APPENDIX-A: TSLI Data Using SET-A to D (2%W/W Drug Conc., 60L/Min, 10 S)
APPENDIX-A: TSLI Data using SET-A to D (2%w/w drug conc., 60L/min, 10 s)
Drug / Carrier / SET / ED (%) / FPFTD(%) / FPFED (%) / Drug / Carrier / SET / ED (%) / FPFTD (%) / FPFED (%)AS / SV-A / A / 77.0 / 14.2 / 18.5 / DSCG / SV-A / A / 75.4 / 38.3 / 50.7
AS / SV-A / A / 87.9 / 16.1 / 18.3 / DSCG / SV-A / A / 75.7 / 33.5 / 44.3
AS / SV-A / A / 83.7 / 13.9 / 16.6 / DSCG / SV-A / A / 73.3 / 28.9 / 39.4
AS / SV-A / B / 81.0 / 9.4 / 11.6 / DSCG / SV-A / B / 81.2 / 33.2 / 40.9
AS / SV-A / B / 84.0 / 11.9 / 14.1 / DSCG / SV-A / B / 83.6 / 35.0 / 41.9
AS / SV-A / B / 86.6 / 13.2 / 15.2 / DSCG / SV-A / B / 77.8 / 29.7 / 38.2
AS / SV-A / C / 92.1 / 9.1 / 9.9 / DSCG / SV-A / C / 91.0 / 34.0 / 37.3
AS / SV-A / C / 93.5 / 8.7 / 9.3 / DSCG / SV-A / C / 91.0 / 34.1 / 37.5
AS / SV-A / C / 91.0 / 11.9 / 13.0 / DSCG / SV-A / C / 87.9 / 32.1 / 36.5
AS / SV-A / D / 88.0 / 8.9 / 10.1 / DSCG / SV-A / D / 94.7 / 22.8 / 24.1
AS / SV-A / D / 93.4 / 6.7 / 7.1 / DSCG / SV-A / D / 92.7 / 22.8 / 24.6
AS / SV-A / D / 88.8 / 6.7 / 7.5 / DSCG / SV-A / D / 86.3 / 20.9 / 24.2
AS / SV-B / A / 77.8 / 23.4 / 30.1 / DSCG / SV-B / A / 79.0 / 43.6 / 55.2
AS / SV-B / A / 91.0 / 13.6 / 15.0 / DSCG / SV-B / A / 75.5 / 31.0 / 41.1
AS / SV-B / A / 88.8 / 12.6 / 14.2 / DSCG / SV-B / A / 75.4 / 32.6 / 43.2
AS / SV-B / B / 88.6 / 9.8 / 11.1 / DSCG / SV-B / B / 83.4 / 39.1 / 46.9
AS / SV-B / B / 93.5 / 9.1 / 9.8 / DSCG / SV-B / B / 81.4 / 34.8 / 42.8
AS / SV-B / B / 90.3 / 12.5 / 13.8 / DSCG / SV-B / B / 79.5 / 30.1 / 37.9
AS / SV-B / C / 93.8 / 11.1 / 11.9 / DSCG / SV-B / C / 91.9 / 33.7 / 36.7
AS / SV-B / C / 95.4 / 8.5 / 9.0 / DSCG / SV-B / C / 90.8 / 37.0 / 40.7
AS / SV-B / C / 95.6 / 10.3 / 10.7 / DSCG / SV-B / C / 89.4 / 36.1 / 40.4
AS / SV-B / D / 91.8 / 8.9 / 9.7 / DSCG / SV-B / D / 92.4 / 27.1 / 29.3
AS / SV-B / D / 96.2 / 5.7 / 5.9 / DSCG / SV-B / D / 91.2 / 25.8 / 28.3
AS / SV-B / D / 91.4 / 5.9 / 6.4 / DSCG / SV-B / D / 88.4 / 23.2 / 26.2
AS / ML-A / A / 81.2 / 45.4 / 56.0 / DSCG / ML-A / A / 71.5 / 39.6 / 55.4
AS / ML-A / A / 85.6 / 42.9 / 50.1 / DSCG / ML-A / A / 80.5 / 48.0 / 59.7
AS / ML-A / A / 83.8 / 40.3 / 48.1 / DSCG / ML-A / A / 79.5 / 42.4 / 53.3
AS / ML-A / B / 77.2 / 36.2 / 46.9 / DSCG / ML-A / B / 69.8 / 38.5 / 55.2
AS / ML-A / B / 73.6 / 35.2 / 47.9 / DSCG / ML-A / B / 71.3 / 35.9 / 50.4
AS / ML-A / B / 76.6 / 36.4 / 47.5 / DSCG / ML-A / B / 70.4 / 36.9 / 52.5
