DESC:FIELD OF THE INVENTION

The present invention is directed to an apparatus and method for collecting fine particles of inhalation drug products. Particularly described herein is an apparatus and method for collecting fine particle dose of powder inhalation products, wherein said apparatus can be received in the Next Generation Impactor (NGI) for testing the inhalation products.

BACKGROUND OF THE INVENTION

Next Generation Impactor (NGI) is a high-performance impactor to classify aerosol particle into size fractions for testing inhalation products such as metered-dose inhalers (MDI), and dry powder inhalers (DPI).

At present, there are no official dissolution test methods described applicable to inhaled products.

Based on a concept developed by Professor Jason McConville at the College of Pharmacy, University of Texas, the NGI dissolution cup and membrane holder incorporates a modification of the standard NGI collection cup.

The NGI dissolution cup (Copley Scientific, UK) is almost identical to a standard NGI cup except that it has a 50 mm removable insert in the impaction area where separated sample collects. The NGI dissolution cup fits directly into positions 2 through 7 in a standard NGI cup tray.

To collect a dose for dissolution testing the NGI is operated exactly as for routine aerodynamic particle size distribution (APSD) measurement, but with the dissolution cup installed at the stage of interest to allow capture of only the size fraction of interest rather than the entire emitted dose.

This allows the size-fractionated particles from an aerosol cloud to be collected and then tested in a conventional dissolution tester.

U.S. Pat. Publication No. 20090139352 A1 discloses a particulate matter collection apparatus which is connected directly to an inhaler device.

PCT Pat. Publication No. 2017051180 A1 discloses a modified Next generation Impactor (NGI) incorporating a collection device used to collect respirable material.

There is a need for an improved apparatus and method for collecting fine particle dose of inhalation products for performing the dissolution testing of these inhaled products without modifying the commercially available flow through apparatus such as NGI which is operated exactly as for aerodynamic particle size distribution (APSD) measurements.

SUMMARY OF THE INVENTION

One embodiment discloses fine particles collection system of inhaled drug for dissolution testing comprising: Next Generation Impactor (NGI) having NGI dissolution cup with an annual recess in the impaction area; and a particulate collection apparatus, which is received in the annual recess of NGI dissolution cup 3, wherein the Next Generation Impactor (NGI) is used without necessitating any structural modification

Some embodiments discloses the fine particles collection system, wherein the particulate collection apparatus comprises: a housing base part; a collapsible ring support; a collection part having a suction holes; a filter disposed on the collection part; and a suction device connected to the housing base part.
Some embodiments disclose particulate collection apparatus, wherein the housing base part has a hollow body defining an interior space, whereas the hollow body of the housing base part has rigid walls including a bottom wall, and a side wall, the bottom wall has a bottom flat surface generally in spherical or truncated hemispherical shape and having a peripheral edge bordering side wall, the side wall extending upwardly from the bottom wall and terminates at a top edge, a first rim flange extends radially inwardly around the top edge of the side wall to terminate in a open free edge that spaced apart from the top edge of side wall and further having top and bottom surfaces.

Some embodiments disclose particulate collection apparatus, wherein the housing base part has a side wall having outlet port to the suction device.

Some embodiments disclose particulate collection apparatus, wherein the collapsible ring support has a rigid body defining annular radial space having a bottom periphery and a top edge, a side wall extending between bottom periphery to top edge, a second rim flange that extends radially inwardly around the top edge of side wall to terminate in a open free edge which is spaced from the top edge of side wall and further having top and bottom surfaces, wherein the bottom periphery of collapsible ring support is aligned with open free edge of first rim flange of the housing base part and may be fixed to top surface of first rim flange.

Some embodiments disclose particulate collection apparatus, wherein the collection part has a flat top wall having an inner peripheral edge, a bottom flat wall having a outer peripheral edge, plurality of suction holes running between top wall and bottom wall, an annular side wall extending downwardly from the inner peripheral edge of top wall and terminates at bottom wall then extends radially outwardly to terminate in outer peripheral edge of bottom wall, wherein the bottom flat wall is concentrically aligned with second rim flange and may be fixed to top surface of second rim flange of collapsible ring support.
Some embodiments disclose particulate collection apparatus, wherein the suction holes of collection part provides the constant design volumetric flow rate of 60 LPM (Liter per minute) there through.

