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    Effect of carrier particle shape on dry powder inhaler performance.

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    Authors
    Kaialy, Waseem
    Alhalaweh, Amjad
    Velaga, Sitaram P
    Nokhodchi, Ali
    Issue Date
    2011-12-12
    
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    Abstract
    The 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 (D(b)), smaller tap density (D(t)), 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 (r(2)=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.
    Citation
    Effect of carrier particle shape on dry powder inhaler performance. 2011, 421 (1):12-23 Int J Pharm
    Publisher
    Elsevier
    Journal
    International journal of pharmaceutics
    URI
    http://hdl.handle.net/2436/576020
    DOI
    10.1016/j.ijpharm.2011.09.010
    PubMed ID
    21945739
    Type
    Journal article
    Language
    en
    ISSN
    1873-3476
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ijpharm.2011.09.010
    Scopus Count
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    Research Institute in Healthcare Science

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