Search

US-20260124325-A1 - Systems and Methods for Filling Vials with Gases

US20260124325A1US 20260124325 A1US20260124325 A1US 20260124325A1US-20260124325-A1

Abstract

The invention provides a method and apparatus for efficiently and accurately filling vials with gaseous materials such as a fluorinated gas, with or without concomitantly filling the vials with another liquid or solid material. Also provided is a filling system for simultaneously filling a vial with a gaseous material and a liquid material using the apparatus.

Inventors

  • Evan C. Unger
  • Daniel C. Evans
  • VaradaRajan Ramaswami

Assignees

  • Microvascular Therapeutics LLC

Dates

Publication Date
20260507
Application Date
20260102

Claims (12)

  1. 1 . A method for filling vials with a gaseous material, comprising: filling a single chamber vial with an aqueous suspension comprising lipids using an inner liquid-filling nozzle of a combined liquid/gas-filling nozzle simultaneously while injecting the gaseous material comprising a fluorinated gas into the headspace of the vial using an outer gas-filling nozzle of the combined liquid/gas-filling nozzle; and sealing the vial to securely contain the gaseous material inside the vial, wherein said method is performed without lyophilization or use of a lyophilization chamber.
  2. 2 . The method of claim 1 , wherein the fluorinated gas comprises a material selected from the group consisting of sulfur hexafluoride, perfluoropropane, perfluorobutane, perfluoropentane, and perfluorohexane.
  3. 3 . The method of claim 2 , wherein the fluorinated gas is perfluoropropane.
  4. 4 . The method of claim 1 , wherein the lipids in the aqueous suspension comprise dipalmitoylphosphtidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE), and. dipalmitoylphosphatidylethanolamine-monomethoxy-PEG (5,000) (DPPE-MPEG-5000).
  5. 5 . The method of claim 4 , wherein the aqueous suspension further comprises propylene glycol and sodium chloride.
  6. 6 . A single chamber vial pre-filled with a fluorinated gaseous material according to the method of claim 1 .
  7. 7 . The single chamber vial of claim 6 , wherein the fluorinated gaseous material is perfluoropropane.
  8. 8 . The single chamber vial of claim 7 , wherein the perfluoropropane comprises about 4 mg/mL to about 8 mg/mL therein.
  9. 9 . The single chamber vial of claim 7 , wherein the lipids comprise an amount of about 0.3 mg/mL to about 5 mg/mL therein.
  10. 10 . The single chamber vial of claim 7 , wherein the perfluoropropane therein comprises about 4 mg/mL to about 8 mg/mL and the lipids therein comprise an amount of about 0.3 mg/ml to about 5 mg/mL.
  11. 11 . A filling system for simultaneously filling a vial with a gaseous material and a liquid material, comprising: the combined liquid/gas-filling nozzle of claim 1 ; a sleeve attached to the inner liquid-filling nozzle to provide a seal on the single chamber vial to be filled; a pneumatic solenoid valve; one or more peristaltic pumps; and a decapper/capper.
  12. 12 . The filling system of claim 11 , further comprising a control system to control filling the single chamber vial.

Description

PRIORITY CLAIMS AND RELATED PATENT APPLICATIONS This continuation application claims the benefit of priority under 35 U.S.C. § 120 of pending application U.S. Ser. No. 18/436,953, filed Feb. 8, 2024, which is a continuation of application U.S. Ser. No. 16/093,617, filed Oct. 12, 2018, now abandoned, which is a national stage application under 35 U.S.C. § 371 of international application PCT/US2017/028257, filed Apr. 19, 2017, now abandoned, which claims benefit of priority under 35 U.S.C. § 119 (e) of provisional application U.S. Ser. No. 62/324,599, filed Apr. 19, 2016, now abandoned, the entire contents of all of which are incorporated herein by reference. TECHNICAL FIELDS OF THE INVENTION This invention generally relates to systems and methods for deploying gaseous materials. More particularly, the invention relates to apparatus and methods for efficiently and accurately filling vials with gaseous materials, such as a fluorinated gas, with or without concomitantly filling the vials with another liquid or solid material. BACKGROUND OF THE INVENTION Fluorinated gases have found many uses in the medical field, for example, to make ultrasound contrast agents. Definity®, comprised of phospholipid-coated perfluoropropane microbubbles, is an example of one such product. Definity® is manufactured by first preparing phospholipid suspension, which is aseptically filled into sterile lyophilization vials followed by exchange of headspace air above the liquid suspension for perfluoropropane gas using a lyophilization chamber. The final step of this manufacturing process is done by placing the vials containing the phospholipid suspension inside the lyophilization chamber, cooling and evacuating the atmosphere inside the chamber, and then releasing the octafluoropropane gas into the chamber. The vials, after they have been filled with gas, are stoppered, and the remaining gas inside the chamber (>>90%) is reclaimed. Such a method of filling gas is expensive due to the high cost of perfluoropropane gas ($1,940/kg) in addition to the cost associated with the use of lyophilizer itself. Additionally, perfluoropropane gas is heavier than air and may distribute unevenly in the lyophilization chamber, which can result in variations in the concentration of gas in the different vials due to their different positions within the lyophilization chamber. Thus, an ongoing need remains for a simpler, more efficient and economical system and method that greatly reduces waste of the fluorinated gas and ensures accuracy, reproducibility and uniformity of products. SUMMARY OF THE INVENTION The present invention is based in part on the discovery of novel apparatus and methods that allow efficiently and accurately filling of vials with gaseous materials, such as a fluorinated gas, with or without concomitantly filling the vials with another liquid or solid material. In one aspect, the invention generally relates to a method for filling vials with a gaseous material. The method includes: injecting the gaseous material into the headspace of a vial; and sealing the vial to securely contain the gaseous material inside the vial. In certain embodiments, the method further includes, prior to or simultaneous with injecting the gaseous material into the vial, filling the vial with a liquid material. In certain embodiments, the method includes evacuating the vial headspace prior to filling of the liquid and or/gaseous material. In another aspect, the invention generally relates to a vial pre-filled with a fluorinated gaseous material according to a method according to a method disclosed herein. In yet another aspect, the invention generally relates to a filling system for simultaneously filling a vial with a gaseous material and a liquid material, The system includes: a combined filling nozzle comprising a gas purging nozzle and a liquid filling nozzle; a sleeve attached to the filling nozzle providing a seal on the vial being filled; a pneumatic solenoid valve; one or more peristaltic pumps; a decapper/capper; and a control system. BRIEF DESCRIPTION OF THE DRAWINGS The invention will be better understood from a reading of the following detailed description taken in conjunction with the drawings in which like reference designators are used to designate like elements, and in which: FIG. 1 illustrates an experimental embodiment of a setup of the present invention. FIG. 2 illustrates an exemplary embodiment of a combined liquid/gas-filling nozzle. FIG. 3 illustrates an exemplary embodiment of a gas fill following vial headspace evacuation. FIG. 4 illustrates an exemplary embodiment of a filling system. FIG. 5 illustrates an exemplary embodiment of a filling system. FIG. 6 illustrates an exemplary embodiment of an array of multiple nozzles allowing multiple vials to be filled in parallel. DETAILED DESCRIPTION OF THE INVENTION The invention provides a filling system and related methods that deliver a gaseous material (e.g., a fluorinated gas) directly in