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Pulmonary Delivery Fresh Air
echnology P Images: The T In the highly competitive world of drug discovery and development, By Iain McDerment at The Technology it is easy to focus on the early stages of identifying a candidate molecule or the fi rst critical rounds of clinical trials. However, in addition to selecting an attractive druggable target, the method of delivery is an equally important fi eld of research, since it can infl uence both product effi cacy and patient behaviour Drug delivery is big business, and can have a number of additional Currently, the major solutions estimates of the global market consequences to the patient. for non-invasive drug delivery for this area of technology put The route chosen can potentially are focused on the oral, inhaled, revenues at $122.3 billion in contribute to product line transdermal, ocular and nasal extensions, provide a more patient- routes, and make use of a expected rise to friendly dosage form, and play broad selection of devices and $198.4 billion in an important role in extending a technologies (2). Novel delivery 2017 (1). Clearly, medicine's lifecycle. Importantly, technology is essential for Inhaled drug delivery this is a market innovative drug delivery optimising drug efficacy, technology has the capacity reducing risk profiles and to improve the medication's potentially aiding patient User-friendly technology bioavailability, as well as its compliance. The development Over-the-counter market safety profi le (1). of new devices also opens up Innovations in Pharmaceutical Technology Issue 52


the interesting possibility of introducing products to specialised markets – paediatrics, for example. For this reason, some companies are now turning their attention to innovation in the area of drug delivery devices. Targeting the Lungs
Pulmonary delivery has been attracting interest recently due to the unique structure of the lung, which provides a large surface area, an exceedingly thin absorptive mucosal membrane and an excellent blood supply (3). These physiological parameters lend themselves very well as a mode of drug delivery, providing the benefits of a rapid onset of action, high local concentration and efficient Excessive degradation of a drug in the evolution of inhalation systemic delivery. The latter is of the liver (first-pass metabolism) is devices, including pressurised special interest for drugs that may also avoided when administered metered dose inhalers (pMDIs), otherwise have poor bioavailability via inhalation.
dry powder inhalers and liquid when administered orally (4).
aerosol devices. Many of the latest developments have been In the treatment of pulmonary completed with collaborative illnesses such as asthma and The pulmonary route is a efforts, benefiting from a large chronic obstructive pulmonary powerful means of enhancing pool of expertise. This article disease (COPD), inhaled delivery the administration of certain looks at some of the issues deposits the drug directly drugs, offering potentially that have been faced by those to affected areas at high improved bioavailability, lower developing inhalation devices.
concentrations. Additionally, doses and reduced side-effects this route means that the overall over traditional solid oral dosage amount of medicine needed to forms. However, developing A key problem commonly seen in be given to the patient is reduced: suitable devices can be challenging inhalation devices is that they lack one 4mg tablet of salbutamol, – the size of the inhaled particle, any features capable of informing for example, is the equivalent for example, is especially important: the user just how many doses 40 inhaled metered doses (3). too small and the particle will of a drug remain in an inhaler. This can minimise systemic be exhaled, yet overly large With a typical pMDI, the amount side-effects, as well as provide particles can adversely affect the of available drug must be guessed, a faster drug response.
throat and larynx (3). Another vital with patients typically having component of inhaled drug design to shake the device and simply From a pharmacological is ensuring that the device itself is estimate how much is left – but this perspective, inhaling a product user-friendly: capable of delivering can be hard to do accurately, given avoids many of the problems the medication efficiently, while the relative weights of the drug associated with swallowing, providing the patient with including poor solubility, low something pleasant to use. bioavailability, gut irritability, A collaboration between unwanted metabolites, food A wide variety of drug delivery AstraZeneca and The Technology effects and dosing variability (3). technologies are used to drive Partnership (TTP) aimed to address Innovations in Pharmaceutical Technology Issue 52


to meet requirements while frequencies against a body ensuring the safe administration of fluid, generating a stream of of an antiviral drug.
precisely controlled droplets. Initial in vivo work shows that Launched by Daiichi Sankyo, 83% of a delivered aerosol Japan's second largest appears on a lung scintigraph (6), pharmaceutical company, and in vitro measurements TwinCaps was marketed for the from human insulin (Velosulin®) delivery of its antiviral drug, and bovine serum albumin Invair®, and outsold Relenza and suggest TouchSpray is capable Tamiflu within the first six months. of aerosolising these with During in vitro tests, TwinCaps mean recovery rates in excess was shown to deliver 95% of the nominal dose at 20 litres per minute of airflow, and 100% at 25 litres per minute and above (5).
TouchSpray technology ultimately led to a collaborative Making the Perfect Droplet
effort between TTP and PARI, this issue, using a highly reliable The dry powder delivery culminating in the global launch counter in the form of a dial with devices mentioned thus far of the PARI eFlow® electronic Scintigraph showing deep lung penetration a colour display that sits atop the are innovative and useful in nebuliser – an inhaler that of aerosols using the device, with a clear dose count diverse ways, but these forms cuts patient treatment time by TouchSpray spray from 120 down to zero. The dial's are perhaps less than optimal 50%. The device enables liquid engine (diethylene triamine pentaacetic display provides users with a for the delivery of protein- and medication to be absorbed acid solution 3mg/mL, quantifiable number of doses peptide-based drugs. For this, through the lungs with as D[4,3] < 1μm) remaining in their inhaler, offering a liquid-based drug is superior, much as 90% efficacy.
both patient value and significant yet making liquid amenable to the pulmonary route has its This system uses a chamberless, own difficulties. Establishing an planar nozzle plate driven by optimal droplet size for inhalation a piezoelectric actuator, and In order to meet tight devices dispensing a liquid the inertial transfer mechanism commercial timelines driven drug is imperative: for efficient generates a highly defined by the Japanese government's deep lung penetration, a device aerosol of liquid droplets at the flu pandemic fears in 2006, a needs to produce respirable touch of a button. The technology project plan that went from droplets that increase – or at least is silent, discreet and portable, concept development to the maintain – drug efficacy, while making it easy to integrate first moulded prototypes in less eliminating the inclusion into patients' lives. than two months was needed. of additional propellants.
With the development of a two-component, single-dose, One possible solution is dry powder inhaler – Hovione's TouchSpray™ technology: a With so much information freely TwinCaps® by TTP – for systemic mechanism based on a nozzle available to an unprecedented delivery, it became possible plate that vibrates at ultrasonic amount of people via the internet, patients are more aware of the choices regarding their medication than ever before. While prescription treatments and devices continue to provide With so much information freely invaluable benefits to users available to an unprecedented around the world, there is a growing demand to provide amount of people via the internet, patients with the range of options patients are more aware of the they expect from consumer products in their healthcare. choices regarding their medication In an era of choice, the trend is likely to be a move towards the Innovations in Pharmaceutical Technology Issue 52



