Portal de Periódicos da CAPES

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9–11, 2015

2016; Mary Ann Liebert, Inc.; Volume: 29; Issue: 3 Linguagem: Inglês

10.1089/jamp.2016.ab01.abstracts

1941-2703

Inhalation and Respiratory Drug Delivery

Journal of Aerosol Medicine and Pulmonary Drug DeliveryVol. 29, No. 3 AbstractsFree AccessAbstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9–11, 2015Published Online:1 Jun 2016https://doi.org/10.1089/jamp.2016.ab01.abstractsAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Abstracts: Drug Delivery to the Lungs 2601. FACTORS AFFECTING DPI DEVELOPMENT FROM BENCH TO BEDSIDEde Boer A.H.Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen 9713 AV, The NetherlandsSummaryThe factors that influence product development depend, amongst other things, on the type of product, the economic situation, the state of the art technology and various social and cultural trends. In modern era, often not the specs and costs are the decisive factors for purchasing a product, but aspects like design and brand personality. One of the reasons for this is the abundance of products of the same type for the same purpose. In fact, this is the current situation for dry powder inhalers (DPIs) although the self-congruity concept seems more applicable to the doctors who prescribe the inhalers than to the patients who are using them. For the early DPIs from the 1960s and 1970s the driving factor for development was the necessity of having an alternative for cholofluorocarbon (CFC) containing metered dose inhalers (MDIs). An important factor affecting their design could have been the desire to improve pulmonary drug delivery compared to that from MDIs, but unfortunately this oportunity was missed. Instead, available technology like hard gelatin capsules and adhesive (‘ordered’) mixtures were used and lung deposition remained more or less the same as from MDIs (only approx. 10% of the dose). After the capsule (and multi-dose reservoir) DPIs became more widely accepted and patents on inhaled drugs expired, consulting groups and generic manufacturers became more and more involved in the emerging DPI market, purely on an economic basis. This does not mean that there have not been developments yet aiming at improvement of the therapy with DPIs and various future applications may give a new boost to using new technology for dry powder inhalation.02. CHARACTERIZATION OF THE NANOSTRUCTURE, CRYSTALLINITY AND SPECIFIC SURFACE OF LACTOSE BASED INHALER POWDERS: SMALL-AND WIDE-ANGLE X-RAY SCATTERING (SWAXS) STUDIESWahl Verena1, Zimmer Andreas2, Khinast Johannes1,3, Paudel Amrit1, and Laggner Peter41Research Center Pharmaceutical Engineering, Inffeldgasse 13, Graz, 8010, Austria2Karl Franzens University of Graz, Institute of Pharmaceutical Science, Universitätsplatz 1, Graz, 8010, Austria3Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, Graz, 8010, Austria4Bruker AXS, Angelo-Eustacchio Gasse, Graz, 8010, AustriaSummaryThe aim of this work was to implement simultaneous the small- and wide- angle X-ray scattering (SWAXS) technique in the characterization of dry powder inhaler (DPI) carriers and formulation. SWAXS data were used to identify changes in crystallinity and inner structure (specific surface) of diverse inhalable lactose micro-particles originating from particle surface manipulation process. During the wet surface processing of carrier material a high amount of fines were produced identified as a mixture of α-lactose monohydrate and anhydrous lactose by a detailed analysis via SWAXS. Furthermore, to envisage the impact of environmental factors relevant to the processing, packaging and storage on the formulation attributes and performance selected lactose based commercial DPI formulations were exposed to accelerated storage conditions and microstructural evolution was investigated by SWAXS at regular time intervals. It was shown that during the storage of two commercial DPI products at different relative humidities, the specific surface of the formulation decreased significantly while no differences in the crystallographic pattern were noticeable. To prove the results, complementary techniques were implemented in the study (e.g. differential scanning calorimetry). Combined small- and wide- angle X-ray scattering seems to be a promising technique to identify changes in the particulate and the solid-states of DPI formulations and to predict physical stability.03. DEVELOPMENT OF MANNITOL-BASED COMPOSITE PARTICLES BY SPRAY DRYING: UNCOVERING THE CRITICAL PROCESS PARAMETERSCosta Eunice, Maia Filipa M., Campos Susana, and Neves FilipeHovione FarmaCiencia, SA, Sete Casas, 2674-506 Loures, PortugalMannitol has been extensively explored in dry powder inhalation (DPI), namely i) as an alternative to lactose monohydrate in carrier-based formulations, being a non-reducing sugar alcohol, ii) for the treatment of cystic fibrosis as an airway hydrating agent and