The application of Quality by Design framework in the pharmaceutical development of dry powder inhalers

Abstract This review aims in discussing the application of the Quality by Design (QbD) approach on the development of the Dry Powders Inhalers (DPIs). It starts with a thorough presentation of the Quality's concept evolution within the pharmaceutical sector and how this slowly adopted set of quality guidelines is now a major scientific and regulatory requirement. DPIs represent a type of delivery system where the system's thinking approach integrating the device, the formulation and the patient represent a major challenge to be met. Within this context this review points out the critical gaps in this optimization exercise and proposes a series of remedies in overcoming the obstacles when the system's parts are viewed alone and not as a whole. Statistical thinking and the corresponding tools are the means for successfully carrying out this purpose. QbD is not just another guideline to simply comply with. It is the ultimate scope of any pharmaceutical development effort, which is to fully understand and then consistently meet the patient's needs during the entire lifecycle of the product. QbD is focusing on delivering quality value to the patients without compromises in product's safety and effectiveness profile. Graphical abstract Figure. No caption available.

[1]  F. Buttini,et al.  Effect of Flow Rate on In Vitro Aerodynamic Performance of NEXThaler® in Comparison with Diskus® and Turbohaler® Dry Powder Inhalers , 2016, Journal of aerosol medicine and pulmonary drug delivery.

[2]  Maria E Donawa The evolving process of European combination product review, Part II. , 2008, Medical device technology.

[3]  Miryam Barad,et al.  Design of Experiments (DOE) , 2018 .

[4]  Francesco Polese,et al.  A Brief Review of Systems Theories and Their Managerial Applications , 2010 .

[5]  A. Ralph,et al.  Optimizing aerosolization of a high-dose L-arginine powder for pulmonary delivery , 2015 .

[6]  J. M. Juran Making real change: Building and applying knowledge for improvement , 1993 .

[7]  John E. Mills,et al.  Design of experiments in pharmaceutical process research and development , 2004 .

[8]  R. Ambrus,et al.  Development of a microparticle-based dry powder inhalation formulation of ciprofloxacin hydrochloride applying the quality by design approach , 2016, Drug design, development and therapy.

[9]  Marcos Llusa,et al.  Low-dose capsule filling of inhalation products: critical material attributes and process parameters. , 2014, International journal of pharmaceutics.

[10]  Jukka Rantanen,et al.  Raman spectroscopy in pharmaceutical product design. , 2015, Advanced drug delivery reviews.

[11]  Abhishek Singh,et al.  Spray drying formulation of amorphous solid dispersions. , 2016, Advanced drug delivery reviews.

[12]  Evdokia Korakianiti,et al.  Statistical Thinking and Knowledge Management for Quality-Driven Design and Manufacturing in Pharmaceuticals , 2011, Pharmaceutical Research.

[13]  P. Colombo,et al.  Spray dried amikacin powder for inhalation in cystic fibrosis patients: a quality by design approach for product construction. , 2014, International journal of pharmaceutics.

[14]  P. Colombo,et al.  Spray-dried amikacin sulphate powder for inhalation in cystic fibrosis patients: The role of ethanol in particle formation. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[15]  Jérôme Mantanus,et al.  Design space approach in the optimization of the spray-drying process. , 2012, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[16]  Lisa M. Law,et al.  Inhaler Errors in the CRITIKAL Study: Type, Frequency, and Association with Asthma Outcomes. , 2017, The journal of allergy and clinical immunology. In practice.

[17]  H. Frijlink,et al.  Dry powder inhalation: past, present and future , 2017, Expert opinion on drug delivery.

[18]  H. Smyth,et al.  Carrier-free high-dose dry powder inhaler formulation of ibuprofen: Physicochemical characterization and in vitro aerodynamic performance. , 2016, International journal of pharmaceutics.

[19]  Joseph Moses Juran Juran on Quality by Design: The New Steps for Planning Quality into Goods and Services , 1992 .

[20]  P. Colombo,et al.  Drug Delivery Strategies for Pulmonary Administration of Antibiotics , 2015 .

[21]  Y. Heyden,et al.  Raman spectroscopy as a process analytical technology (PAT) tool for the in-line monitoring and understanding of a powder blending process. , 2008, Journal of pharmaceutical and biomedical analysis.

[22]  Nicholas Moore,et al.  Chronic obstructive pulmonary disease exacerbation and inhaler device handling: real-life assessment of 2935 patients , 2017, European Respiratory Journal.

[23]  Svend Havelund,et al.  Quality by design - Spray drying of insulin intended for inhalation. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[24]  Nazrul Islam,et al.  Developing an efficient and reliable dry powder inhaler for pulmonary drug delivery--a review for multidisciplinary researchers. , 2012, Medical engineering & physics.

[25]  Jukka Rantanen,et al.  Engineering of an Inhalable DDA/TDB Liposomal Adjuvant: A Quality-by-Design Approach Towards Optimization of the Spray Drying Process , 2013, Pharmaceutical Research.

[26]  Neal G. Anderson,et al.  Design of Experiments (DoE) and Process Optimization. A Review of Recent Publications , 2015 .

[27]  R. Leggett,et al.  In Vitro Dosing Performance of the ELLIPTA® Dry Powder Inhaler Using Asthma and COPD Patient Inhalation Profiles Replicated with the Electronic Lung (eLung™) , 2015, Journal of aerosol medicine and pulmonary drug delivery.

