Optimization of an electrostatically dosed dry powder inhaler

• US 6,571,793 B1
• Filed: 10/17/2000
• Issued: 06/03/2003
• Est. Priority Date: 09/21/2000
• Status: Expired due to Fees

• Current Assignee: Mederio AG
• Original Assignee: Microdrug AG
• Inventors: Nilsson, Thomas
• Primary Examiner(s): Dawson, Glenn K.
• Assistant Examiner(s): MENDOZA, MICHAEL G
• Application Number:
  US09/688,697
• Time in Patent Office: 959 Days
• Field of Search: 128/203.12, 128/203.15, 128/203.17, 128/203.26, 128/203.27, 128/202.25, 128/203.21, 128/200.14, 239/693, 239/708, 239/338
• US Class Current: 128/203.15
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 15/0083 Timers
• CPC Class Codes: A61M 15/02 with activated or ionised fluids, e.g. electrohydrodynamic [EHD] or electrostatic devices; Ozone-inhalators with radioactive tagged particles
• CPC Class Codes: A61M 2016/0039 in the inspiratory circuit
• CPC Class Codes: A61M 2202/064 Powder

Abstract

A method and a process are disclosed for optimizing an electrostatically dosed dry powder inhaler (EDPI) for utilization of a prepared pre-metered electro-dose consisting of a electro-powder. An arrangement is set-up for measuring parameters affecting a systemic delivery or local lung delivery of a pre-metered electro-dose from and DPI including analysis of dose de-agglomeration, particle size distribution as well as dose-to-dose variation together with pressures times and flows. A dry powder inhaler, DPI, is adjusted for a systemic or a local lung setting with respect to activation pressure and closing pressure having a DPI with a 20 to 60 liters/minute inhalation air flow for systemic delivery setting and 20 to 80 liters/minute for a local lung setting. Furthermore the de-agglomeration power is adjusted between 0.1 and 6 watts to be used in the DPI by optimizing the pressure drop and inhalation flow rate by changes to the mouthpiece and/or the device member and their relation to each other. The DPI activation pressure is further adjusted to a value between 0.5 and 4 kPa and closing pressure between 0.5 and 4 kPa to eliminate the low power at the start and end of the inhalation. The method and process then verify that the DPI meets the specifications set regarding de-agglomeration of power and opening and closing pressures together with timings within the DPI active time. Furthermore is verified that de-agglomeration difference, expressed in percent using an expression 100[1-de-agglomeration(Q_{1 kPa})/de-agglomeration(Q)], is not more than 50%. Finally if the DPI is not approved as an EDPI the tested DPI and/or electro-dose is further adjusted to check if the DPI can meet the specifications of an EDPI.

Claims

1. A method for optimizing an electrostatically dosed dry powder inhaler (EDPI) for utilization of a prepared pre-metered electro-dose consisting of an electro-powder, comprising the steps of

arranging a measurement set-up for measurement of parameters affecting a systemic delivery or local lung delivery of a pre-metered electro-dose from a dry powder inhaler (DPI) including analysis of dose de-agglomeration, particle size distribution as well as uniformity of dose together with pressures times and flows according to USP;

adjusting said DPI for a systemic or a local lung setting with respect to an activation pressure and a closing pressure having a DPI with a 20 to 60 liters/minute inhalation air flow for a systemic delivery setting and 20 to 80 liters/minute for a local lung setting;

adjusting a de-agglomeration power between 0.1 and 6 watts to be used in said DPI by optimizing a pressure drop and an inhalation flow rate by changes to a mouthpiece and/or a device member and their relation to each other;

adjusting said activation pressure between 0.5 and 4 kPa and said closing pressure between 0.5 and 4 kPa to eliminate low power at the start and end of the inhalation;

verifying that said DPI meets specifications set regarding the de-agglomeration power and said activation and closing pressures together with timings within an active time of the DPI;

verifying that a de-agglomeration difference, expressed in percent using an expression 100[1−

de-agglomeration(Q_{1 kpa}/de-agglomeration(Q)], is not more than 50%, where Q_{1 kPa} represents a pressure drop over the inhaler device reduced to 1 kPa and Q represents a reference pressure drop;

verifying that a uniformity of dose meets a uniformity standard; and

verifying and optimizing a not approved DPI by further adjusting said DPI and/or electro-dose to meet specifications of an EDPI.

2. The method according to claim 1, comprising the further step of using an instrument for a physical particle size measurement in the measurement set up.

3. The method according to claim 1, comprising the further step of pre-defining a dose fine particle fraction of electro-powder particle size to be 3 μ

m or less for a systemic delivery dose.

4. The method according to claim 1, comprising the further step of pre-defining a dose fine particle fraction of electro-powder particle size to be 5 μ

m or less for a localized lung delivery dose.

5. The method according to claim 1, comprising the further step of optimizing the de-agglomeration difference to be less than 25%.

6. The method according to claim 1, comprising the further step of optimizing the de-agglomeration difference to be less than 10%.

