Abstracts from The Aerosol Society Drug Delivery to the Lungs 25Edinburgh International Conference Centre Edinburgh, Scotland, UK December 10–12, 2014

Abstract

Journal of Aerosol Medicine and Pulmonary Drug DeliveryVol. 28, No. 4 AbstractsFree AccessAbstracts from The Aerosol Society Drug Delivery to the Lungs 25Edinburgh International Conference Centre Edinburgh, Scotland, UK December 10–12, 2014Published Online:31 Jul 2015https://doi.org/10.1089/jamp.2015.ab02.abstractsAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Abstracts: Drug Delivery to the Lungs 2501. EFFICIENCY OF VALVED HOLDING CHAMBERS: EXPERIMENTAL FULL DOSE ASSESSMENTOliveira R F1, Silva M V1, Teixeira S F C F2, Cabral-Marques H M3, and Teixeira J C F11CT2M R&D Centre, University of Minho, 4800-058 Guimarães, Portugal2CGIT R&D Centre, University of Minho, 4800-058 Guimarães, Portugal3iMed.UL R&D Centre, Universidade de Lisboa, 1649-003 Lisboa, PortugalBackground: Asthma treatment by inhalation in young children, or elderly people with poor coordination, is advisable to be made through a Valved Holding Chamber (VHC) device when a pressurized metered-dose inhaler is prescribed. An analysis of the emitted dose (ED) from VHC devices is of utmost importance to infer about the best market option for a certain patient.Methods: A full dose apparatus was used to test the VHC devices at constant flow and under an inhalation profile. The devices were tested with Ventolin HFA-134a (salbutamol sulphate as API), and the drug deposited in the apparatus was recovered with NaOH 0.01M. Solutions concentrations were estimated by UV-Vis spectrophotometry at 244 nm.Results: At constant flow (26 L/min) results unveils that the ED ranking is the following: Vortex®>AeroChamber Plus®>NebuChamber®>SpaceChamber Plus®>OptiChamber Diamond®>A2A Spacer®>Volumatic®>Compact SpaceChamber Plus®. The inhalation profile lead to a different ED ranking: SpaceChamber Plus®>Compact SpaceChamber Plus®>NebuChamber®>AeroChamber Plus®>OptiChamber Diamond®>Vortex®>Volumatic®>A2A Spacer®.Conclusions: This work provided an insight into the ED efficiency of different VHCs. Device material, valve design and VHCs body length are the most relevant parameters. Evaluation of the emitted Fine Particle Mass is required to provide a meaningful comparison.02. CHEMICALLY SPECIFIC CHARACTERIZATION OF PARTICULATE IN INHALABLE DRUG PRODUCTS USING RAMAN AND LASER-INDUCED BREAKDOWN SPECTROSCOPYOlkhovyk O1, Vernall C2, Price R2 and Shur J21Gateway Analytical, 5316 William Flynn Highway, Gibsonia, PA, 15044, USA2University of Bath, Bath, BA2 7AY, UKBackground: The impact of foreign particulate and agglomerates on dissolution profile and permeability of the inhalable drug particles within the sites of action (i.e. patient's lungs) is critical. In this study, Raman Chemical Imaging (RCI) and Raman/Laser Induced Breakdown Spectroscopy (LIBS) spectroscopy were used to investigate the Active Pharmaceutical Ingredients (API) Particle Size Distribution (PSD), degree of particles aggregation and presence of foreign particulates in commercial inhalable products. Automated Raman/LIBS analysis was used to investigative the contamination issues and to establish the size and chemical makeup (metallic, organic or inorganic) of foreign particles.Methods: RCI method was applied to investigate the microstructure of com-mercial inhalable drug products in correlation to Cohesive-adhesive Balance (CAB) approach to colloid probe Atomic Force Microscopy (AFM). The SPE-Is raman.id+metal.ID system (Rap-ID, Berlin, Germany) was used to establish the size and chemical identification of foreign particulate.Results: By RCI/AFM analysis it is possible to establish the link between the microstructure and the dispersive mechanism of the formulation, which allows correlating adhesion properties of the particles with extend of different types of agglomerates. RCI can easily separate different chemical species or polymorphic/hydrate forms of the same chemical within single particle or aggregate for identification of polymorphic impurity/unwanted phase, whereas Raman/LIBS analysis provides information about quantity/chemical ID of any of the foreign particles.Conclusions: By using RCI in conjunction with automated Raman/LIBS analysis