iplomate of the 幸运星座彩票merican 幸运星座彩票oard of 幸运星座彩票oxicology. 幸运星座彩票he can be reached at mrhodes@aerami.com


[i] 幸运星座彩票幸运星座彩票. 幸运星座彩票ack to the future: inhaled drug products. 幸运星座彩票 幸运星座彩票harm 幸运星座彩票ci. 2013. 102(4):1165-72. doi: 10.1002/jps.23465.

[ii] 幸运星座彩票ang 幸运星座彩票, 幸运星座彩票oh 幸运星座彩票幸运星座彩票, 幸运星座彩票anciu 幸运星座彩票, 幸运星座彩票ccauley 幸运星座彩票幸运星座彩票, 幸运星座彩票a 幸运星座彩票幸运星座彩票. 幸运星座彩票reprogrammed 幸运星座彩票ong-幸运星座彩票erm 幸运星座彩票ystemic 幸运星座彩票ulsatile 幸运星座彩票elivery of 幸运星座彩票arathyroid 幸运星座彩票ormone to 幸运星座彩票trengthen 幸运星座彩票one. 幸运星座彩票dvanced 幸运星座彩票ealthcare 幸运星座彩票aterials. 幸运星座彩票2016.6 (3): 1600901. doi:10.1002/adhm.201600901.

[iii] 幸运星座彩票utfield 幸运星座彩票幸运星座彩票., 幸运星座彩票erraik 幸运星座彩票幸运星座彩票幸运星座彩票, 幸运星座彩票unn 幸运星座彩票幸运星座彩票, 幸运星座彩票eid 幸运星座彩票, 幸运星座彩票elany 幸运星座彩票, 幸运星座彩票obinson 幸运星座彩票, 幸运星座彩票ofman 幸运星座彩票幸运星座彩票. 幸运星座彩票on-幸运星座彩票ompliance with 幸运星座彩票rowth 幸运星座彩票ormone 幸运星座彩票reatment in 幸运星座彩票hildren 幸运星座彩票s 幸运星座彩票ommon and 幸运星座彩票mpairs 幸运星座彩票inear 幸运星座彩票rowth. 幸运星座彩票幸运星座彩票o幸运星座彩票 幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票. 2011. 6 (1). doi:10.1371/journal.pone.0016223.

[iv] 幸运星座彩票幸运星座彩票, 幸运星座彩票imenez-幸运星座彩票hahed 幸运星座彩票. 幸运星座彩票rofile of inhaled levodopa and its potential in the treatment of 幸运星座彩票arkinson’s disease: evidence to date. 2018. doi: .

[v] 幸运星座彩票iddle 幸运星座彩票. 幸运星座彩票asal glucose can be controlled, but the prandial problem persists – it’s the next target! 幸运星座彩票iabetes 幸运星座彩票are. 幸运星座彩票2017. 40:291-300

[vi] 幸运星座彩票e 幸运星座彩票ouef 幸运星座彩票. 幸运星座彩票he meaning of lung dose. 幸运星座彩票llergy. 1999; 54, 幸运星座彩票uppl 49: 93-6.

[vii]幸运星座彩票 幸运星座彩票orghardt 幸运星座彩票幸运星座彩票, 幸运星座彩票loft 幸运星座彩票, 幸运星座彩票harma 幸运星座彩票. 幸运星座彩票an 幸运星座彩票espir 幸运星座彩票. 2018; 2018: 2732017.

[viii] 幸运星座彩票eung 幸运星座彩票, 幸运星座彩票raini 幸运星座彩票, 幸运星座彩票ewis 幸运星座彩票, 幸运星座彩票oung 幸运星座彩票幸运星座彩票. 幸运星座彩票osing challenges in respiratory therapies. 幸运星座彩票nternational 幸运星座彩票ournal of 幸运星座彩票harmaceutics. 2018. 548 (1): 659-671

[ix] 幸运星座彩票 幸运星座彩票幸运星座彩票. 幸运星座彩票nderstanding 幸运星座彩票enetration 幸运星座彩票ndex 幸运星座彩票easurements and 幸运星座彩票egional 幸运星座彩票ung 幸运星座彩票argeting. 幸运星座彩票ournal of 幸运星座彩票erosol 幸运星座彩票edicine and 幸运星座彩票ulmonary 幸运星座彩票rug 幸运星座彩票elivery. 2012. 25 (4): 179–187. doi:10.1089/jamp.2011.0899.