iii) for bronchial provocation testing. Moreover, mannitol holds great potential for engineering DPI composite particle formulations by spray drying (SD), since it is highly crystalline after the process, ensuring enhanced physical stability.Although it is known that mannitol particle properties can be manipulated by adjusting SD parameters, few works can be found in the literature, especially on the field of respirable composite DPI formulations. For this reason, the current study reports the impact of SD parameters on mannitol particle size, morphology and solid state properties, aiming at optimal aerodynamic performance, using a design of experiments (DoE) approach. The best performing system was co-spray dried with nanoparticles of a model active pharmaceutical ingredient (API).The aerodynamic performance of the mannitol particles were significantly impacted by the drying temperature, since particle morphology changed substantially within the explored range, due to differences in crystallization kinetics. The feed solution concentration, contrarily to expectation, was not a very significant parameter and the best performing system considered an intermediate temperature/feed concentration. Moreover, inclusion of the nanoparticles did not change significantly the deposition profile, regardless of the API relative concentration.The illustrated development strategy allows a priori optimization of complex crystallizing composite particles, while balancing performance with process throughput. The resulting particles should be particularly suitable for dose-ranging studies, given its negligible dependence on the API load.04. MOVING FROM LOW SHEAR TO HIGH SHEAR BLENDING: A PREDICTABLE SCALE-UP OR A SOURCE OF UNCERTAINTY?Maia Filipa M., Lopes Isabel S., Palha Maria and Neves FilipeHovione FarmaCiencia, SA, Sete Casas, 2674-506 Loures, PortugalDry powder inhalation formulations include an excipient and an active pharmaceutical ingredient (API) which are present in different proportions and must be homogeneously blended. There are mainly two kinds of mixers available in the market to perform this operation: low-shear and high-shear mixers. The predominant mechanisms of both types of equipment are different and may impact the final mixture in terms of: (i) quality of mixing, (ii) aerodynamic performance and (iii) formulation stability. This work intends to compare the first two attributes stated above when using both types of blenders. For this purpose, six blends were produced in Turbula® (low-shear) and in Diosna® (high-shear) units and were evaluated for blend homogeneity and aerodynamic performance.The obtained results show that even though the blend uniformity was very similar for both processes, the quality of mixing given by the mixing index (MI) is higher for blends processed in the high-shear unit. Additionally, increasing mixing time and velocity did not have an impact on the quality of mixing, within the ranges explored in this work. Regarding aerodynamic performance, a decrease of the emitted dose (ED) and the fine particle dose (FPD) was observed for high-shear blends. Additional mixing steps on the high-shear blends proved to have an impact on the aerodynamic performance, since the optimum mixing time appears to have been achieved in the first additional step, after which a re-segregation may have occurred, with a detrimental impact on the in-vitro deposition profile. When moving from low-shear into high-shear blending, the observations drawn from this work should, therefore, be taken into consideration.05. INFLUENCE OF FINES ON COMMERCIAL LACTOSE CARRIERS AND THEIR DRY POWDER INHALATION PERFORMANCEHertel M1, Schwarz E2, Littringer E M2, Dogru M2, Scherließ R1, and Steckel H31Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany2Molkerei Meggle Wasserburg GmbH & Co. KG, Megglestr 6 - 12, 83512 Wasserburg am Inn, Germany3Deva Holding AS, Istanbul, TurkeyMany efforts have been made in the past to explain the beneficial effect of fines but the exact mechanisms how these fine lactose particles alter the performance of dry powder inhaler (DPI) formulations has remained unclear. In this study the influence of fines added to commercially available lactose carriers is investigated. For this purpose, two different-sized carriers were blended with different concentrations of fines and the model drug budesonide in different blending orders. All blends were prepared with a high shear mixer, which would make an upscaling possible, at different rotational speeds and mixing times. Afterwards the blends were tested with an inhaler device (Novolizer®) by using the Next Generation Pharmaceutical Impactor (NGI). The fine particle fraction (FPF), the fine particle dose (FPD) and the mass median aerodynamic diameter (MMAD) were then compared with the factors rotation speed, blending time, blending order and the amount of fines. It could be shown that all factors have an impact on