title: Laser-ablated nanofunctional polymers for the formulation of slow-release powders for dry powder inhalers: physicochemical characterization and slow-release characteristics.
abstract: Recently, dry powder inhalation (DPI) powders coated with nanometre-thin layers of biodegradable polymers, prepared using pulse laser deposition (PLD), have been evaluated as a slow-release formulation for DPI use, with the goal of improving pulmonary selectivity. This paper describes evaluation of the chemical stability of one potential polymer, poly lactic acid (PLA), during the ablation process, the resulting respirable properties and potential cytotoxicity of coated glucocorticoid powders, and the resulting sustained-release characteristics of PLA-coated glucocorticoids creating using PLD. Triamcinolone acetonide (TA) and budesonide (BUD) were used as two model glucocorticoids to determine pulmonary targeting (PT) in-vivo. The chemical stability of PLA was determined at various laser energy densities. The respirable fraction and the cytotoxicity of the micronized particles of TA and BUD, coated using optimum laser energy density, were determined. In-vitro dissolution profiles were generated for the coated/uncoated formulations and an ex-vivo receptor binding assay was used to determine PT in rats. Increasing laser energy density led to decreases in molecular weight and film density, and increases in degradation products, roughness and thickness of the film. The mean dissolution time of coated formulations of BUD was longer (4 h) than with the less lipophilic TA (2 h). This correlated well with a more pronounced pulmonary selectivity observed for coated BUD ex-vivo. Stability and the physical properties of the film correlated with the laser energy density. We observed a direct relationship between the dissolution rate of the uncoated and coated formulation and the degree of PT; however, physiochemical properties of the drug (e.g. lipophilicity) may also contribute to the improved PT.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Intira
authors.initials: I
authors.lastname: Coowanitwong
authors.forename: Vikram
authors.initials: V
authors.lastname: Arya
authors.forename: Gina
authors.initials: G
authors.lastname: Patel
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Kim
authors.forename: Valentin
authors.initials: V
authors.lastname: Craciun
authors.forename: James R
authors.initials: JR
authors.lastname: Rocca
authors.forename: Rajiv
authors.initials: R
authors.lastname: Singh
authors.forename: Günther
authors.initials: G
authors.lastname: Hochhaus
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D019819:Budesonide / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D016503:Drug Delivery Systems; D004355:Drug Stability; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000633:toxicity; D007834:Lasers; D008168:Lung / Q000378:metabolism; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000633:toxicity; D011208:Powders; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000008:administration & dosage*
chemical_list: D000336:Aerosols; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005938:Glucocorticoids; D011091:Polyesters; D011108:Polymers; D011208:Powders; D019344:Lactic Acid; C033616:poly(lactide); D019819:Budesonide; D014222:Triamcinolone Acetonide