7. The method according to claim 1, comprising the further step of optimizing the uniformity of dose to meet 90 to 110%.

8. The method according to claim 1, comprising the further step of optimizing the uniformity of dose to meet 95 to 105%.

9. The method according to claim 1, comprising the further step of optimizing the dose de-agglomeration (DD3 μ

m) for deep lung delivery to be more than 25%.

10. The method according to claim 1, comprising the further step of optimizing the dose de-agglomeration (DD5 μ

m) for local lung delivery to be more than 25%.

11. The method according to claim 1, comprising the further step of optimizing the pressure drop over the mouthpiece and the device member compared to a total pressure drop over the inhaler to be greater than 50%.

12. The method according to claim 1, comprising the further step of optimizing a dissipative connection between a user and the DPI to eliminate electrical fields due to potential differences.

13. The method according to claim 1, comprising the further step of adjusting a dose delivery time in relation to a time for a user'"'"'s full inspiration by adjusting a length of a powder strip on a dosing member used.

27. The method according to claim 1, comprising a definition of a dose delivery time t_a to T_a for a local lung delivery of said electro-powder and a dose delivery time t_s to T_s for a deep lung delivery of said electro-powder out of a total inhalation time period t to T, whereby t_a>

t_s, T_s>

t_a and T_a>

T_s within a time span T−

t.

28. The method according to claim 1, having electrical dissipative properties in contact with a user made out of dissipative or conductive polymers comprising a further step wherein electro-conductive material used is obtained from materials selected from the group of materials consisting of silver powder, platinum powder, gold powder, stainless steel powder, antimony-doped tin oxide, and antimony-doped silica oxide, or is an X-doped silica where X is an adamantine semiconductor or an octahedral semiconductor, and wherein the conductive material and the plastic material for a dissipative or conductive combination of the device member has a specification presenting a surface resistance of 10³-10¹²Ω

, and a volume resistivity of 10³-10¹² ohm·

m.

14. A process for optimizing an electrostatically dosed dry powder inhaler (EDPI) for utilization of a prepared pre-metered electro-dose consisting of an electro-powder, comprising

an arrangement of a measurement set-up for measurement of parameters affecting a systemic delivery or local lung delivery of a pre-metered electro-dose from a dry powder inhaler (DPI) including analysis of dose de-agglomeration, particle size distribution as well as dose-to-dose variation together with pressures times and flows according to USP;

an adjustment of the DPI for a systemic or a local lung setting with respect to an activation pressure and a closing pressure having said DPI with a 20 to 60 liters/minute inhalation air flow for a systemic delivery setting and 20 to 80 liters/minute for a local lung setting;

an adjustment of a de-agglomeration power between 0.1 and 6 watts to be used in said DPI by optimizing a pressure drop and an inhalation flow rate by changes to a mouthpiece and/or a device member and their relation to each other;

an adjustment of the activation pressure between 0.5 and 4 kPa and the closing pressure between 0.5 and 4 kPa to eliminate a low power at the start and end of the inhalation;

a verification that the DPI meets specifications set regarding the de-agglomeration power and the activation and the closing pressures together with timings within an active time of the DPI;

a verification that a de-agglomeration difference, expressed in percent using an expression 100[1−

de-agglomeration(Q_{1 kpa}/de-agglomeration(Q)], is not more than 50%, where Q_{1 kPa} represents a pressure drop over the inhaler device reduced to 1 kPa and Q represents a reference pressure drop;

a verification that a uniformity of dose meets a uniformity standard; and

a verification and optimization of a not approved DPI by adjustment of said DPI and/or electro-dose to meet specifications of an EDPI.

15. The process according to claim 14, comprising a utilization of an instrument for a physical size measurement in the measurement set up.

16. The process according to claim 14, comprising a pre-definition of a dose fine particle fraction of electro-powder particle size to be 3 μ

m or less for a systemic delivery dose.

17. The process according to claim 14, comprising a pre-definition of a dose fine particle fraction of electro-powder particle size to be 5 μ

m or less for a localized lung delivery dose.

18. The process according to claim 14, comprising an optimization of the de-agglomeration difference to be less than 25%.

19. The process according to claim 14, comprising an optimization of the de-agglomeration difference to be less than 10%.

20. The process according to claim 14, comprising an optimization of the uniformity of dose to meet a value of 90 to 110%.

21. The process according to claim 14, comprising an optimization of the uniformity of dose to meet a value of 95 to 105%.

22. The process according to claim 14, comprising an optimization of the dose de-agglomeration (DD3 μ

m) for deep lung delivery to be more than 25%.

23. The process according to claim 14, comprising an optimization of the dose de-agglomeration (DD5 μ

m) for local lung delivery to be more than 25%.

24. The process according to claim 14, comprising an optimization of the pressure drop over the mouthpiece and the device member compared to a total pressure drop over the inhaler to be greater than 50%.

25. The process according to claim 14, comprising an optimization of a dissipative connection between the user and the DPI to eliminate electrical fields due to potential differences.

26. The process according to claim 14, comprising an adjustment of a dose delivery time in relation to a time for a user'"'"'s full inspiration by an adjustment of a length of a dose powder strip on a dosing member to be used.