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Effect of carrier particle shape on dry powder inhaler performance
Luleå University of Technology, Department of Health Sciences, Medical Science.
Luleå University of Technology, Department of Health Sciences, Medical Science.ORCID iD: 0000-0002-6050-0432
Luleå University of Technology, Department of Health Sciences, Medical Science.ORCID iD: 0000-0002-0654-5410
University of Kent.
2011 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 421, no 1, p. 12-23Article in journal (Refereed) Published
Abstract [en]

he aim of this study was to characterise the aerosolisation properties of salbutamol sulphate (SS) from dry powder inhaler (DPI) formulations containing different carrier products. The difference in the elongation ratio (ER) of the different carriers was highlighted. Different set of carriers, namely commercial mannitol (CM), commercial lactose (CL), cooling crystallised mannitol (CCM), acetone crystallised mannitol (ACM) and ethanol crystallised mannitol (ECM) were used and inspected in terms of size, shape, density, crystal form, flowability, and in vitro aerosolisation performance using Multi Stage Liquid Impinger (MSLI) and Aerolizer® inhaler device. Solid-state and morphological characterization showed that CM product was in pure β-form having particles with smaller ER (CM: ER = 1.62 ± 0.04) whereas ACM and ECM mannitol particles were in pure α form with higher ER (ACM: ER = 4.83 ± 0.18, ECM: ER = 5.89 ± 0.19). CCM product crystallised as mixtures of β-form and δ-form and showed the largest variability in terms of particle shape, size, and DPI performance. Linear relationships were established showing that carrier products with higher ER have smaller bulk density (Db), smaller tap density (Dt), higher porosity (P), and poorer flow properties. In vitro aerosolisation assessments showed that the higher the ER of the carrier particles the greater the amounts of SS delivered to lower airway regions indicating enhanced DPI performance. Yet, DPI performance enhancement by increasing carrier ER reached a “limit” as increasing carrier ER from 4.83 ± 0.18 (ACM) to 5.89 ± 0.19 (ECM) did not significantly alter fine particle fraction (FPF) of SS. Also, carrier particles with higher ER were disadvantageous in terms of higher amounts of SS remained in inhaler device (drug loss) and deposited on throat. Linear relationship was established (r2 = 0.87) showing that the higher the carrier ER the lower the drug emission (EM) upon inhalation. Moreover, poorer flowability for carrier products with higher ER is disadvantageous in terms of DPI formulation dose metering and processing on handling scale. In conclusion, despite that using carrier particles with higher ER can considerably increase the amounts of drug delivered to lower airway regions; this enhancement is restricted to certain point. Also, other limitations should be taken into account including higher drug loss and poorer flowability.

Place, publisher, year, edition, pages
2011. Vol. 421, no 1, p. 12-23
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Other Health Sciences
Research subject
Health Science
Identifiers
URN: urn:nbn:se:ltu:diva-9484DOI: 10.1016/j.ijpharm.2011.09.010ISI: 000297612100002Scopus ID: 2-s2.0-81155122980Local ID: 8205df83-fb36-4dc4-8fc7-bf7ed15317dbOAI: oai:DiVA.org:ltu-9484DiVA, id: diva2:982422
Note
Validerad; 2011; 20110926 (ysko)Available from: 2016-09-29 Created: 2016-09-29 Last updated: 2018-07-10Bibliographically approved

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Kaialy, WaseemAlhalaweh, AmjadVelaga, Sitaram

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