Aerosolization, drug permeation and cellular interaction of dry powder pulmonary formulations of corticosteroids with hydroxypropyl-β-cyclodextrin as a solubilizer

Ville Vartiainen, Luis M. Bimbo, Jouni Hirvonen, Esko I. Kauppinen, Janne Raula

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.
LanguageEnglish
Pages25-35
Number of pages11
JournalPharmaceutical Research
Volume34
Issue number1
Early online date7 Sep 2016
DOIs
Publication statusPublished - 1 Jan 2017
Externally publishedYes

Fingerprint

Permeation
Powders
Adrenal Cortex Hormones
Lung
Pharmaceutical Preparations
Toxicity
Reactive Oxygen Species
Dissolution
Fludrocortisone
Cells
Nebulizers and Vaporizers
Prednisolone
Aerosols
Leucine
Inhalation
Pressure drop
2-hydroxypropyl-beta-cyclodextrin
Monolayers
Pressure
Cell Line

Keywords

  • coating
  • cyclodextrin
  • permeation
  • poorly soluble drug
  • pulmonary

Cite this

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title = "Aerosolization, drug permeation and cellular interaction of dry powder pulmonary formulations of corticosteroids with hydroxypropyl-β-cyclodextrin as a solubilizer",
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{\circledR} 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.",
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author = "Ville Vartiainen and Bimbo, {Luis M.} and Jouni Hirvonen and Kauppinen, {Esko I.} and Janne Raula",
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Aerosolization, drug permeation and cellular interaction of dry powder pulmonary formulations of corticosteroids with hydroxypropyl-β-cyclodextrin as a solubilizer. / Vartiainen, Ville; Bimbo, Luis M.; Hirvonen, Jouni; Kauppinen, Esko I.; Raula, Janne.

In: Pharmaceutical Research, Vol. 34, No. 1, 01.01.2017, p. 25-35.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aerosolization, drug permeation and cellular interaction of dry powder pulmonary formulations of corticosteroids with hydroxypropyl-β-cyclodextrin as a solubilizer

AU - Vartiainen, Ville

AU - Bimbo, Luis M.

AU - Hirvonen, Jouni

AU - Kauppinen, Esko I.

AU - Raula, Janne

PY - 2017/1/1

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N2 - 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.

AB - 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.

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