Pharmaceutical Research

, Volume 27, Issue 5, pp 786–795

In Vitro Aqueous Fluid-Capacity-Limited Dissolution Testing of Respirable Aerosol Drug Particles Generated from Inhaler Products

  • Deepika Arora
  • Kumar A. Shah
  • Matthew S. Halquist
  • Masahiro Sakagami
Research Paper

DOI: 10.1007/s11095-010-0070-5

Cite this article as:
Arora, D., Shah, K.A., Halquist, M.S. et al. Pharm Res (2010) 27: 786. doi:10.1007/s11095-010-0070-5

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.

KEY WORDS

aerosolscascade impactordissolutioninhaled corticosteroidsinhalers

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

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Deepika Arora
    • 1
  • Kumar A. Shah
    • 1
  • Matthew S. Halquist
    • 1
  • Masahiro Sakagami
    • 1
  1. 1.Department of Pharmaceutics, School of PharmacyVirginia Commonwealth UniversityRichmondUSA