A NOVEL DEVICE PLATFORM ARTIFICIAL NEURAL SCOPING THE DESIGN FOR LIQUID AEROSOL DRUG- NETWORKS FOR INHALED SPACE FOR GENERIC P13 DEVICE COMBINATIONS P18 FORMULATION DEVELOPMENT P32 NASAL SPRAYS PULMONARY & NASAL DRUG DELIVERY 50 O ISSUE N • , 2014 , 2014 TH JUNE 19 Contents ONdrugDelivery Issue No 50, June 19th, 2014 Pulmonary & Nasal Drug Delivery CONTENTS This edition is one in the ONdrugDelivery series of publications from Frederick Furness Publishing. Each issue focuses on a specific topic within the field of Scale-up & QbD Approaches for Spray-Dried drug delivery, and is supported by industry leaders Inhalation Formulations in that field. Dr Eunice Costa, Scientist, Drug Product EDITORIAL CALENDAR 2014/15 Development; Dr Filipe Neves, Senior Scientist, Group Leader, Drug Product Development; July: Novel Oral Delivery Systems 03 - 08 Sep: Prefilled Syringes Dr Gonçalo Andrade, Business Development Oct: Drug Formulation & Delivery Solutions Manager; and Dr Conrad Winters, & Services Director, Drug Product Development Nov: Pulmonary & Nasal Drug Delivery Hovione Dec: Delivering Biotherapeutics Jan: Ophthalmic Drug Delivery Product Profile: Feb: Prefilled Syringes 10 - 12 Teamed: For Drug Delivery Device Products March: Transdermal Delivery, Microneedles & Needle-Free Injection The eFlow “Closed System” (CS) – A Novel April: Pulmonary & Nasal Drug Delivery Device Platform for Liquid Aerosol Drug-Device May: Injectable Drug Delivery: Devices Focus Combinations 13 - 16 Mr Thomas Gallem, Director, eFlow Product SUBSCRIPTIONS: Design & Lifecycle Management To arrange your FREE subscription (pdf or print) PARI Pharma GmbH to ONdrugDelivery Magazine: Artificial Neural Networks & Tissue E: [email protected] Models for Inhaled Formulation Screening, SPONSORSHIP/ADVERTISING: Selection & BE Testing Jo Muddle, MedPharm & KCL PhD Student; Contact: Guy Furness, Proprietor & Publisher Professor Clive Page, Professor of Pharmacology, T: +44 (0) 1273 78 24 24 18 - 20 E: [email protected] Head of Sackler Institute of Pulmonary Pharmacology; and Professor Marc Brown, Chief MAILING ADDRESS: Scientific Officer & Chief Operating Officer Frederick Furness Publishing Ltd MedPharm Ltd The Candlemakers, West Street, Lewes, Conference Review: East Sussex, BN7 2NZ, United Kingdom 24 Respiratory Drug Delivery (RDD) 2014 ONdrugDelivery Magazine is published by Frederick Furness Publishing Ltd. Registered Office: Formulation Methods & Size Reduction for Inhalers The Candlemakers, West Street, Lewes, Mr Bert Dekens, Team Manager, Pharma East Sussex, BN7 2NZ, United Kingdom. 26 - 28 Hosokawa Micron BV Registered in England: No 8348388. VAT Registration No: GB 153 0432 49. Generic pMDI Product Development for the US: ISSN 2049-145X print Key Considerations ISSN 2049-1468 pdf 29 - 31 Mr Badre Hammond, Associate Director, Copyright © 2014 Frederick Furness Publishing Ltd Business Development All rights reserved Next Breath, LLC Scoping the Design Spac for Generic Nasal Sprays Dr Deborah Huck-Jones, Product Manager, Analytical Imaging; and Dr Paul Kippax, 32 - 35 Micrometrics Product Group Manager & Pharmaceutical Portfolio Manager Malvern Instruments Ltd The views and opinions expressed in this issue are those of the authors. Due care has been used in producing this publication, but the publisher makes no claim that it is free of error. Nor does the publisher accept liability for the consequences of any decision or action taken (or not taken) as a result of any information contained in this publication. Wednesday 10th to Friday 12th December 2014 Front cover image, “Design Concept Drawing by Cambridge Consultants for PARI’s eFlow® CS nebuliser”, provided by PARI Edinburgh International Conference Centre Pharma GmbH (see this issue, page 13). Reproduced with Submissions for podium and poster presentations are invited kind permission. 2 www.ondrugdelivery.com Copyright © 2014 Frederick Furness Publishing Ltd Hovione SCALE-UP & QBD APPROACHES FOR SPRAY-DRIED INHALATION FORMULATIONS Here, Eunice Costa, PhD, Scientist, Drug Product Development; Filipe Neves, PhD, Senior Scientist, Group Leader, Drug Product Development; Gonçalo Andrade, PhD, Business Development Manager; and Conrad Winters, PhD, Director, Drug Product Dr Eunice Costa Development, all of Hovione, describe the strong position of inhalable products in Scientist, Drug Product Development preclinical and clinical pipelines and make the case for formulation-based approaches to enable and enhance pulmonary product development. Spray-drying technology in particular is highlighted as a highly favourable, scalable manufacturing technique for inhalable composite particles. INHALED DRUG DELIVERY alternative, reducing the need for medically trained staff during administration. Also, Inhaled