Some embodiments disclose a method for collecting fine particles dose of an inhalation drug for in-vitro dissolution testing, said method comprising: (i) providing a Next Generation Impactor having NGI dissolution cup with an annular recess in the impaction area; (ii) receiving a particulate collection apparatus in the annular recess of the NGI dissolution cup at any particular stage of NGI; (iii) connecting the inhaler to the NGI; (iv) connecting the suction device to particulate collection apparatus; (v) activating the inhaler to release a dose of drug product; (vi) activating the suction device; (vii) collecting the fine particles dose onto the filter disposed in the collection part of particulate collection apparatus and (viii) placing the filter in a dissolution tester, wherein the Next Generation Impactor (NGI) is used without necessitating any structural modification.

Some embodiments disclose the method for collecting fine particles dose of inhalation drug product, said method comprising: when the suction device is activated, the air current is generated which entrains aerosolized dose from the inhaler and drawn through suction holes of collection part, wherein particles collected on the filter disposed on the collection part.

Some embodiments disclose a method for collecting fine particles dose of inhalation drug product, wherein the fine mass of aerosolized drug collected at any particular stage is corresponding to any remaining stages of NGI.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure will now be described in further detail with reference to the accompanying schematic drawings, wherein
FIGURE 1 is a schematic view of NGI with a particulate collection apparatus;
FIGURE 2 is a perspective view of a particulate collection apparatus;
FIGURE 3 is a perspective view of a housing base part;
FIGURE 4 is a perspective view of a collapsible ring support;
FIGURE 5 is a top and bottom perspective views of a collection part.

DETAILED DESCRIPTION OF THE INVENTION

One embodiment discloses fine particles collection system 1 of inhaled drugs for dissolution testing as shown in FIGURE 1 comprising: Next Generation Impactor (NGI) 2 having NGI dissolution cup 3 and a particulate collection apparatus 5, wherein the said particulate collection apparatus 5 is received in the NGI 2.

The commercially available NGI dissolution cup 3 (Copley Scientific, UK) having annular recess in the impaction area for receiving removable insert and membrane holder.

In one embodiment, the particulate collection apparatus 5 is received in the annular recess 4 of NGI dissolution cup 3 in lieu of removable insert and membrane holder.

In one embodiment, the particulate collection apparatus 5 is received in Next Generation Impactor (NGI) 2 without necessitating any structural change or modification.

Referring to FIGURES 2-5, a particulate collection apparatus 5 comprising a housing base part 6; a collapsible ring support 7; a collection part 8 having suction holes 9; a filter 10 disposed on the collection part 8; and a suction device 11 connected to the housing base part 6.

The housing base part 6 has a hollow body defining an interior space, whereas the hollow body of the housing base part 6 has rigid walls including a bottom wall 12, and a side wall 13, the bottom wall 12 may have a bottom flat surface generally in spherical or truncated hemispherical shape and having a peripheral edge bordering side wall 13, the side wall 13 extending upwardly from the bottom wall 12 and terminates at a top edge 14, a first rim flange 15 extends radially inwardly around the top edge of the side wall 14 to terminate in a open free edge 16 that spaced apart from the top edge of side wall 14 and further having top and bottom surfaces. The housing base part 5 side wall 13 is having outlet port 17 to the suction device 11.

The collapsible ring support 7 is a rigid body defining annular radial space having a bottom periphery 18 and a top edge 19, a side wall 20 extending between bottom periphery 18 to top edge 19, a second rim flange 21 extends radially inwardly around the top edge 19 of side wall 20 to terminate in a open free edge 22 that spaced from the top edge 19 of side wall 20 and further having top and bottom surfaces, wherein the bottom periphery 18 of collapsible ring support 7 is aligned with open free edge 16 of first rim flange 15 of the housing base part 6 and may be fixed to top surface of first rim flange 15.

The collection part 8 is having a flat top wall 23 having an inner peripheral edge 24, a bottom flat wall 26 having a outer peripheral edge 27, plurality of suction holes 9 running between top wall 23 and bottom wall 26, an annular side wall 25 extending downwardly from the inner peripheral edge 24 of top wall 23 and terminates at bottom wall 26 then extends radially outwardly to terminate in outer peripheral edge 27 of bottom wall 26, wherein the bottom flat wall 26 is concentrically aligned with second rim flange 21 and may be fixed to top surface of second rim flange 21 of collapsible ring support 7. The housing base part 6; a collapsible ring support 7; and a collection part 8 may be fixed with each other by any suitable means, preferably by using adhesive substance.

