From inhaler to lung: clinical implications of the formulations of ciclesonide and other inhaled corticosteroids

Figures & data

Table 1 Desirable characteristics of an effective asthma ICS device

Robustness of the device	Under standard-use scenarios the device works well over a broad range of temperatures
Ease of use	The device is ready to use without any prior preparation such as shaking or priming when in constant use’ The device is small, portable and easy to handle by all patients within the indication; children, elderly and severely ill
Stability of formulation	Ideally the device will provide a formulation and container-closure-system ensuring physical and chemical stability over the shelf-life of the product
Cost efficiency	Low cost per dose to patient
Delivered dose	Accuracy and uniformity of each delivered dose is consistent over a range (slow or fast) of inspiration times

Abbreviation: ICS, inhaled corticosteroids.

Table 2 Effect of temperature on fine particle dose of CIC 160 μg inhalers (Takeda batch # 4BG009)

Temperature	Fine particle dose* (μg/shot)
	40°C	25°C	4°C	−10°C
Mean	102	101	100	103
Range (min–max)	90–119	87–108	82–107	82–116

Notes:

* Fine particle dose: total cumulative drug mass (ciclesonide) collected on the filter to stage 3 of the ACI. The effect of a range of temperatures (−10°C to 40°C) upon the fine particle dose was determined by ACI testing. The mass of CIC < 5 μm did not vary considerably in the temperature range examined. Nycomed: a Takeda company, data on file 2001.

Abbreviations: CIC, ciclesonide; ACI, Andersen cascade impactor.

Figure 1 Comparison of the reported MMAD of inhaled corticosteroids for the treatment of asthma.

Note: Data from^{12,17,19–21,50}
Abbreviations: DPI, dry powder inhaler; HFA, hydrofluoroalkane; MMAD, mass median aerodynamic diameters; pMDI, pressurized metered dose inhaler.

Figure 2 Aerodynamic particle size distribution of CIC pMDI, Batch No 4BGA001 (MMAD = 1.52 μm, fine particle dose = 121 μg) (Nycomed: a Takeda company, data on file 2001).

Abbreviations: CIC, ciclesonide; MMAD, mass median aerodynamic diameters; pMDI, pressurized metered dose inhaler.

Table 3 The relationship between particle size and particle penetration into the airways and stages of the Andersen cascade impactor (operated at 28 L/minute)

Stage	Particle size (μm)	Deposition in respiratory tract
0	9.00–10.00
1	5.80–9.00
2	4.70–5.80	Pharynx
3	3.30–4.70	Trachea and primary bronchi
4	2.10–3.30	Secondary bronchi
5	1.10–2.10	Terminal bronchi
6	0.65–1.10	Alveoli
7	0.43–0.65	Alveoli
Filter	<0.43

Copyright © 2000, WB Saunders Co, Ltd. Reproduced with permission from Cripps A, Riebe M, Schulze M, Woodhouse R. Pharmaceutical transition to non-CFC pressurized metered dose inhalers. Respir Med. 2000;94(Suppl B):S3–S9.¹⁷

Figure 3 Regional lung deposition of inhaled technetium-99m-labeled monodisperse albuterol aerosols. (A) 5 × 8 matrix was closely fitted to the krypton ventilation-scan lung boundary and superimposed on the posterior thorax aerosol deposition images, which was partitioned into a central zone, 2 × 3 matrix centered on the lung hilum; an intermediate zone, 3 × 5 matrix excluding the central zone; and a peripheral zone defined as the remaining lung field within the lung outline. (B) 1.5 μm, (C) 3 μm, and (D) 6 μm MMAD.

Reprinted with permission of the American Thoracic Society. Copyright © 2005 American Thoracic Society. Usmani OS, Biddiscombe MF, Barnes PJ. Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. Am J Respir Crit Care Med. 2005;172(12):1497–1504.²² Official journal of the American Thoracic Society.

Note: Red areas indicate regions of highest radioactivity, and black of least radioactivity.
Abbreviation: MMAD, mass median aerodynamic diameters.

Figure 4 Visual comparison of the spray plumes emitted from a CIC HFA-solution pMDI and FP administered as an HFA-suspension pMDI.

Note: Nycomed: a Takeda company, data on file, 2012.
Abbreviations: CIC, ciclesonide; FP, fluticasone propionate; HFA, hydrofluoroalkane; pMDI, pressurized metered dose inhaler.

MartinRJTherapeutic significance of distal airway inflammation in asthmaJ Allergy Clin Immunol2002109Suppl 2S447S46011842317

 PubMed Web of Science ®Google Scholar

CrippsARiebeMSchulzeMWoodhouseRPharmaceutical transition to non-CFC pressurized metered dose inhalersRespir Med200094Suppl BS3S910919679

 PubMed Web of Science ®Google Scholar

YangTTLiSWykaBKenyonDDrug delivery performance of the mometasone furoate dry powder inhalerJ Aerosol Med200114448749411791689

 PubMedGoogle Scholar

LeachCLBethkeTDBoudreauRJTwo-dimensional and three-dimensional imaging show ciclesonide has high lung deposition and peripheral distribution: a nonrandomized study in healthy volunteersJ Aerosol Med200619211712616796536

 PubMedGoogle Scholar

van den BergeMTen HackenNHTvan der WielEPostmaDSTreatment of the bronchial tree from beginning to end: Targeting small airways inflammation in asthmaAllergy2013681162623210509

 PubMed Web of Science ®Google Scholar

UsmaniOSBiddiscombeMFBarnesPJRegional lung deposition and bronchodilator response as a function of beta2-agonist particle sizeAm J Respir Crit Care Med2005172121497150416192448

 PubMed Web of Science ®Google Scholar