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      Influence of physical properties of carrier on the performance of dry powder inhalers

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          Abstract

          Dry powder inhalers (DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance. The purpose of this review is to summarize and illuminate how these factors affect drug–carrier interaction and influence the performance of DPIs.

          Graphical abstract

          The physical properties of carrier particles used in dry powder inhalers (DPIs) particularly their size, morphology/shape, and surface roughness play a significant role in determining DPI performance by influencing the adhesion and detachment of drug–carrier adhesive mixtures. However, it is difficult to completely understand how they influence DPI performance as they are interdependent.

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          Inhaling medicines: delivering drugs to the body through the lungs.

          John S. Patton, Peter Byron (2007)
          Remarkably, with the exception of anaesthetic gases, the ancient human practice of inhaling substances into the lungs for systemic effect has only just begun to be adopted by modern medicine. Treatment of asthma by inhaled drugs began in earnest in the 1950s, and now such 'topical' or targeted treatment with inhaled drugs is considered for treating many other lung diseases. More recently, major advances have led to increasing interest in systemic delivery of drugs by inhalation. Small molecules can be delivered with very rapid action, low metabolism and high bioavailability; and macromolecules can be delivered without injections, as highlighted by the recent approval of the first inhaled insulin product. Here, we review these advances, and discuss aspects of lung physiology and formulation composition that influence the systemic delivery of inhaled therapeutics.
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            The relationship between attractive interparticle forces and bulk behaviour in dry and uncharged fine powders

            A. Castellanos (2005)
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              Dry powder inhaler formulation.

              Martin Telko, Anthony J R Hickey (2005)
              A drug product combines pharmacologic activity with pharmaceutical properties. Desirable performance characteristics are physical and chemical stability, ease of processing, accurate and reproducible delivery to the target organ, and availability at the site of action. For the dry powder inhaler (DPI), these goals can be met with a suitable powder formulation, an efficient metering system, and a carefully selected device. This review focuses on the DPI formulation and development process. Most DPI formulations consist of micronized drug blended with larger carrier particles, which enhance flow, reduce aggregation, and aid in dispersion. A combination of intrinsic physicochemical properties, particle size, shape, surface area, and morphology affects the forces of interaction and aerodynamic properties, which in turn determine fluidization, dispersion, delivery to the lungs, and deposition in the peripheral airways. When a DPI is actuated, the formulation is fluidized and enters the patient's airways. Under the influence of inspiratory airflow, the drug particles separate from the carrier particles and are carried deep into the lungs, while the larger carrier particles impact on the oropharyngeal surfaces and are cleared. If the cohesive forces acting on the powder are too strong, the shear of the airflow may not be sufficient to separate the drug from the carrier particles, which results in low deposition efficiency. Advances in understanding of aerosol and solid state physics and interfacial chemistry are moving formulation development from an empirical activity to a fundamental scientific foundation.
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                Author and article information

                Contributors
                Xin Pan
                Chuanbin Wu
                Journal
                Journal ID (nlm-ta): Acta Pharm Sin B
                Journal ID (iso-abbrev): Acta Pharm Sin B
                Title: Acta Pharmaceutica Sinica. B
                Publisher: Elsevier
                ISSN (Print): 2211-3835
                ISSN (Electronic): 2211-3843
                Publication date PMC-release: 04 May 2016
                Publication date (Print): July 2016
                Publication date (Electronic): 04 May 2016
                Volume: 6
                Issue: 4
                Pages: 308-318
                Affiliations
                [a ]School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China
                [b ]Guangzhou Neworld Pharm. Co. Ltd., Guangzhou 51006, China
                [c ]Guangdong Research Center for Drug Delivery Systems, Guangzhou 510006, China
                Author notes
                [* ]Corresponding authors at: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China. Tel.: +86 20 39943427/+86 20 39943117; fax: +86 20 39943115.School of Pharmaceutical Sciences, Sun Yat-Sen UniversityGuangzhou510006China pxin_1385@ 123456163.com chunabin_wu@ 123456126.com
                Article
                Publisher ID: S2211-3835(15)30062-9
                DOI: 10.1016/j.apsb.2016.03.011
                PMC ID: 4951591
                PubMed ID: 27471671
                SO-VID: 8706b223-64eb-4451-8b65-aea33b1823da
                Copyright © © 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 17 November 2015
                Date revision received : 9 February 2016
                Date accepted : 2 March 2016
                Categories
                Subject: Review

                Keywords: api, active pharmaceutical ingredient,clf, coarse lactose fines,dae, aerodynamic diameter,dpi, dry powder inhaler,ed, emission dose,er, elongation ratio,flf, fine lactose fines,fpf, fine particle fraction,fr, flatness ratio,fshape, shape factor,fsurface, surface factor,mfv, minimum fluidization velocity,pdd, pulmonary drug delivery,pmdi, pressurized metered-dose inhaler,ro, roundness,carrier,particle size,morphology,surface roughness,performance,dry powder inhaler
                Data availability:
                Keywords: api, active pharmaceutical ingredient, clf, coarse lactose fines, dae, aerodynamic diameter, dpi, dry powder inhaler, ed, emission dose, er, elongation ratio, flf, fine lactose fines, fpf, fine particle fraction, fr, flatness ratio, fshape, shape factor, fsurface, surface factor, mfv, minimum fluidization velocity, pdd, pulmonary drug delivery, pmdi, pressurized metered-dose inhaler, ro, roundness, carrier, particle size, morphology, surface roughness, performance, dry powder inhaler

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