Abstract
Purpose
To develop a unique in vitro aqueous fluid-capacity-limited dissolution system for the kinetic assessment of respirable aerosol drug particles from inhaler products.
Methods
Aerosol particles of 5 inhaled corticosteroids (ICSs) from 7 inhaler products were collected in the aerodynamic 2.1–3.3 or 4.7–5.8 μm on the filter membranes using the Andersen cascade impactor. Each filter membrane was then placed onto the donor compartment of the Transwell® system, where addition of 0.04ml aqueous fluid initiated aerosol ICS dissolution and permeation across its supporting membrane at 37°C and ∼100% humidity.
Results
The % profiles of dissolution and permeation were apparent first-order or pseudo-zero-order, reaching varying 1.9–95.0% by 5 h. Their kinetics overall conformed to the ICS aqueous solubility. With increasing aerosol mass, however, the profiles decelerated, attributed to undissolved ICSs left by the limited dissolution fluid capacity. The profiles could be also product-specific, as beclomethasone dipropionate aerosols from QVAR® dissolved faster than those from VANCERIL®, whereas fluticasone propionate aerosols from two different inhaler products exhibited comparable profiles. The 2.1–3.3 μm aerosols dissolved faster than the 4.7–5.8 μm aerosols.
Conclusions
Aerosol ICS dissolution into the limited aqueous fluid volume differed kinetically due to ICS solubility and aerosol mass, size, formulation and/or generation.
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Abbreviations
- ACI:
-
Andersen non-viable Cascade Impactor
- ANOVA:
-
analysis of variance
- APCI:
-
atmospheric pressure chemical ionization
- API:
-
active pharmaceutical ingredient
- BD:
-
budesonide
- BDP:
-
beclomethasone dipropionate
- CFC:
-
chlorofluorocarbon
- DDW:
-
distilled deionized water
- DPI:
-
dry powder inhaler
- ESI:
-
electrospray ionization
- FN:
-
flunisolide
- FP:
-
fluticasone propionate
- HFA:
-
hydrofluoroalkane
- HPLC:
-
high performance liquid chromatography
- ICS:
-
inhaled corticosteroid
- LOQ:
-
limit of quantification
- MS:
-
mass spectrometry
- PBS:
-
phosphate-buffered saline
- pMDI:
-
pressurized metered dose inhaler
- PVDF:
-
polyvinylidene difluoride
- SD:
-
standard deviation
- TA:
-
triamcinolone acetonide
- US:
-
United States
- USP:
-
United States Pharmacopeia
- UV:
-
ultraviolet
- VCU:
-
Virginia Commonwealth University
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Acknowledgments
The authors are grateful to H. Thomas Karnes, Ph.D. (VCU School of Pharmacy, VCU-SOP) for allowing the use of HPLC-MS/MS for FP and BDP assays. This research was funded by the Medical College of Virginia Foundation and VCU-SOP. D.A. acknowledges financial supports from the International Foundation of Ethical Research and VCU-SOP during her graduate study.
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Arora, D., Shah, K.A., Halquist, M.S. et al. In Vitro Aqueous Fluid-Capacity-Limited Dissolution Testing of Respirable Aerosol Drug Particles Generated from Inhaler Products. Pharm Res 27, 786–795 (2010). https://doi.org/10.1007/s11095-010-0070-5
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DOI: https://doi.org/10.1007/s11095-010-0070-5