it is possible to identify presence of foreign particulate in the formulations and to analyze hundreds of foreign particles in hours. Such analysis may aid in understanding dispersion of the drug particles and inhalation product aerosolization performance without time-consuming impaction analysis testing or AFM analysis.03. PATIENT-CENTRED DEVICE CHARACTERIZATION: A NEW APPROACH TO STANDARDIZING REAL-LIFE CLINICAL USE AND MISUSE SCENARIOS FOR PRESSURIZED METERED DOSE INHALER PERFORMANCE TESTINGHassanien A1, Bruin R2, Sanders M2, Parisini I1, and Murnane D11University of Hertfordshire, Department of Pharmacy, College Lane, Hatfield, AL10 9AB, UK2Clement Clark International Ltd., Edinburgh Way, Harlow, Essex, CM20 2TT, UKSummaryThe pressurized metered dose inhaler (pMDI) is a versatile inhalation device that is well-accepted but used incorrectly by many patients. In order to support the development of pMDI therapies and add-on devices, there is an increasing awareness of the regulatory need to simulate the clinical use of inhalers in analytical methodologies, rather than rely on quality control laboratory tools. The aims of this study were two-fold: (1) to develop an experimental approach to simulate the ‘open-mouth’ inhalation technique recommended by many clinicians; and (2) to assess the impact of the open-mouth technique on aerosolization performance for a suspension pMDI of fluticasone propionate (FP, Flixotide 250 μg Evohaler). Employing the open-mouth set-up revealed a significant reduction in recovered dose (from 1177.1±18.5 to 363.9±77.3 μg FP) due to losses to the open environment. Although the open-mouth technique was associated with an excellent reduction in potential throat deposition, there was also a decrease in the fine particle dose from 92.1±1.4 μg to 65.2±22.2 μg (with good alignment of the inhaler with the vertical axis of the induction port) and 28.3±10.1 μg (with a subtle misalignment of the inhaler with the induction port). The open-mouth technique also resulted in high variability in the performance metrics, which raises concerns over the ability of patients to employ the technique correctly without compromising drug delivery performance. This work has identified the key experimental parameters required to examine the impact of the open-mouth inhalation practised by many patients and provides a benchmark for appropriate in vitro equivalence testing of inhalation devices.04. DETERMINATION OF FINE PARTICLE DOSE FOR ORALLY INHALED PRODUCTS (OIPs) BY ABBREVIATED IMPACTOR METHODOLOGIES: RESULTS FROM A MULTI-CENTRE STUDYNichols Steven C.1, Sandell Dennis2 and Mitchell Jolyon3 on behalf of the Impactor Sub-Team of the European Pharmaceutical Aerosol Group (EPAG)1OINDP Consultancy, Rugby, UK2S5 Consulting, Ekvägen 8, S-27562 Blentarp, Sweden3Jolyon Mitchell Inhaler Consulting Services Inc., 1154 St. Anthony Rd., London, N6H 2R1, CanadaSummaryBackground: Fine particle dose (FPD) is a critical quality attribute for OIPs. The abbreviated impactor measurement (AIM) concept can simplify its measurement, provided that FPD is comparable with the Pharmacopeial impactor measurement (PIM). This study compared FPD determined using AIM and PIM for 5 different dry powder inhaler (DPIs) and 2 pressurized metered dose inhaler (pMDI) products, one of which included a valved holding chamber (VHC) add-on device.Materials and Methods: Reference measurements of FPD were made following European Pharmacopoeial methods by each of 5 participants using either the full-resolution Andersen 8-stage non-viable impactor (ACI) or Next Generation Impactor (NGI). FPD was also determined for the same OIP(s) with an abbreviated impactor (fast screening impactor (FSI), fast screening Andersen (FSA) or reduced NGI (rNGI)). Each organization chose their own validated assay method(s) for the active pharmaceutical compound(s) involved. Ten replicate measurements were made by both AIM and PIM, with an aim to obtain a 90% confidence interval for the AIM/PIM FPD ratio of length 10%. The size limit for FPD varied from 4.4 to 5.0 μm aerodynamic diameter, depending upon flow rate, OIP studied and AIM apparatus; the corresponding FPD size limit for the PIM apparatus was selected to be 5 μm in accordance with the methodology in the