the FPF and FPD. As an explanation all common postulated theories come into consideration. With the help of blending order results and SEM pictures the saturation of active sites, the function of the fines as a buffer during blending and the formation of drug-fines agglomerate could be proven. Overall, the great benefit of fines for commercial lactose carrier and their DPI performance could be shown in this work as well as the importance of a better understanding of the exact mechanism of their acting, in particular for the blending process.06. CHARACTERISATION OF PARTICLE ENGINEERED MANNITOL AS ALTERNATIVE CARRIERS IN DRY POWDER INHALATION FORMULATIONSRhein N1, Birk G2, and Scherließ R11Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany2Merck KGaA, Frankfurter Straße 250, 64293 Darmstadt, GermanyLactose is the typical carrier particle in carrier based powder blends for inhalation. Particle engineered Mannitol A and B are tested as potential alternative to the established carrier lactose in dry powder inhaler (DPI) formulations. Particle engineered Mannitol is a well-known product for direct compression in blends with low content of active pharmaceutical ingredients (API). Particle engineered Mannitol A and B are characterised with respect to their physico-chemical properties (particle size distribution, density, crystallinity, hygroscopicity). They are also as carrier material in interactive blends for DPIs and are investigated with respect to their suitability for inhalation (homogeneity and fine particle dose). It is shown that particle engineered Mannitol is a solid, crystalline and non-hygroscopic powder which shows a constant dosing from reservoir-based inhalers. The physical stability is an important factor for storage stability. Blends with an API content of 1.5 % exhibit a low relative standard deviation under 3% and an FPF of 24.68 % indicating that particle engineered Mannitol could be a good alternative carrier in DPI blends.07. SPACE CHAMBER DEVICES IN VITRO PERFORMANCE EVALUATION AT CONSTANT FLOWOliveira R F1, Teixeira S F C F2, Cabral-Marques H M3, and Teixeira J C F11CT2M R&D Centre, University of Minho, 4800-058 Guimarães, Portugal2ALGORITMI R&D Centre, University of Minho, 4800-058 Guimarães, Portugal3iMed. ULisboa R&D Centre, Universidade de Lisboa, 1649-003 Lisboa, PortugalBackground: The use of spacers is advisable for asthma treatment in younger patients (< 5 years). This work aims to evaluate such devices in terms of performance when compared against the use of pressurized Metered-Dose Inhaler (pMDI) solo.Methods: For that purpose an experimental in vitro assessment of four valved holding chambers (VHC) and one tubular spacer was made using a Multi-Stage Liquid Impinger at 60 L/min. The add-on devices were tested with Ventolin HFA-134a (salbutamol sulphate, as API), and the drug deposited in the setup was recovered with NaOH 0.01M. Solutions concentrations were estimated by UV-Vis spectrophotometry at 244 nm.Results: Results showed that the highest VHC mass deposition was found in the Volumatic®, while the valveless tubular spacer (i.e. Compact Space Chamber Spacer®) has the lowest deposition. Add-on devices throat deposition was found to be lower than the pMDI solo (≈45 μg). Only between the Compact Space Chamber® and the Space Chamber® were not found statistically significant differences in throat deposition (p > 0.05). The mass median aerodynamic diameter (MMAD) is lowest for the Volumatic® and highest (2.3 ± 0.1 μm) for the valveless tubular spacer (3.2 ± 0.3 μm), with statistical differences between the add-on devices (p < 0.001). The MMAD for VHCs with leaflets valve type showed no significant differences (p > 0.05). Fine particle mass (FPM) between the add-on devices showed no differences (p > 0.05). The highest FPM is provided by Volumatic® (36.5 ± 2.4 μg) and the lowest Compact Space Chamber Anti-static® (32.9 ± 3.2 μg). The pMDI solo emits lower FPM (29.3 ± 3.4 μg). The calculation of the coarse/fine/extra-fine particle fractions and coarse/fine/extra-fine ratios showed that all the add-on devices have similar performance results for all the calculated metrics, being within the reference values.Conclusions: Add-on devices provide the reduction of the coarse fraction of the pMDI plume and, subsequently, the reduction of the throat deposition. The existence (or not) of a valve, even the type of valve, has influence in the mass deposited inside the VHC and in the throat.08. APPLYING QBD PRINCIPLES IN EARLY DPI DEVELOPMENT: DESIGNING FOR ROBUSTNESS THROUGH DESIGN SPACE EXPLORATIONFernandes João V., Lopes Isabel S., and Neves FilipeHovione FarmaCiencia SA, Sete Casas, 2674-506 Loures, PortugalA major benefit of performing Design Space exploration as early as possible during Dry Powder Inhaler (DPI) development is the identification of optimal design parameters as well as the quantification of the robustness of such optimal design points. Design