Pharmaceutical Research

, Volume 34, Issue 1, pp 25–35 | Cite as

Aerosolization, Drug Permeation and Cellular Interaction of Dry Powder Pulmonary Formulations of Corticosteroids with Hydroxypropyl-β-Cyclodextrin as a Solubilizer

Research Paper

Abstract

Purpose

The purpose of this study was to assess the feasibility of hydroxypropyl-β-cyclodextrin as a solubilizer for the corticosteroids prednisolone and fludrocortisone acetate in dry powder inhalation formulations.

Methods

The dry particles were simultaneously produced and coated with nanosized L-leucine crystals using an aerosol flow reactor method. The aerosolization performances of carrier-free powders were studied using Easyhaler® and Twister™ at 2 and 4 kPa pressure drops over the inhalers. Drug permeation properties of the formulations were tested across a Calu-3 cell monolayer. Toxicity and reactive oxygen species induction were tested against Calu-3 and A549 cell lines.

Results

The hydroxypropyl-β-cyclodextrin in the powders promoted the dissolution of fludrocortisone the most, followed by that of prednisolone. Fine particle fractions were 52–70% from emitted doses which showed good repeatability with a coefficient variation of 0.9–0.17. In addition, hydroxypropyl-β-cyclodextrin enhanced the permeation of the corticosteroids. The powders showed no statistically significant toxicity nor reactive oxygen species induction in the tested cell lines.

Conclusions

This study demonstrated the preparation and function of fine powder formulations which combine improved dissolution of poorly soluble drugs with good aerosolization performance. These results are expected to promote particle engineering as a way to develop new types of therapeutic pulmonary powders.

KEY WORDS

coating cyclodextrin permeation poorly soluble drug pulmonary 

ABBREVIATIONS

BLPI

Berner-type low pressure impactor

CD

Cyclodextrin

CVED

The coefficient of variations of the powder emission

ED

Emitted dose

FLU

Fludrocortisone-21-acetate

FPF

Fine particle fraction

HP-β-CD

Hydroxypropyl-β-cyclodextrin

L

L-leucine

PRE

Prednisolone

ROS

Reactive oxygen species

Supplementary material

11095_2016_2035_MOESM1_ESM.pdf (286 kb)
ESM 1(PDF 285 kb)
11095_2016_2035_MOESM2_ESM.pdf (3.4 mb)
ESM 2(PDF 3495 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Faculty of MedicineUniversity of HelsinkiHelsinkiFinland
  2. 2.Division of Pharmaceutical Chemistry and TechnologyFaculty of Pharmacy, University of HelsinkiHelsinkiFinland
  3. 3.School of ScienceAalto UniversityAaltoFinland

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