AS / ML-A / C / 88.3 / 31.4 / 35.6 / DSCG / ML-A / C / 85.7 / 34.4 / 40.1
AS / ML-A / C / 87.1 / 31.0 / 35.6 / DSCG / ML-A / C / 83.8 / 31.0 / 37.0
AS / ML-A / C / 85.0 / 28.6 / 33.7 / DSCG / ML-A / C / 83.8 / 33.3 / 39.8
AS / ML-A / D / 84.7 / 23.0 / 27.1 / DSCG / ML-A / D / 86.8 / 26.9 / 31.0
AS / ML-A / D / 80.7 / 17.7 / 21.9 / DSCG / ML-A / D / 81.0 / 18.4 / 22.7
AS / ML-A / D / 84.9 / 23.5 / 27.7 / DSCG / ML-A / D / 84.6 / 17.4 / 20.5
AS / ML-B / A / 80.2 / 27.4 / 34.1 / DSCG / ML-B / A / 82.6 / 47.3 / 57.2
AS / ML-B / A / 82.8 / 38.3 / 46.3 / DSCG / ML-B / A / 81.4 / 50.0 / 61.5
AS / ML-B / A / 76.3 / 36.3 / 47.6 / DSCG / ML-B / A / 79.0 / 41.7 / 52.7
AS / ML-B / B / 72.4 / 28.5 / 39.4 / DSCG / ML-B / B / 68.8 / 42.5 / 61.8
AS / ML-B / B / 69.6 / 35.5 / 51.0 / DSCG / ML-B / B / 67.1 / 39.4 / 58.7
AS / ML-B / B / 79.5 / 35.1 / 44.2 / DSCG / ML-B / B / 72.7 / 38.9 / 53.5
AS / ML-B / C / 81.5 / 17.5 / 21.5 / DSCG / ML-B / C / 85.3 / 39.2 / 46.0
AS / ML-B / C / 87.5 / 18.7 / 21.4 / DSCG / ML-B / C / 82.6 / 34.3 / 41.5
AS / ML-B / C / 85.4 / 26.2 / 30.7 / DSCG / ML-B / C / 83.1 / 37.0 / 44.6
AS / ML-B / D / 90.0 / 13.0 / 14.5 / DSCG / ML-B / D / 85.5 / 23.6 / 27.6
AS / ML-B / D / 86.5 / 16.3 / 18.8 / DSCG / ML-B / D / 88.7 / 23.8 / 26.9
AS / ML-B / D / 76.5 / 11.1 / 14.6 / DSCG / ML-B / D / 83.9 / 17.5 / 20.9
APPENDIX-A Con’d:TSLI Data using SET-A to D (2%w/w drug conc., 60L/min, 10 s)
Drug / Carrier / SET / ED (%) / FPFTD (%) / FPFED (%) / Drug / Carrier / SET / ED (%) / FPFTD (%) / FPFED (%)IPR / SV-A / A / 71.9 / 33.1 / 45.9 / FLUT / SV-A / A / 72.2 / 15.6 / 21.7
IPR / SV-A / A / 69.6 / 29.1 / 41.9 / FLUT / SV-A / A / 68.7 / 15.0 / 21.8
IPR / SV-A / A / 71.2 / 32.9 / 46.2 / FLUT / SV-A / A / 69.1 / 14.8 / 21.4
IPR / SV-A / B / 72.8 / 32.0 / 43.9 / FLUT / SV-A / B / 68.7 / 13.5 / 19.6
IPR / SV-A / B / 71.5 / 32.8 / 45.8 / FLUT / SV-A / B / 68.8 / 13.5 / 19.7
IPR / SV-A / B / 71.8 / 33.6 / 46.8 / FLUT / SV-A / B / 68.8 / 13.6 / 19.7
IPR / SV-A / C / 87.1 / 31.9 / 36.6 / FLUT / SV-A / C / 84.4 / 15.9 / 18.8
IPR / SV-A / C / 88.1 / 36.1 / 41.0 / FLUT / SV-A / C / 88.1 / 15.1 / 17.2
IPR / SV-A / C / 88.6 / 33.6 / 37.9 / FLUT / SV-A / C / 89.5 / 16.2 / 18.1
IPR / SV-A / D / 91.0 / 29.5 / 32.4 / FLUT / SV-A / D / 86.9 / 10.5 / 12.1
IPR / SV-A / D / 89.1 / 32.2 / 36.2 / FLUT / SV-A / D / 88.1 / 14.4 / 16.4
