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

Buttini, Francesca; Rozou, Stavroula; Rossi, Alessandra; Zoumpliou, Varvara; Rekkas, Dimitrios M.

doi:10.1016/j.ejps.2017.10.042

Cited by 51 publications

(25 citation statements)

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“…Usability and simplification of administration manoeuvres and procedures represent further features of DPIs [ 3 ]. Good inhalation performance from a DPI includes several aspects, such as reproducibility and adequate availability of the active ingredient at the site of action [ 4 ]. These aspects are related to the dispersibility of the powders during the inhalation act and the aerodynamic behaviour of the active pharmaceutical ingredient (API) particles, which are mainly related to particle size distribution and particle density.…”

Section: Introductionmentioning

confidence: 99%

Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance

et al. 2021

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The search for best performing carriers for dry powder inhalers is getting a great deal of interest to overcome the limitations posed by lactose. The aerosolization of adhesive mixtures between a carrier and a micronized drug is strongly influenced by the carrier solid-state properties. This work aimed at crystallizing kinetically stable D-mannitol polymorphs and at investigating their aerosolization performance when used in adhesive mixtures with two model drugs (salbutamol sulphate, SS, and budesonide, BUD) using a median and median/high resistance inhaler. A further goal was to assess in vitro the cytocompatibility of the produced polymer-doped mannitol polymorphs toward two lung epithelial cell lines. Kinetically stable (up to 12 months under accelerate conditions) α, and δ mannitol forms were crystallized in the presence of 2% w/w PVA and 1% w/w PVP respectively. These solid phases were compared with the β form and lactose as references. The solid-state properties of crystallized mannitol significantly affected aerosolization behavior, with the δ form affording the worst fine particle fraction with both the hydrophilic (9.3 and 6.5%) and the lipophilic (19.6 and 32%) model drugs, while α and β forms behaved in the same manner (11–13% for SS; 53–58% for BUD) and better than lactose (8 and 13% for SS; 26 and 39% for BUD). Recrystallized mannitol, but also PVA and PVP, proved to be safe excipients toward lung cell lines. We concluded that, also for mannitol, the physicochemical properties stemming from different crystal structures represent a tool for modulating carrier-drug interaction and, in turn, aerosolization performance.

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Section: Introductionmentioning

confidence: 99%

Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance

et al. 2021

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“…The Quality by Design approach, a GST-based framework, and its applications upon the development of a dry powder inhaler and its overall clinical performance along with the interactions of it are presented in [56]. The authors provide a review regarding the application of the aforementioned approach and point out the missing elements to holistically understand the interactions and success of a pharmaceutical product.…”

Section: ) Pharmacologymentioning

confidence: 99%

“…• Moreover, GST and its derivatives offer a vast field of hypotheses testing where researchers can explore and realize essential attributes, relationships and interactions in previously unknown environments, thus getting a new insight on these systems. Characteristically, [51] propose the BPS model to explore the relation between back pain and smoking among other variables, while [56] suggest a framework (Quality by Design) to enhance and alter the dry powder inhaler development, embracing all the necessary knowledge and not conforming strictly to guidelines. To tackle existing limitations and further enhance the positive aspects of GST in the healthcare field, we suggest a further integration of big data analytics and simulation models to understanding contemporary systems from a multi-perspective view.…”

Section: ) Positive Aspectsmentioning

confidence: 99%

A General Systems Theory Approach in Public Hearing Health: Lessons Learned From a Systematic Review of General Systems Theory in Healthcare

et al. 2020

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General Systems Theory (GST), as it was introduced by Karl Ludwig von Bertalannfy, had a significant, yet mostly unacknowledged influence on systems theory. The purpose of the current review is to highlight and assess the application of the aforementioned theory in the healthcare field and suggest a new approach to the public hearing healthcare sector. A systematic literature review has been conducted in the electronic databases of ScienceDirect, Pubmed and IEEEXplore covering the years of 2009-2019, following the PRISMA guidelines. The article selection was performed to identify GST-related frameworks in the healthcare field and was completed through a process of removing duplicates and non-available articles, analyzing the tittle and abstract, and then reviewing the full text of each selected article. In the final analysis, 47 studies were selected and were thoroughly analysed. Almost half of these articles showed a practical implementation of GST-inspired frameworks, following different types of research methodology. Analysis of these methodologies identified the limitations and positive effects of GST in the healthcare field. Although there is a significant number of references in GST in the healthcare field over the last 10 years, applications of it need to be further tested and explored before they are put into real-situation testing. Simulation models and evidence-based approaches on a micro-, meso-and macro-level of systems should be used to provide the contextual information needed for establishing GST as a driving force in the healthcare field. To this context, a paradigm of GST data framework applied to the hearing loss screening area is hereby presented and discussed. It is shown that a GST approach can be used to identify equilibria in all levels, to balance gain and prediction capacity over time and enhance public hearing health approaches for treatment and management strategies. INDEX TERMS General systems theory, hearing healthcare, systemic approach, systematic review, public hearing health.

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“…Запропоновано навіть уживати термін «небулайзерна система», котрий підкреслює необхідність сумісності небулайзера та препарату для досягнення оптимальної доставки аерозолю до легень. При заміні будь-якого з компонентів небулайзерної системи (пристрою чи препарату) характеристики доставки аерозолю значно змінюються [29,30], що може вплинути на біодоступність медикаменту.…”

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Investigation of the distribution of particles of drugs with the help of cascade impactor

Dobrianskyi¹,

Holyshkin²,

Los³

et al. 2020

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BACKGROUND. Successful nebulization is a result of joint usage of nebulizer and medication, which equally define availability and disposition of the active substance. Amount of the substance delivered by different nebulizer systems may differ in more than 10 times. OBJECTIVE. The aim of the study was to investigate the distribution of aerosol particles of drugs for inhalation manufactured by «Yuria-Pharm» under conditions of usage of Ulaizer Home. MATERIALS AND METHODS. We investigated Ulaizer Home nebulizer and medications for inhalation (Decasan, Lorde hyal, Nebufluson, Nebutamol) with the help of new generation impactor (“Copley Scientific Limited”, Great Britain). RESULTS AND DISCUSSION. Mass median aerodynamic diameter (MMAD) of Decasan particles was 4.878 µm, geometric standard deviation (GSD) – 1.72. MMAD of Lorde hyal particles was 3.194 µm, GSD – 1.556. Drop distribution for Nebutamol was alike the distribution for non-viscous aqueous solutions (MMAD – 5.363 µm, GSD – 1.924). For Nebufluson MMAD was 5.491 µm, GSD – 1.724. CONCLUSIONS. The delivery of the inhaled drug to the required area of the respiratory system is a key to successful nebulization. It directly depends on the parameters of the aerosol. The distribution of particles of drugs manufactured by «Yuria-Pharm» in case of nebulization using Ulaizer Home allows to deliver the required amount of drug to the predefined parts of the respiratory system.

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

Cited by 51 publications

References 50 publications

Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance

Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance

A General Systems Theory Approach in Public Hearing Health: Lessons Learned From a Systematic Review of General Systems Theory in Healthcare

Investigation of the distribution of particles of drugs with the help of cascade impactor

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