Ville Vartiainen1, Luis M Bimbo2, Jouni Hirvonen3, Esko I Kauppinen4, Janne Raula5. 1. Faculty of Medicine, University of Helsinki, Clinicum, P.O. Box 22, FI-00014, Helsinki, Finland. 2. Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Helsinki, Finland. luis.bimbo@helsinki.fi. 3. Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Helsinki, Finland. 4. School of Science, Aalto University, P.O. Box 15100, FI-00076, Aalto, Finland. 5. School of Science, Aalto University, P.O. Box 15100, FI-00076, Aalto, Finland. janne.raula@aalto.fi.
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.
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.
Authors: Janne Raula; Antti Rahikkala; Tuomas Halkola; Jenni Pessi; Leena Peltonen; Jouni Hirvonen; Kristiina Järvinen; Timo Laaksonen; Esko I Kauppinen Journal: Int J Pharm Date: 2012-11-28 Impact factor: 5.875
Authors: Francesca Ungaro; Roberta d'Emmanuele di Villa Bianca; Concetta Giovino; Agnese Miro; Raffaella Sorrentino; Fabiana Quaglia; Maria Immacolata La Rotonda Journal: J Control Release Date: 2008-12-25 Impact factor: 9.776