Preservative free insulin formulations
Inventors
Patton, John S. • Patton, Ryan S. • Kuo, Mei-chang • Ivri, Yehuda
Assignees
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Publication Number
US-10076613-B2
Publication Date
2018-09-18
Expiration Date
Abstract
One embodiment describes an insulin formulation that is specifically adapted for aerosolization. The formulation includes a major amount of water and a minor amount of insulin. Further, the formulation is preservative free, without meta-cresol, cresol or phenol, to permit the formulation to be aerosolized using a vibrating aperture plate without substantial foaming of the insulin formulation.
Core Innovation
The invention relates to an insulin formulation specifically adapted for aerosolization. The formulation comprises a major amount of water and a minor amount of insulin, together with minor amounts of HCl and NaOH to support the formulation, and 2 to 4 Zn2+ per insulin hexamer. The formulation is preservative free.
A central aspect is producing an aerosolized spray using a vibrating aperture plate having a plurality of apertures and using an annular vibratable element that circumscribes the apertures. The formulation is held on a rear face of the aperture plate by gravity and the aerosolized spray exits a front face solely by vibration of the aperture plate. The spray is produced without substantial foaming of the formulation.
The document further characterizes aerosolization performance and spray properties for the preservative-free insulin formulation. It describes that, when aerosolized without substantial foaming, the formulation facilitates aerosolization of the formulation as an aerosolized spray, and it contrasts this with aerosolization that is slower for commercial preservative-containing insulins due to foaming.
Claims Coverage
The provided claims include one independent claim focused on a preservative-free insulin formulation adapted for aerosolization using a vibrating aperture plate without substantial foaming, with dependent claims refining composition and aerosol performance characteristics.
Preservative-free aerosolizable insulin composition with Zn2+ and foam-free vibrating aperture plate spraying
An insulin formulation comprising a major amount of water; a minor amount of insulin; a minor amount of HCl; a minor amount of NaOH; and 2 to 4 Zn2+ per insulin hexamer; wherein the formulation is preservative free thereby facilitating aerosolization as an aerosolized spray using a vibrating aperture plate with a plurality of apertures, and wherein the spray is produced without substantial foaming when held on a rear face by gravity and the aerosolized spray exits a front face solely by vibration that is vibrated using an annular vibratable element that circumscribes the apertures.
Droplet mean size range for the aerosolized spray
The insulin formulation wherein aerosolized droplets have a mean size between about 3 μm and about 8 μm.
Foam conversion tolerance during aerosolization
The insulin formulation wherein less than 3% of the formulation is converted to foam during aerosolization.
Vibrating aperture plate frequency, aerosolization volume, and time performance
An insulin formulation sprayed without substantial foaming from a vibrating aperture plate operating at 50–150 kHz, with up to about 200 μL of formulation, requiring less than 22 seconds to aerosolize at least 97%.
Human insulin concentration range
The insulin formulation wherein the human insulin concentration is about 100 IU/ml to about 1200 IU/ml.
Exclusion of specific preservatives
The insulin formulation that excludes meta-cresol, cresol, and phenol.
The claims cover a preservative-free insulin formulation with major water, minor insulin, minor HCl and NaOH, and 2 to 4 Zn2+ per insulin hexamer, configured for aerosolized spray generation by a vibrating aperture plate without substantial foaming. The dependent features further specify droplet size, foam conversion, frequency and throughput, insulin concentration, and exclusion of meta-cresol, cresol, and phenol.
Stated Advantages
Facilitating aerosolization of the preservative-free formulation as an aerosolized spray.
Producing the aerosolized spray without substantial foaming.
Documented Applications
Aerosolized delivery of insulin as an aerosolized spray using a vibrating aperture plate having a plurality of apertures, with the formulation held on a rear face by gravity and exiting a front face solely by vibration.
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