drug delivery is a growing niche compared with parenteral formulations, market within the pharmaceutical indus- DPIs may not require the refrigeration often Dr Filipe Neves Senior Scientist, Group Leader, try. Pulmonary drug delivery accounted for necessary for vaccines and, when compared Drug Product Development US$19.6 billion (£11.6 billion) in revenues in with the oral route, lower doses can be used 20101 and represented approximately 15% with the potential for reduced side effects. of the drug delivery market.2 Inhalation For drug molecules that have a pro- is emerging as an alternate drug delivery nounced food effect, extensive first-pass route, expected to reach $44 billion by 2016 metabolism, or are subject to efflux or 1 and representing approximately 20% of low aqueous solubility, pulmonary delivery the drug delivery market by 2017.2 This offers a viable route where oral delivery growth will be driven by new drug product would be extremely challenging. launches for unmet clinical needs, novel This high number of projects pres- Dr Gonçalo Andrade drug product combinations and products for ently in clinical development (Figure 1) Business Development Manager improving patient compliance, where pres- reflects different development strategies, surised metered-dose inhalers (pMDIs) and ranging from lifecycle management strate- dry-powder inhalers (DPIs) are expected to gies related to inhaler redesign, such as be the major contributors (15.7% CAGR AstraZeneca’s ongoing Symbicort (bude- and 12.3% CAGR, respectively).1 sonide + formoterol) programme, to new chemical entities for inhaled delivery (e.g. MARKET TRENDS Aesica’s development programmes). The majority of these clinical programmes are Pulmonary drug delivery can offer signif- aimed at treating respiratory based illnesses Dr Conrad Winters icant advantages over other administration such as asthma and chronic obstructive pul- Director, Drug Product Development routes. Compared with parenteral adminis- monary disease (COPD), cystic fibrosis and tration, it is a convenient and less intrusive pneumonia. However, there have been an T: +351 21 982 9000 F: +351 21 982 9388 Preclinical Phase I Phase II Phase III Hovione Number of projects 196 28 2 1 Sete Casas 2674-506 Loures Portugal Figure 1: Dry-powder inhalation products in clinical development (Source: PharmaCircle, May 2013). www.hovione.com Copyright © 2014 Frederick Furness Publishing Ltd www.ondrugdelivery.com 3 Hovione increasing number of DPI products in clini- cal development that target non-respiratory indications. For example, in Type II diabe- tes, MannKind Corporation has filed a US NDA for Afrezza (inhalable insulin). One other major driver for DPI for- mulation development is compliance with the Montreal Protocol, which establishes a control over ozone-depleting gases and led to the replacement of the original CFCs in metered dose inhalers for HFAs (and HFCs).3,4 But the latter still constitute an environmental threat since both HFAs and HFCs are greenhouse gases and environ- mental concerns may lead to a phase down/ phaseout in pMDIs 4 and drive their conver- Figure 2: Carrier-based versus composite particle approaches: strengths and limitations. sion to DPI formulations, also contributing to the results of Figure 1. Other techniques for making micron- ibility (Exubera DPI from Pfizer). More sized particles involve direct particle forma- recently, Pulmospheres, based on solid foam TECHNOLOGY TRENDS tion from solution. In this field, spray drying particles prepared by SD of an emulsion, (SD) has emerged as a noteworthy approach have been employed for a DPI formulation Innovation in inhalation drug delivery for achieving the desired aerodynamic size, of tobramycin (TOBI Podhaler). has primarily been focused on two paral- morphology and, ultimately, powder flow.10 As summarised in Figure 2, these plat- lel pathways: the development of novel This technique is distinctly different from forms are challenging to develop given inhaler devices, and the improvement of milling, as particles are built up by spraying the simultaneous requirements of physical powder formulations.5 Although pulmo- the drug and excipients from a solution or stability and optimal aerodynamic per- nary delivery can be enhanced by designing emulsion into fine droplets that are after- formance. Conversely, the particle engi- more sophisticated inhalers (e.g. electronic wards dried in a chamber. Compared with neering and formulation are done in a synchronisation), such devices tend to be milling, SD can produce more spherical par- single step, overcoming potential uniform- complex and costly, and their practical- ticles that tend to be amorphous, conferring ity issues of traditional lactose-based DPI ity