Space exploration is a cornerstone of Quality by Design (QbD) based approaches to pharmaceutical product development and its application to inhalation device development has been proposed.Within the context of the development of an enhanced version of the currently marketed TwinCaps® DPI with an enlarged powder cavity targeting effective high dosage drug delivery to the lungs, the current work reports an exploration of the Design Space considering the interactions of device, particle engineering and formulation design variables on key inhalation drug product performance attributes, such as Emitted Mass (EM) and Fine Particle Fraction (FPF5μm/EM). For that purpose, an experimental characterization of the Design Space defined by the i) device powder cavity outlet blockage σ, defined as the ratio between obstruction and total channel area (design parameter), ii) model drug particle size and iii) formulation fill weight, was performed using rapid prototyping technologies together with fast screening analytical methods.Results from the current Design Space exploration revealed that the selection of a device powder outlet blockage between 0.7 and 0.85 delivers a robust EM and FPF5μm/EM performance across the interval of particle size and formulation fill weight values evaluated.09. INVESTIGATION OF DRY POWDER INHALATION AEROSOLISATION PERFORMANCE AT DIFFERENT FLOW RATES FROM A CONVENTIONAL CAPSULE-BASED INHALER DEVICESaleem I Y1, Rajoli R KR1, and Diez F21School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK2Qualicaps Europe, S.A.U., Calle de la Granja 49, 28108 Alcobendas (Madrid), SpainBackground: Generally capsule-based dry powder inhalers (DPIs) are required to be used at a flow rate of 60 L/min to initiate removal and deaggregation of the drug from carrier for effective pulmonary deposition. This may not be appropriate for children or those with lung diseases. In addition, capsule-based DPI are intended for treatment over a 4-week period and storage conditions can influence the aerosolisation drug deposition, reproducibility of inhalation dose and treatment outcome.Methods: Inhalation grade lactose was blended with micronized salbutamol (50:1w/w) and filled (20 ± 1mg) in to size 3 hypromellose capsules stored at 22°C 40% RH for 4 weeks. Samples were tested using a 2-pin inhaler and aerosolised through a next generation impactor at a flow rate of 30 L/min (actuated for 8s) and 60 L/min (actuated for 4s) at weekly intervals for 4 weeks. Deposition of drug in the capsule, device and emitted dose (ED), fine particle dose (FPD), % fine particle fraction (FPF) and mass aerodynamic diameter (MMAD) were calculated.Results: Powder retention within capsules was higher at 60 L/min whereas it was higher in the device at 30 L/min (p < 0.05/Tukey). The ED, FPD, FPF was significantly greater at 60 L/min compared to 30 L/min at each time point (p < 0.05/Tukey). However, there was very little significant difference comparing each flow rate over time.Conclusion: Differences in results between the air flow rates at each weekly time points highlights the important relationship between inhalation, therapeutic dose, lung deposition and potentially therapeutic outcome.10. EFFECT OF THE BREATH-ACTUATED MECHANISM ON THE DISPERSION PERFORMANCE OF THE NEXTHALER®Mason F, Tweedie A, and Lewis D AChiesi Limited, Chippenham, Wiltshire, SN14 0AB, UKSummaryBackground: The innovative breath-actuated mechanism (BAM) within the NEXThaler® controls the dose release in response to pressure drop. The effect of the BAM on the dispersion performance from NEXThaler will be evaluated using in-vivo inhalation profiles.Methods: The dispersion performance of a 100μg/dose of Beclometasone Dipropionate (BDP) formulation was assessed, using in-vivo asthmatic inhalation profiles specific to the NEXThaler [1]. The three profiles differed notably from each other with peak inhalation flow rates of 45, 56 and 100 L min−1.Results: There was a noticeable reduction in dispersion performance when the BAM was removed from the NEXThaler device; 51% ± 3% compared to 37% ± 6% on average across all three profiles. Dose evacuation profiles demonstrate that without the presence of a BAM the dose is released at the same time, near the start of the inhalation, regardless of the inhalation profile (0.27 ± 0.01s). The NEXThaler Control BAM releases the dose only when a pressure drop of approximately 2kPa has been reached. Removal of the BAM causes the dose to be released into a slower airflow velocity, 9-11 L min−1 for the No-BAM device variant and 36-37 L min−1 for the NEXThaler Control. This may mean that larger carrier particles are less likely to impact within the device and could reduce the mass of fine active pharmaceutical ingredient (API) detaching from the carrier particles.Conclusion: Dispersion performance can be improved by moderating the release point of the dose; this is exemplified by the NEXThaler device which