The filter 10 is disposed on the collection part 8 top wall 23 above the suction holes 9. The filter is preferably a robust sintered metal filter that can withstand the vacuum force.

As filter there may be used any filter that is appropriate for retaining particles in the range of up to 5 µm, for example in the range of from 1 µm to 5 µm. For example, there may be used filters with pore size of up to 3 µm and having sufficient air permeability that will not result in a reduction of flow rate.

The filter may, for example, be selected from woven fabrics, nonwoven fabrics, meshes and air-permeable films. In some embodiments, the filter comprises a fabric formed from glass microfibers or from filaments of a polymeric material selected from polycarbonates, polyesters, polyolefins, polyamides (for example nylons), acrylics, acrylic copolymers, polyvinylchlorides and polyetheretherketones. Suitable polyolefins include, for example, polyethylene, polypropylene and ethylene and propylene copolymers with one or more other monomers.

Suitable glass microfibers include, for example, borosilicate glass may be used. Polymer filters of polyamide or of polyvinylchloride with a nominal pore size of 3µm or less are also widely commercially available.

In other embodiments, the filter comprises a metal mesh, for example, of stainless steel, which advantageously has a pore size of less than 3 µm. Other suitable materials include, for example, polymer films provided that they have a suitable level of air permeability

The outer diameter of collection part 8 is substantially similar to the diameter of annular recess 4 of NGI.

Particularly, the particulate collection apparatus is positioned below the NGI dissolution cup 3, wherein the collection part 8 of particulate collection apparatus 5 is received in the annular recess 4 of NGI dissolution cup 3. The tip clearance between the collection part 8 of particulate collection apparatus 5 and the annular recess 4 of NGI dissolution cup 3 may be between 1- 10 cm, the lesser gap minimizes the particles collection loss at the collection part 7.

Another embodiment provides a method for collecting fine particle dose of inhalation products, said method comprising: providing a Next Generation Impactor 2 having an annular recess 4 in the NGI dissolution cup 3; receiving a particulate collection apparatus 5 in the annular recess 4 of NGI dissolution cup 3 in lieu of sample collection insert; connecting the inhaler to the NGI 2; connecting the suction device 11 to particulate collection apparatus 5; activating the inhaler to release a dose of drug product; generating air current comprising aerosolized dose particles and passing through the particulate collection apparatus 5; and collecting the fine particle dose onto the filter 10 disposed in the collection part 8 of particulate collection apparatus 5.

To collect a fine particle dose of inhalation products for dissolution testing, the inhaler is connected to the induction port of NGI 2 which expels the aerosolized dose of the inhaler to the NGI 2 upon activation of the inhaler. The particulate collection apparatus 5 is positioned below the NGI dissolution cup 3 at the stage of interest, for example third stage. The suction device 11 generates air current; the aerosolized dose is entrained in an air current and is drawn through suction holes 11 of collection part 8, wherein the particles collected on the filter 10 disposed on the collection part 8. The air current is first passed the collection part 8, next into the annular radial space of collapsible ring support 7 and then finally through the interior space of housing base part 6. Once the collection is completed, the filter 10 may be removed from the collection part 8 and placed in a conventional dissolution tester.

Further, the side wall 25 of collection part 8 may comprise a plurality of rubber gaskets which may prevent air leakage during the particles collection at the collection part 5.

The particulate collection apparatus 5 providing the constant volumetric flow rate of 60 LPM by the suitable number of suction holes 9 in the collection part 8, for example about thirty suction holes 9, wherein particles collecting on the filter 10 medium substantially impede the flow of air there through.

The volumetric flow rate may be varied between 15- 100 LPM depending on the number of suction holes 9 in the collection part 8. The number of suction holes 9 is directly proportional to volumetric flow rate.

The collection of the entire dose at any particular stage is corresponding to any remaining stages of NGI 2.

The fine particle mass or fine particle fraction generated by orally inhaled drug products is of principal importance as this is directly delivered to the lungs. The in vitro characterisations of inhaled drugs like particle size, surface morphology and dissolution profile may consider as key product parameters. The particulate collection apparatus 5 provides an effective means of collecting the fine aerosolised mass in conjunction with the standard Next generation Impactor (NGI) for various in vitro analyses. The fine mass of aerosolized drug between 5 µm and 2.5 µm can be collected by attaching the particulate collection apparatus 5 at appropriate stages without disturbing the standard NGI 2. The particulate collection apparatus 5 is non invasive, robust and can be used for different volumetric flow rates.