European Pharmacopoeia.Results: The data fulfilled acceptance criteria for 9 of the 10 comparisons of FPD, in that the 90% confidence interval for the FPDAIM/FPDPIM ratio was contained in the predetermined 85 – 118% acceptance interval. The ratio [FPDAIM/FPDPIM] was on average 104% across all OIPs and apparatuses.Conclusions: The findings from this investigation support for equivalence of AIM and PIM for determination of FPD across a wide range of product types, OIP platforms and measurement techniques.05. DPI PERFORMANCE MODELLING USING AN INHALATION SIMULATOR AND OROPHARYNGEAL MODEL: A MORE PATIENT-RELEVANT APPROACH FOR DEVICE DEVELOPMENTLock Daniel James, Watkins Adam and Munro AlexanderVectura Limited, One Prospect West, Chippenham, Wiltshire, SN14 6FHSummaryThe performance of Dry Powder Inhalers (DPIs) is dependent on several factors including device design, formulation properties and the patient's inspiratory effort. Standard in vitro tests for DPIs employ cascade impactors with square-wave inhalation profiles; however DPI performance can be affected strongly by both peak inspiratory flow rate (PIFR) and acceleration rate.The use of more patient-relevant testing methodologies using Oropharyngeal (OP) models and more realistic inhalation waveforms is becoming more common as a consequence of efforts to improve in vivo/in vitro relationships (IVIVR) and to apply Quality by Design (QbD) principles to DPI development. Using an Alberta Idealised Throat (AIT), OP model in conjunction with an inhalation simulator, this study evaluated the aerodynamic particle size distribution of emitted doses from the Breo® ElliptaTM. Using a series of idealised inhalation profiles, a range of pressure drops and acceleration rates were applied in a Design of Experiment (DoE) based approach. Measurements of Fine Particle Mass (FPM), Impactor Sized Mass (ISM) and OP deposition indicated that the aerosolisation and delivery of drug to the impactor varied independently for each formulation and depended on the inhalation profile applied. Of the factors studied, acceleration rate was found to have a significant influence on FPM and ISM whereas the flow rate through the device was found to have no influence.It is proposed that the methodology described herein can yield an improved description of a DPI product's performance when tested under more realistic conditions, reflective of the influences brought to bear during actual patient use. Testing orally inhaled pharmaceuticals (OIPs) in this way may better inform QbD approaches to inhaled product development.06. INHALED NANOPARTICLES DEVELOP A COMPLEX PROTEIN CORONA OF BIOLOGICAL IMPORTANCEKumar Abhinav1, Bicer Elif Melis2, Pfeffer Paul3, Monopoli Marco4, Dawson Kenneth4, Blomberg Anders5, Behndig Annelie5, Dailey Lea Ann1, Forbes Ben1, and Mudway Ian21King's College London, Institute of Pharmaceutical Science, London SE1 9NH, UK2MRC-PHE Centre for Environment and Health, King's College London SE1 9NH, UK3MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London SE1 9RT, UK4Centre for BioNano Interactions, University College Dublin, Belfield, Dublin 4, Ireland5Department of Public Health and Clinical Medicine University of Umeå, Umeå, SwedenSummaryNanoparticle delivery systems are being designed as carriers for targeting drugs to the lungs, but when they deposit into lung lining fluid they are surface-modified by interaction with proteins and lipids. To date there is little information on the biomolecular corona that forms around nanoparticles in the lungs. Here we identify the protein corona that forms rapidly around nanoparticles in human lung lining fluid. Nanoparticles (silicon dioxide and polyvinyl acetate) were incubated for 1 h in human lung lining fluid and the hard corona was isolated. The proteins adhered to the particle surface were extracted and run through a 1-D SDS-gel. The bands of interest were cut and the proteins were extracted using trypsin digestion prior to injecting into the LC-MS/MS. Comparison with the Uniprot-SwissProt Human proteome database revealed enrichment around the particle surface of surfactant proteins, complement factors, immunoglobulins and other proteins with profound immunological actions, such as complement components. Surfactant proteins