includes a BAM.11. EXTENDED COMPARISON BETWEEN GRAVIMETRIC IMPACTORS FOR THE EVALUATION OF COMPOSITE AND HIGH DOSAGE COMPOUNDS FOR INHALATIONLopes Isabel S., Palha Maria, Silva Sofia, and Neves FilipeHovione FarmaCiencia, SA, Sete Casas, 2674-506 Loures, PortugalThe development of dry powder inhalers (DPIs) and/or inhalation formulations is a laborious process which involves the determination of aerodynamic particle size distributions (aPSD), using full resolution impactors (i.e. Andersen Cascade Impactor (ACI) and the Next Generation Impactor (NGI)). Although developed to improve flexibility and precision, there is little information in the open literature regarding the benchmarking of the NGI with its predecessor, in their gravimetric form. Therefore, this work intends to compare both equipment and assess operational limits where the two techniques show good correlation. Additionally, characterization was also conducted with an abbreviated version of the NGI, the Fast Screening Impactor (FSI), to compare the results obtained via the three techniques (NGI, ACI, FSI) and, in this way, assess a potential full interchangeability.The obtained results show that good correlations were found between the two full resolution impactors (NGI, ACI) when using fill weights of 20 mg. On the other hand, high fill weights (of 80 mg) were found to have a detrimental effect on the correlation, mostly due to an overload of the NGI apparatus. When comparing the FSI results with the corresponding full resolution results, a good correlation was found, in general; however, some loss of accuracy was noticeable, which translated into a reduced discriminative power, if in the presence of formulations of similar performance. Finally, all obtained results suggest that the use of gravimetric impactors are well suited for evaluating powders with a highly cohesive and adhesive nature, like the ones considered during the current work.12. UNDERSTANDING THE IN VIVO IMPACT OF CARRIER-DRUG INTER-PARTICLE FORCES VIA ENGINEERED SURFACE MODIFICATIONS: AN IN SILICO INVESTIGATIONMercuri A1, Wu S1, Zellnitz S1, Salar-Behzadi S1, Bresciani M1, Khinast J1, and Fröhlich E21Research Center Pharmaceutical Engineering GmbH, Graz, 8010, Austria2Center for Medical Research, Medical University of Graz, Graz, 8010, AustriaEngineered modifications of carrier surfaces are used to control the inter-particle forces occurring between the carrier and the drug. In this way, tailoring of these forces enables the quantity of drug that can be delivered to the lungs to be modulated. In this work the impact of engineered modification of carrier-drug surface forces was investigated using glass beads as model carrier particles. Untreated and treated glass beads mixed with salbutamol sulphate were characterised in vitro for their aerodynamic performance. The fine particle fraction (FPF) for treated beads was 1.36 times higher than that for untreated beads. In vivo pharmacokinetic prediction of the surface modifications was investigated after using a validated in silico pharmacokinetic (PK) model. The simulation showed that Cmax for salbutamol released from surface engineered beads was 1.20 fold that of untreated beads. Both in vitro and in silico data showed that increasing the surface roughness of the carrier increased the fine particle delivery performance of the formulation.13. IN-VITRO STABILITY AND DEGRADATION OF PLGA AND PGA-CO-PDL MICROPARTICLES FOR PULMONARY DRUG DELIVERYOsman N1,2, Hilal M2, Mohamed S2, Dawood A2,3, Ritchie K1, Saleem I1, and Hutcheon G11School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK2Forensic Medicine & Clinical Toxicology Dept., Sohag University, Sohag, Egypt3Forensic Medicine & Clinical Toxicology Dept., Assuit University, Assuit, EgyptBackground: Aliphatic polyesters are widely used for drug delivery applications commonly poly (lactic-co-glycolic acid), PLGA. Their main drawbacks are the initial burst release and the resultant acidity at the site of drug action. A novel polyester; poly (glycerol adipate-co-w-pentadecalactone), PGA-co-PDL was synthesized and characterized to overcome these drawback. The study aim was to evaluate the stability and degradation of polymeric microparticles (MPs) prepared from PLGA and PGA-co-PDL under in-vitro pulmonary physiologic conditions as suspension in simulated lung fluid at 37 o C under axial rotation 15 rpm/ minute.Methods: MPs were formulated from PGA-co-PDL and PLGA by single emulsion method using Poly vinyl alcohol (PVA) as emulsifier. The MPs were characterized at specific time points for size, morphology and degradation features (by SEM), charge (By Zetasizer), pH (by pH meter) and molecular weight (By GPC).Results: PGA-co-PDL MPs showed slower changes of size decrease, degradation changes and acidity over PLGA MPs. The Molecular weight changes over time confirmed that PGA-co-PDL MPs were slower degrading than PLGA ones. The charge was negative due to