Various modifications and variations to the above-described particulate collection apparatus can be made without departing from the scope of the present disclosure.
,CLAIMS:1. A fine particles collection system 1 of an inhalation drug product for in-vitro dissolution testing comprising: (i) a Next Generation Impactor (NGI) 2 having NGI dissolution cup 3 with an annual recess 4 in the impaction area; and (ii) a particulate collection apparatus 5, which is received in the annual recess 4 of NGI dissolution cup 3, wherein the Next Generation Impactor (NGI) 2 is used without necessitating any structural modification

2. The fine particles collection system 1 according to claim 1, wherein the particulate collection apparatus 5 comprises: a housing base part 6; a collapsible ring support 7; a collection part 8 having a suction holes 9; a filter 10 disposed on the collection part 8; and a suction device 11 connected to the housing base part 6.

3. The particulate collection apparatus 5 according to claim 2, wherein the housing base part 6 has a hollow body defining an interior space, whereas the hollow body of the housing base part 6 has rigid walls including a bottom wall 12, and a side wall 13, the bottom wall 12 has a bottom flat surface generally in spherical or truncated hemispherical shape and having a peripheral edge bordering side wall 13, the side wall 13 extending upwardly from the bottom wall 12 and terminates at a top edge 14, a first rim flange 15 extending radially inwardly around the top edge of the side wall 14 to terminate in a open free edge 16 that spaced apart from the top edge of side wall 14 and further having top and bottom surfaces.

4. The particulate collection apparatus 5 according to claim 2, wherein the housing base part 6 has a side wall 13 having outlet port 17 to the suction device 11.

5. The particulate collection apparatus 5 according to claim 2, wherein the collapsible ring support 7 has a rigid body defining annular radial space having a bottom periphery 18 and a top edge 19, a side wall 20 extending between bottom periphery 18 to top edge 19, a second rim flange 21 that extends radially inwardly around the top edge 19 of side wall 20 to terminate in a open free edge 22 which is spaced from the top edge 19 of side wall 20 and further having top and bottom surfaces, wherein the bottom periphery 18 of collapsible ring support 7 is aligned with open free edge 16 of first rim flange 15 of the housing base part 6 and may be fixed to top surface of first rim flange 15.

6. The particulate collection apparatus 5 according to claim 2, wherein the collection part 8 has a flat top wall 23 having an inner peripheral edge 24, a bottom flat wall 26 having a outer peripheral edge 27, plurality of suction holes 9 running between top wall 23 and bottom wall 26, an annular side wall 25 extending downwardly from the inner peripheral edge 24 of top wall 23 and terminates at bottom wall 26 then extends radially outwardly to terminate in outer peripheral edge 27 of bottom wall 26, wherein the bottom flat wall 26 is concentrically aligned with second rim flange 21 and may be fixed to top surface of second rim flange 21 of collapsible ring support 7.

7. The particulate collection apparatus 5 according to claim 2, wherein the suction holes 9 of collection part 8 provides the constant design volumetric flow rate of 60 LPM there through.

8. A method for collecting fine particles dose of an inhalation drug for in-vitro dissolution testing, said method comprising: (i) providing a Next Generation Impactor (NGI) 2 having NGI dissolution cup 3 with an annular recess 4 in the impaction area; (ii) receiving a particulate collection apparatus 5 in the annular recess 4 of the NGI dissolution cup 3 at any particular stage of NGI 2; (iii) connecting the inhaler to the NGI 2; (iv) connecting the suction device 11 to particulate collection apparatus 5; (v) activating the inhaler to release a dose of drug product; (vi) activating the suction device; (vii) collecting the fine particles dose onto the filter 10 disposed in the collection part 8 of the particulate collection apparatus 5 and (viii) placing the filter 10 in a dissolution tester, wherein the Next Generation Impactor (NGI) 2 is used without necessitating any structural modification

9. The method according to claim 8, wherein when the suction device 11 is activated, the air current is generated which entrains the aerosolized dose from the inhaler and drawn through suction holes 9 of collection part 8, wherein particles collected on the filter 10 which is disposed on the collection part 8.

10. The method according to claim 9, wherein the fine mass of aerosolized drug collected at any particular stage is corresponding to any remaining stages of NGI 2.