act as innate immunity proteins and opsonise microbes and particles and promote their clearance by phagocytosis by alveolar macrophages. Surfactant protein A coating has been shown to enhance the uptake of metal oxide nanoparticles as compared to metal oxide nanoparticles coated with albumin (the major plasma protein). This data improves our understanding of the behaviour of inhaled nanoparticles and informs the design of safe and effective nanomedicines such as those that aim to control the release of drugs in the lungs.07. COLLABORATIVE IPAC-RS INITIATIVES TO ADVANCE DEVICE DEVELOPMENTDundon Andy1, Wallace Roisin2 and Mannerstråle Fredrik31GlaxoSmithKline, Park Road, Ware, Hertfordshire, SG12 0DP, United Kingdom2Mylan, 775 Ramsgate Road, Sandwich, Kent, CT13 9NJ, United Kingdom3AstraZeneca, Västra Mälarehamnen 9, 151 85 Södertälje, SwedenSummaryThe purpose of this DDL presentation is to exemplify the work conducted by the International Pharmaceutical Aerosol Consortium on Regulations and Science (IPAC-RS, www.ipacrs.org) in the area of devices for orally inhaled and nasal drug products (OINDPs) so as to seek broader engagement from interested companies and individuals who wish to inform the regulatory framework within which companies must operate. The Device Working Group is just one of a number of strategic workstreams within IPAC-RS: 1. General (e.g., communications, global regulatory review outreach).2. Bioavailability, bioequivalence, in vitro in vivo correlations (e.g., population bioequivalence testing).3. CMC & Product Development (e.g., cascade impaction, delivered dose uniformity, leachables and extractables development paradigm).4. Delivery Systems (e.g., materials for OINDPs, devices, patient concordance).This presentation reports on the several initiatives spearheaded by the Device Group, such as streamlining and harmonizing quality requirements for devices, device change management, interpretation of the ICH Q8-9-10 risk management and quality-by-design (QbD) guidelines, patient's instruction for use, and similar issues.08. THE RISE OF mHEALTH: HOW TECHNOLOGY IS BEING USED TO SUPPORT RESPIRATORY PATIENTSFradley Georgina1, Bonam Matt2, and Brincat Mark11Exco InTouch, Unit 6, Wheatcroft Business Park, Nottingham, NG12 4DG, UK2AstraZeneca, Alderley Park, Macclesfield, SK10 4TF, UKWith the rising cost of healthcare worldwide, providers around the world are seeking new ways to address the challenge of caring for patients with chronic conditions. Advances in technology provide an ideal means to affect this change, with 96% of the global population having access to mobile devices a new market in mobile health ‘mHealth’ has emerged in recent years. This paper reviews the range of different solutions now offered by mHealth technologies and discusses how they can be leveraged to engage patients and facilitate long-term condition management. Several case studies are examined to illustrate how such programs have been implemented around the world to improve health outcomes for respiratory patients whilst providing clear return on investment for health payers, including the Florence program run by the UK National Health Service, the Easy Asthma Management program implemented by the Korea Society of Asthma and Allergy (KSAA) and the Care for Asthma via Mobile Phone program introduced in Taiwan. Finally the paper will discuss the Me&MyCOPD program which has been introduced in the UK by AstraZeneca as an integrated self-management program for patients with chronic obstructive pulmonary disease (COPD), breaking new ground in mHealth solutions by using a range of mobile and digital technologies to provide a personalised, truly mobile approach to monitor, support and empower patients to take control of their condition, utilising their own communication devices.09. PRESS-ON EFFECTS DURING BLENDING OF ADHESIVE MIXTURES FOR INHALATIONGrasmeijer F., Hagedoorn P., Frijlink H.W., and de Boer A.H.Department of Pharmaceutical Technology and BiopharmacyUniversity of Groningen, Groningen, The Netherlandsf.grasmeijer@rug.nlPress-on forces are thought to play an important role in the effects of drug content and added fine lactose particles on the dispersion behaviour of adhesive mixtures for inhalation. The mechanical