development of specifi c over-the- Understandably, some companies 2. Chow Chan C, Chow K, counter (OTC) devices.
are looking towards the OTC market McKay B and Fung M, as a strategic expansion of their Therapeutic Delivery As patients start selecting OTC existing medical device portfolio. Solutions, John Wiley & devices, an appealing design, With inhalation-based delivery Sons, p424, 2014. ISBN: coupled with recognition of devices providing so many benefi ts their needs, is going to be over their solid oral counterparts, 3. Chaturvedi NP and Solanki K, exceptionally important as it seems logical to apply these Pulmonary drug delivery these users become more akin innovative technologies to OTC system: Review, Int J App to consumers – choosing their medications. Such a venture could Pharm 5(3): pp7-10, 2013 preferred device and formulation provide patients with a valuable and 4. Olsson B et al, Pulmonary when visiting pharmacies and convenient alternative to traditional drug metabolism, clearance, dosage forms, a more effi cacious and absorption, in Controlled version of commonly used drugs, Pulmonary Drug Delivery, The OTC Market
and the opportunity for companies Advances in Delivery Science to capture market share along and Technology, Smyth HDC People frequently turn to OTCs at and Hickey AJ (eds), Chapter 2, the fi rst sign of disease symptoms, rather than visiting a doctor and Delivering an Alternative
5. TwinCaps® A simple, requesting prescription drugs. disposable and cost-effective In this context, OTC medicines Delivery of drugs via the inhalation dry powder inhaler with effectively provide people route rather than the traditional excellent performance, with round-the-clock access oral (swallowing) route has not Hovione press release. Visit: to treatment. This reliance upon only provided effective ways of such products is one of the treating pulmonary diseases, but reasons the market has become sparked an array of innovative so profi table: in the US alone, technological breakthroughs. it was valued at $17.4 billion in By providing solutions to patient 2011 (8) – an impressive fi gure problems, companies are ensuring 6. Blackely D et al, Drug Delivery that could exceed $106 billion that user needs are at the heart of to the Lungs conference worldwide by 2017 (9).
their concept and development proceedings (DDL IX), programmes, while making It is not just patients that benefi t signifi cant contributions to et al, Drug Delivery from the existence of OTCs: their healthcare and wellbeing in to the Lungs conference widespread use helps to reduce proceedings (DDL XII), the burden on straining healthcare systems through fewer visits to Drug delivery technology is 8. About Money, The over-the- local doctors, for example. One already a sizable market, and is counter drug industry. Visit: estimate of the fi nancial boon about to expand further with that OTCs bring is a saving to companies now looking to apply US healthcare of $102 billion their technologies to the OTC annually (10).
sector, aiming to cater to patient needs while developing robust, 9. Companies and Markets, effective devices. With all of this World OTC pharmaceutical Iain McDerment, Consultant Engineer in mind, innovative drug delivery market 2013-2023. Visit: at The Technology Partnership, has 19 technologies are going to be vital years of experience in consulting and to stand out from the competition. drug delivery device development, and holds a BEng in Mechanical Engineering. His specialities encompass early-stage conceptual development through to late-stage design 1. VisionGain press release. for manufacture. Iain has led many drug delivery device developments from concept to high-volume production, 10. Consumer Healthcare including the Daiichi-Sankyo Inavir inhaler. He is listed as Products Association, an inventor on over 25 patents, predominantly in drug Statistics on OTC use, 2014. delivery. Email: enquiries@ttp.com Visit: www.chpa.org/ Innovations in Pharmaceutical Technology Issue 52

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Trimble dini digital level user guide

Trimble® DiNi® Digital Level Version 2.0Part Number 57345002December 2007 Corporate OfficeTrimble Navigation Limited 645 North Mary Avenue PO Box 3642 Sunnyvale, CA 94085 Geomatics and Engineering Division 5475 Kellenburger Road Dayton, Ohio 45424-1099 USA800-538-7800 (toll free in USA)