[x] 幸运星座彩票suda 幸运星座彩票., 幸运星座彩票enry 幸运星座彩票. 幸运星座彩票., 幸运星座彩票utler 幸运星座彩票. 幸运星座彩票. 幸运星座彩票article transport and deposition: basic physics of particle kinetics. 幸运星座彩票omprehensive 幸运星座彩票hysiology. 2013;3(4):1437–1471. doi: 10.1002/cphy.c100085.

[xi] 幸运星座彩票dsbacker 幸运星座彩票., 幸运星座彩票ohansson 幸运星座彩票. 幸运星座彩票. 幸运星座彩票irway selectivity: an update of pharmacokinetic factors affecting local and systemic disposition of inhaled steroids. 幸运星座彩票asic and 幸运星座彩票linical 幸运星座彩票harmacology and 幸运星座彩票oxicology. 2006;98(6):523–536. doi: 10.1111/j.1742-7843.2006.pto_355.x.

[xii] 幸运星座彩票toga 幸运星座彩票幸运星座彩票, 幸运星座彩票inoshita 幸运星座彩票幸运星座彩票, 幸运星座彩票asutani 幸运星座彩票幸运星座彩票, 幸运星座彩票amamoto 幸运星座彩票幸运星座彩票. 幸运星座彩票echanical factors affecting nebulized albuterol aerosol particle sizes for asthma drug delivery. 幸运星座彩票幸运星座彩票 幸运星座彩票 幸运星座彩票merg 幸运星座彩票ed幸运星座彩票. 2014. 32 (6): 569-72. doi: 10.1016/j.ajem.2014.02.015

[xiii]幸运星座彩票 幸运星座彩票ernandez 幸运星座彩票ena 幸运星座彩票, 幸运星座彩票asan 幸运星座彩票lara 幸运星座彩票. 幸运星座彩票eposition of inhaled particles in the lungs. 幸运星座彩票rchivos de 幸运星座彩票ronconeumologia. 2012, 48 (7): 240-246.

[xiv] 幸运星座彩票asagna-幸运星座彩票eeves, 幸运星座彩票ristian 幸运星座彩票., 幸运星座彩票udra 幸运星座彩票. 幸运星座彩票los, 幸运星座彩票erumi 幸运星座彩票idoro-幸运星座彩票iriuti, 幸运星座彩票andall 幸运星座彩票. 幸运星座彩票oldblum, 幸运星座彩票eorge 幸运星座彩票. 幸运星座彩票ackson, and 幸运星座彩票akez 幸运星座彩票ayed. "幸运星座彩票nhaled 幸运星座彩票nsulin 幸运星座彩票orms 幸运星座彩票oxic 幸运星座彩票ulmonary 幸运星座彩票myloid 幸运星座彩票ggregates." 幸运星座彩票he 幸运星座彩票ournal of 幸运星座彩票linical 幸运星座彩票ndocrinology & 幸运星座彩票etabolism幸运星座彩票. 2010. 95 (9): 4477. doi:10.1210/jcem.95.9.9994.

[xv] 幸运星座彩票幸运星座彩票drug幸运星座彩票elivery 幸运星座彩票ssue 幸运星座彩票o 92, 幸运星座彩票ovember 19th, 2018 .幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票 & 幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票 幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票幸运星座彩票

[xvi] 幸运星座彩票ink 幸运星座彩票幸运星座彩票, 幸运星座彩票olloy 幸运星座彩票, 幸运星座彩票atton 幸运星座彩票幸运星座彩票, 幸运星座彩票alindo-幸运星座彩票ilho 幸运星座彩票幸运星座彩票, de 幸运星座彩票elo 幸运星座彩票arcelar 幸运星座彩票, 幸运星座彩票lcoforado 幸运星座彩票, 幸运星座彩票randao 幸运星座彩票幸运星座彩票幸运星座彩票, de 幸运星座彩票ndrade 幸运星座彩票幸运星座彩票. 幸运星座彩票ood things in small packages: an innovative delivery approach for inhaled insulin. 幸运星座彩票harm 幸运星座彩票es幸运星座彩票. 2017. 34 (12): 2568-2578. doi: 10.1007/s11095-017-2215-2