stress experienced by the drug particles during the mixing process due to such forces can be assessed by a change in the apparent solubility of the drug in the mixture, as has previously been shown for salmeterol xinafoate (SX). The apparent solubility of SX was therefore used to study the effects of changes in the formulation variables mentioned on the occurrence and relevance of press-on forces. An increase in salmeterol content and the addition of ‘fine lactose fines’ (FLF, X50=1.95 μm) resulted in a lower apparent solubility of SX after prolonged mixing, whereas ‘coarse lactose fines’ (CLF, X50=3.94 μm) did not. These findings do not support the previously proposed hypotheses that higher fine particle contents increase the susceptibility of drug particles to press-on forces, and that CLF may act as a buffer between colliding particles to reduce the susceptibility of drug particles to press-on forces. However, it can be reasoned that a direct relationship between press-on effects and apparent solubility does not necessarily exist, especially when the carrier surface is covered by a multi-particulate layer. Therefore, the hypotheses cannot be conclusively rejected. It is shown, however, that the apparent solubility of salmeterol xinafoate is a useful measure for the characterisation of carrier-based dry powder inhalation formulations.10. USE OF VALVED HOLDING CHAMBERS WITHOUT PRE-CONDITIONING AND THE INFLUENCE OF ANTI-STATIC MATERIALSSuggett Jason1, Nagel Mark1, Doyle Cathy1, Schneider Heather1 and Mitchell Jolyon21Trudell Medical International, 725 Third St., London, N5V 5G4, Canada2Jolyon Mitchell Inhaler Consulting Services Inc., 1154 St. Anthony Rd., London, N6H 2R1, CanadaBackground: In recent years ‘anti-static’ Valved Holding Chambers (VHCs) have become more widely available. They enable use directly out of packet without pre-treatment, as pre-washing with detergent followed by drip-drying in air is time-consuming and not always followed. This laboratory study sought to investigate whether fine particle (<4.7 μm) drug delivery efficiency was similar from four commercially available VHCs, two of which were ‘anti-static’, the others being non-conducting, when pre-washing was not performed.Materials and Methods: Each VHC (n=3 or 5/group) was evaluated with Seretide® 250 pMDI (fluticasone propionate (FP)/25 salmeterol xinafoate (SX)), sampling the emitted aerosol at 28.3 L/min via an abbreviated Andersen impactor connected to a PhEur/USP induction port. A 5 s delayed inhalation was mimicked using a proprietary apparatus. Recovered FP and SX were assayed by validated HPLC-based methods.Results: The FPM<4.7μm for the non-conducting devices (Compact SpaceChamber Plus® and A2A™ Spacer) were greatly reduced compared with the anti-static devices with as low as 6% of the medication delivered in some cases compared to the best performing Anti-Static VHC. The two Anti-Static VHCs (AeroChamber Plus®Flow-Vu® Anti-Static VHC and OptiChamber® Diamond®) delivered consistently more medication as therapeutically beneficial FPM<4.7μm, however even for these two devices, the performance was not equivalent, with the former device exhibiting significantly higher values (1-way ANOVA, p<0.001).Conclusions: The results indicate that if pre-conditioning is not performed for non-conducting VHCs then there is likely to be greatly reduced medication delivered to the patient and therefore under-dosing until VHC conditioning occurs. The use of ‘anti-static’ VHCs improves the reliability of medication delivery from pMDI-VHC combinations, although there are still differences in performance, and other factors, such as chamber design can also affect the fine particle delivery. Care should be taken by prescribers in the selection of these devices.11. TIME-OF-FLIGHT METHODS FOR THE MEASUREMENT OF THE AERODYNAMIC PARTICLE SIZE DISTRIBUTION OF AEROSOLS FROM ORALLY INHALED PRODUCTS: POINTS TO CONSIDERMitchell JolyonJolyon Mitchell Inhaler Consulting Services Inc., 1154 St. Anthony Road, London, Ontario, N6H 2R1, CanadaBackground: Particle time-of-flight (TOF) methods rapidly determine the number-weighted aerodynamic particle size distribution (APSD) of aerosols from 0.3 to >20 μm aerodynamic diameter from all classes of orally inhaled product (OIP). Software is then used to calculate the mass-weighted APSD which should be equivalent to that obtained by the slower and substantially more complicated-to-use cascade impactor (CI) methods recommended in the pharmacopoeial compendia.Methods: We review this choice of techniques to obtain APSD-related information during the OIP life cycle, where there is regulatory freedom to do so. We also examine considerations concerning TOF- versus CI-based APSD determination for the different classes of OIP.Results: A serious drawback to TOF analysis has been the lack of a chemical assay for the active pharmaceutical ingredient(s) in the size-characterized particles. However, this limitation may be about to be overcome if TOF analysis is combined with single particle mass spectrometry, developed originally for bio-aerosol detection and size-categorization. The correlation of measures of clinically important fine particle mass (FPM) by TOF- and CI-based analyses can be achieved by the simultaneous measurement of this metric using a single-stage abbreviated impactor add-on supplied by the manufacturer of the most frequently encountered TOF analyzer.Conclusions: Users need to consider several potential sources of bias with TOF analysis, in particular distortion of droplets >5 μm diameter, deviations in particle density and shape from unit density microspheres, and increased statistical ‘noise’ associated with the number-to-mass weighting conversion.12. USE OF “SMARTPHONE” TECHNOLOGY TO CHARACTERISE AND AID DEVELOPMENT OF A STANDARDISED SHAKE FOR THE IN VITRO ANALYSIS OF MDIsLucke HelenCovance Laboratories Ltd., Otley Road, Harrogate, HG3 1PY, UKThe through-valve analysis of suspension based Metered Dose Inhalers (MDIs) is susceptible to differences between operators, resulting in biases and seemingly random variability, especially when undertaking though valve delivered dose testing and Aerodynamic Particle size Distribution (APSD) by Cascade Impaction (CI). Often, key sources of data variability are device handling factors such as the frequency and intensity of shaking applied to the can during analysis. The aim of this study was to assess whether accelerometer data captured from a standard domestic smartphone could be applied to develop a standardised shake for use by laboratory personnel in order to reduce this variability. This is desirable in order to increase confidence in results and to improve the likelihood of success when transferring methods between development laboratories and production sites and outsourcing partners. 5 different shakes were investigated and the total on impactor, throat dose and fine particle dose parameters were compared for differences through the life of the MDI and spread of results to determine the most favourable shake. A standardised shake was developed using characteristics of frequency and duration of shake determined from accelerometer data collected by a smartphone. This could be provided to trainees in the form of written instruction and/or video footage.13. THE INFLUENCE OF AMORPHOUS AMOUNTS IN ACTIVE PHARMACEUTICAL INGREDIENTS ON THE AERODYNAMIC PARTICLE SIZE DISTRIBUTION AND ON STORAGE STABILITYMüller T.1, Krehl R.1, Schiewe J.2, Weiler C.2, and Steckel H.11Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University, Grasweg 9 a, 24118 Kiel, Germany2Boehringer Ingelheim, Binger Straße 173, 55216 Ingelheim am Rhein, GermanySummaryBackground: There are changes of the carrier and active pharmaceutical ingredients (APIs) during the production of dry powder inhalers (DPIs). Standard pharmaceutical operations, like milling and blending, change specific particle characteristics which have a huge effect on drug delivery and product stability. Especially amorphous parts absorb water, re-crystallize and may lead to particle growth.Methods: In this study a hydrophilic and a hydrophobic model API were micronized to introduce different amorphous parts to the particle surface which were partially re-crystallized. After blending the mixtures were stored at 45%RH in a desiccator and the aerodynamic particle size distributions (APSD) were determined. The study target was to find out differences between the contrasting APIs, to evaluate the influence of amorphous parts and the