title: EXUBERA: pharmaceutical development of a novel product for pulmonary delivery of insulin.
abstract: Development of a product for pulmonary delivery of insulin presented significant technology challenges for this first-in-class pharmaceutical product. These included developing (a) a chemically stabilized protein, (b) a dry powder formulation exhibiting required aerosol physical characteristics, (c) low-dose powder filling and packaging technology, and (d) a mechanical device for powder dispersal and reliable dosing to the patient. The insulin drug is formulated using a novel excipient combination to create a powder with a high glass transition temperature (Tg). The high Tg minimizes insulin mobility (thus reactivity), enabling ambient storage conditions. The formulation composition results in minimal hygroscopicity, where customized packaging produced product ruggedness to humidity. The formulated insulin powder is manufactured by spray-drying. This technology was further engineered to produce the desired reproducible powder characteristics with tight control over particle size and moisture content. A solution step prior to drying assures homogeneity and minimizes dependence on the physical form of the components. Novel low-dose filling and packaging technology reproducibly meters milligram quantities of microfine powder to meet stringent quality requirements for dose control. The technology for accurate, uniform, high-throughput metering of drug powders allows for automation and is scaleable for commercial operations. Finally, the mechanical device design provides powder deagglomeration and dispersion processes in a reusable dry powder inhaler with unique characteristics. The device was designed to rely on patient-generated compressed air as the energy source. A sonic discharge of air through the novel TransJector reproducibly extracts, deagglomerates, and disperses the inhalation powder. A clear holding (spacer-type) chamber allows for patient feedback via dose visualization, and separates powder dispersal from the inspiratory effort. The EXUBERA [Pfizer (New York, NY) and sanofi-aventis (Paris, France)] product provides insulin into the bloodstream with similar reproducibly and effectiveness as subcutaneous injections.
authors.affiliation: Nektar Therapeutics, San Carlos, California, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: White
authors.forename: David B
authors.initials: DB
authors.lastname: Bennett
authors.forename: Scot
authors.initials: S
authors.lastname: Cheu
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Conley
authors.forename: Donald B
authors.initials: DB
authors.lastname: Guzek
authors.forename: Steven
authors.initials: S
authors.lastname: Gray
authors.forename: John
authors.initials: J
authors.lastname: Howard
authors.forename: Richard
authors.initials: R
authors.lastname: Malcolmson
authors.forename: Joann M
authors.initials: JM
authors.lastname: Parker
authors.forename: Phil
authors.initials: P
authors.lastname: Roberts
authors.forename: Negar
authors.initials: N
authors.lastname: Sadrzadeh
authors.forename: Jacqueline D
authors.initials: JD
authors.lastname: Schumacher
authors.forename: Sangita
authors.initials: S
authors.lastname: Seshadri
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Sluggett
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Stevenson
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Harper
mesh_terms: D000280:Administration, Inhalation; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry*; D036501:Metered Dose Inhalers; D010316:Particle Size
chemical_list: C473734:Exubera; D007328:Insulin