PVA and the trend over time indicated PGA-co-PDL MPs were more stable than PLGA onesConclusion: PGA-co-PDL MPs carriers had slower degradation and more stability than PLGA MPs under the stated experimental conditions. They are suitable carriers for sustained release formulations.14. FORMULATION OF BIOLOGICS FOR INHALED AND NASAL DELIVERYParry Mark1, Solomon Derek1, Hammond Mark1, Ward David1, and Wake Ashleigh21Intertek Melbourn, Saxon Way, Melbourn, SG8 6DN, UK2Intertek Manchester, Hexagon Tower, Blackley, Manchester, M9 8GQ, UKBiopharmaceuticals are a vital part of modern pharmaceutical development however they are susceptible to a range of aggregation and degradation pathways which make the manufacture, processing and delivery of these products more challenging than more typical small molecules, with the majority of biologics being delivered parenterally. Inhaled and nasal delivery of biologic products allows for a more convenient method of administering compounds systemically, and also allows direct targeting of the respiratory system. The use of many biologics for long term disease management provides opportunities for repurposing of existing products for inhaled and nasal delivery to improve patient experiences and reduce complications from routine parenteral delivery. Examining excipient strategies and the impact of processing on biologics shows a variety of methods for managing the behaviour of biologic products, and examination of the common device technologies highlights the relative advantages of each type to fit with the physiological and commercial objectives. Examining the analytical techniques and the importance of understanding the activity and purity of the biologic product allows the development of a more suitable suite of tests to demonstrate the product safety and efficacy. Finally, review of real world case studies show how effective formulations can be developed by bringing together techniques for inhaled and biologic product development.15. THE APPLICATION OF BIOLOGICAL PRODUCT ANALYTICAL METHODOLOGIES TO SUPPORT THE DEVELOPMENT OF BIOLOGIC DRY POWDER INHALATION PRODUCTSWestern Karen, Childerhouse Nick, Munro Sandy, and Sefton SaraVectura Group plc, Vectura House, Bumpers Way, Chippenham, Wiltshire, SN14 6FH, United KingdomThe development of a biologic as a dry powder inhaler (DPI) product presents additional challenges to those already typically anticipated for a small molecule DPI (e.g. consistent and stable emitted dose (ED) and fine particle mass). One of the biggest challenges is ensuring that biologic potency and purity is maintained during the various manufacturing processes and afterwards, throughout the product shelf life and during drug delivery through the DPI. The application of a content assay method during development of a spray dried cytokine powder product identified that stabilising excipients were required in the feedstock to protect the cytokine from shear forces during spray drying. Development of a powder matrix for an immunomodulatory peptide required use of a purity (size exclusion chromatography (SEC)) method to detect degradation because a measure of activity alone by enzyme-linked immunosorbent assay (ELISA) would not have differentiated between different the stabilising properties of the powder matrices. A further case study for an immunomodulatory protein demonstrated how two different purity methods (SEC and non-reducing sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE)) may be required to detect aggregation. The final case study demonstrated how, during development pharmaceutics type studies to assess the DPI delivery system, the use of methods to both quantify biologic deposits on the device and assess the stability of these deposits using a biologic product analytical method to determine purity, provided information on formulation and delivery device optimisation. These investigations demonstrate how orthogonal biological product analytical methods have aided formulation/product development, manufacturing feasibility and product stability for potential biologic DPI products.16. A NEW DOSING SYSTEM TO FILL DRY POWDER INHALER DISCSSeyfang Karlheinz, Wolf Achim, and Adermann PhilippHarro Höfliger Verpackungsmaschinen GmbH, Helmholtzstr. 4, D71573 Allmersbach im Tal, GermanySeveral multi-unit dose dry powder inhalers on the market or in development contain injection-molded annular rings, which carry the single powder doses in closed cavities. These pockets can be round or oblong shaped and may be arranged in symmetric or asymmetric circles or even spirals. Current micro dosing systems like dosator, vacuum drum or membrane filler, which are suited to dose powders for inhalation, possess certain limitations when being used to fill inhaler discs, like insufficient robustness, inadequate output or limited flexibility regarding filling degree. Based on the membrane filling technology a new dosing system to fill such discs