[28]  J. Rantanen,et al.  Critical Solvent Properties Affecting the Particle Formation Process and Characteristics of Celecoxib-Loaded PLGA Microparticles via Spray-Drying , 2012, Pharmaceutical Research.

[29]  H. Chrystyn,et al.  NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma , 2014, Expert opinion on drug delivery.

[30]  Paolo Colombo,et al.  Design of experiments (DoE) in pharmaceutical development , 2017, Drug development and industrial pharmacy.

[31]  A H de Boer,et al.  A critical view on lactose-based drug formulation and device studies for dry powder inhalation: which are relevant and what interactions to expect? , 2012, Advanced drug delivery reviews.

[32]  Paul W. S. Heng,et al.  Process Analytical Technology: Application to Particle Sizing in Spray Drying , 2008, AAPS PharmSciTech.

[33]  Stavros N. Politis,et al.  The Evolution of the Manufacturing Science and the Pharmaceutical Industry , 2011, Pharmaceutical Research.

[34]  Edina Pallagi,et al.  New aspects of developing a dry powder inhalation formulation applying the quality-by-design approach. , 2016, International journal of pharmaceutics.

[35]  G. Box,et al.  On the Experimental Attainment of Optimum Conditions , 1951 .

[36]  H. Smyth,et al.  Implementation of design of experiments approach for the micronization of a drug with a high brittle–ductile transition particle diameter , 2017, Drug development and industrial pharmacy.

[37]  Waseem Kaialy,et al.  A review of factors affecting electrostatic charging of pharmaceuticals and adhesive mixtures for inhalation. , 2016, International journal of pharmaceutics.

[38]  J. Khinast,et al.  Development of a design space and predictive statistical model for capsule filling of low-fill-weight inhalation products , 2016, Drug development and industrial pharmacy.

[39]  M. Flament,et al.  Dry Powder Inhalers: Study of the Parameters Influencing Adhesion and Dispersion of Fluticasone Propionate , 2012, AAPS PharmSciTech.

[40]  B. Bergman,et al.  Exploring the epistemological origins of Shewhart’s and Deming’s theory of quality: influences from C.I. Lewis’ conceptualistic pragmatism. , 2009 .

[41]  D. Ziegler,et al.  Characteristics of a capsule based dry powder inhaler for the delivery of indacaterol , 2010, Current medical research and opinion.

[42]  Douglas C. Montgomery,et al.  Introduction to Statistical Quality Control , 1986 .

[43]  Roger Nosal,et al.  PQLI Key Topics - Criticality, Design Space, and Control Strategy , 2008, Journal of Pharmaceutical Innovation.

[44]  Holger Grohganz,et al.  Design of Experiments-Based Monitoring of Critical Quality Attributes for the Spray-Drying Process of Insulin by NIR Spectroscopy , 2012, AAPS PharmSciTech.

[45]  G. K. Raju,et al.  Understanding Pharmaceutical Quality by Design , 2014, The AAPS Journal.

[46]  H. Chrystyn,et al.  The Genuair® inhaler: a novel, multidose dry powder inhaler , 2012, International journal of clinical practice.

[47]  Svetlana Lyapustina,et al.  Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drug Products (OIPs): Workshop Summary Report. , 2010, Journal of aerosol medicine and pulmonary drug delivery.

[48]  Amit G Singal,et al.  A Primer on Effectiveness and Efficacy Trials , 2014, Clinical and Translational Gastroenterology.

[49]  M Hoppentocht,et al.  Technological and practical challenges of dry powder inhalers and formulations. , 2014, Advanced drug delivery reviews.

[50]  Da-Hong Gao,et al.  Optimization of the operating conditions of a lab scale Aljet mill using lactose and sucrose: A technical note , 2008, AAPS PharmSciTech.

[51]  Lawrence X. Yu Pharmaceutical Quality by Design: Product and Process Development, Understanding, and Control , 2008, Pharmaceutical Research.

[52]  W. A. Shewhart,et al.  Economic quality control of manufactured product , 1930 .

[53]  R. Price,et al.  Defining the Critical Material Attributes of Lactose Monohydrate in Carrier Based Dry Powder Inhaler Formulations Using Artificial Neural Networks , 2014, AAPS PharmSciTech.

[54]  F. Lavorini,et al.  Optimising Inhaled Pharmacotherapy for Elderly Patients with Chronic Obstructive Pulmonary Disease: The Importance of Delivery Devices , 2016, Drugs & Aging.

[55]  H. Chrystyn,et al.  Clarifying the dilemmas about inhalation techniques for dry powder inhalers: integrating science with clinical practice. , 2012, Primary care respiratory journal : journal of the General Practice Airways Group.

[56]  V. Pokharkar,et al.  Single step spray drying method to develop proliposomes for inhalation: a systematic study based on quality by design approach. , 2014, Pulmonary pharmacology & therapeutics.

[57]  R. Ambrus,et al.  Effect of polymers for aerolization properties of mannitol-based microcomposites containing meloxicam , 2013 .

[58]  Lawrence X. Yu,et al.  Applications of process analytical technology to crystallization processes. , 2004, Advanced drug delivery reviews.