storage stability over a six-month period.Results: Conditioning of the micronized APIs resulted in different amorphous amounts and similar particle sizes were received. The APSD showed contrasting results for both APIs. Very high fine particle fractions (FPFs) for the hydrophilic sample were determined at the beginning, which decreased over time. For the hydrophobic API the FPFs were very low and increased over time. The amorphous amounts showed a huge effect on dispersion behaviour and both mixtures showed differences in storage stability.Conclusions: This investigation showed that the control of amorphous content is of extreme importance because it influences the behaviour and the performance of DPIs. The storage stability showed especially for the hydrophobic CS blends an incalculable behaviour. The hydrophilic SBS led to constant FPFs after re-crystallisation. Therefore it is necessary that amorphous parts are determined and re-crystallised under controlled conditions.14. PULMONARY COMBINATION DRUG POWDERS COATED WITH SELECTED AMINO ACIDSRaula Janne1, Vartiainen Ville1, Pyysalo Jussi2, Brown David P.2 and Kauppinen Esko I.1,21Aalto University, School of Science, Espoo, Finland2Teicos Pharma Ltd., Espoo, FinlandSummaryCombination drug microparticles of beclomethasone and salbutamol sulphate were encapsulated and coated with amino acids L-leucine, L-valine and L-phenylalanine in the gas-phase in an aerosol reactor. The aim was to combine opposingly soluble drug materials into single particles and also to explore the influence of amino acid surface composition and texture on particle morphology and fine powder aerosolization. The amino acid coating was employed by partial vapor deposition on drug particle surfaces. Carrier-free powder aerosolization was studied using two different types of inhalers, Twister™ and Easyhaler® at two pressure drops, 2 kPa and 4 kPa, over the inhalers. The powder emissions from the inhalers were relatively good but the fine particle fraction (FPF) depended very much on particle integrity and sintering degree. The best results were obtained with the leucine coated samples when the particles were well separated whereas the worst results, particularly the FPF, was obtained with the phenylalanine coated samples due to a strong particle sintering i.e. fusing between particles. Moreover, the leucine rough coating performed the best aerosolization properties in terms of emission and fine particle deposition and also independency of applied pressure drop inhalation flow rate.15. DEFINING CRITICAL MATERIAL ATTRIBUTES OF MICRONISED LACTOSE IN DRY POWDER INHALER FORMULATIONSBansal Harsimran Singh1, Hebbink Gerald2, Shur Jagdeep1 and Price Robert11Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY, UK2DFE Pharma, Needseweg 23, Borculo, NetherlandsSummarySeveral studies have shown that the amount of fine lactose particles in dry powder inhaler (DPI) formulations is a key performance indicator of DPI drug product performance. The use of micronised lactose is however limited because of thermodynamic and chemical instability issues as a result of process-induced structural disorder upon micronisation. This disorder is present at the materials' surface in the form of thermodynamically unstable amorphous regions which undergo relaxation post micronisation.Investigations in relaxation of micronised lactose via conditioning at 20°C/70%RH at various time points are presented in this study. Physico-chemical changes were observed using cohesive-adhesive balance, isothermal perfusion calorimetry and particle size distribution measurements. The d10, d50, d90 and volume mean distribution (VMD) measurements increased with conditioning time. Perfusion calorimetry suggested a decrease in surface disorder through enthalpy of recrystallisation measurements decreasing with conditioning time. Force microscopy shows decreasing interfacial tensions between specific particles upon conditioning and agglomeration behavioural tendencies both in and out of formulation.Furthermore, in-vitro aerodynamic performance studies of specific formulations were studied using a next generation impactor. The conditioning of lactose fines affected the aerodynamic particle size distribution and mass mean aerodynamic diameter (M