IPR / SV-A / D / 91.8 / 30.2 / 32.9 / FLUT / SV-A / D / 89.2 / 15.0 / 16.8
IPR / SV-B / A / 64.6 / 26.8 / 41.4 / FLUT / SV-B / A / 69.7 / 17.1 / 24.5
IPR / SV-B / A / 67.2 / 31.3 / 46.5 / FLUT / SV-B / A / 70.9 / 16.3 / 22.9
IPR / SV-B / A / 71.4 / 28.8 / 40.4 / FLUT / SV-B / A / 70.0 / 13.7 / 19.5
IPR / SV-B / B / 73.3 / 24.7 / 33.8 / FLUT / SV-B / B / 70.6 / 14.3 / 20.3
IPR / SV-B / B / 72.7 / 29.3 / 40.4 / FLUT / SV-B / B / 73.7 / 16.0 / 21.7
IPR / SV-B / B / 67.0 / 23.5 / 35.1 / FLUT / SV-B / B / 70.9 / 14.0 / 19.7
IPR / SV-B / C / 83.5 / 36.3 / 43.5 / FLUT / SV-B / C / 86.5 / 14.9 / 17.2
IPR / SV-B / C / 81.0 / 34.0 / 42.0 / FLUT / SV-B / C / 86.8 / 14.8 / 17.1
IPR / SV-B / C / 86.6 / 33.2 / 38.3 / FLUT / SV-B / C / 85.9 / 13.6 / 15.9
IPR / SV-B / D / 87.8 / 27.5 / 31.3 / FLUT / SV-B / D / 90.0 / 12.2 / 13.5
IPR / SV-B / D / 90.3 / 27.7 / 30.7 / FLUT / SV-B / D / 91.5 / 11.4 / 12.4
IPR / SV-B / D / 90.7 / 28.9 / 31.9 / FLUT / SV-B / D / 90.0 / 8.9 / 9.8
IPR / ML-A / A / 72.2 / 37.7 / 52.3 / FLUT / ML-A / A / 67.1 / 20.8 / 31.0
IPR / ML-A / A / 69.5 / 31.6 / 45.5 / FLUT / ML-A / A / 65.6 / 21.3 / 32.4
IPR / ML-A / A / 72.0 / 28.0 / 38.9 / FLUT / ML-A / A / 64.2 / 18.9 / 29.4
IPR / ML-A / B / 70.0 / 27.4 / 39.2 / FLUT / ML-A / B / 50.7 / 20.3 / 40.0
IPR / ML-A / B / 63.5 / 37.1 / 58.3 / FLUT / ML-A / B / 52.5 / 16.0 / 30.5
IPR / ML-A / B / 66.8 / 36.7 / 54.9 / FLUT / ML-A / B / 51.2 / 20.1 / 39.3
IPR / ML-A / C / 83.8 / 35.1 / 41.9 / FLUT / ML-A / C / 82.9 / 14.0 / 16.9
IPR / ML-A / C / 77.6 / 29.6 / 38.2 / FLUT / ML-A / C / 79.9 / 11.5 / 14.3
IPR / ML-A / C / 80.3 / 30.0 / 37.3 / FLUT / ML-A / C / 83.2 / 12.5 / 15.1
IPR / ML-A / D / 85.4 / 21.4 / 25.1 / FLUT / ML-A / D / 82.1 / 15.9 / 19.4
IPR / ML-A / D / 88.3 / 29.0 / 32.9 / FLUT / ML-A / D / 88.2 / 13.8 / 15.6
IPR / ML-A / D / 90.0 / 27.0 / 30.0 / FLUT / ML-A / D / 81.7 / 17.0 / 20.8
IPR / ML-B / A / 66.9 / 37.5 / 56.0 / FLUT / ML-B / A / 70.9 / 25.8 / 36.3
IPR / ML-B / A / 70.2 / 36.4 / 51.9 / FLUT / ML-B / A / 68.8 / 25.5 / 37.0
IPR / ML-B / A / 70.0 / 34.9 / 49.9 / FLUT / ML-B / A / 65.5 / 21.5 / 32.8
IPR / ML-B / B / 67.1 / 31.6 / 47.0 / FLUT / ML-B / B / 58.4 / 22.7 / 38.9
IPR / ML-B / B / 70.0 / 38.2 / 54.6 / FLUT / ML-B / B / 62.3 / 26.0 / 41.7
IPR / ML-B / B / 63.7 / 38.6 / 60.6 / FLUT / ML-B / B / 60.2 / 25.2 / 41.9
IPR / ML-B / C / 84.6 / 26.8 / 31.7 / FLUT / ML-B / C / 78.7 / 20.1 / 25.5
IPR / ML-B / C / 84.1 / 27.2 / 32.3 / FLUT / ML-B / C / 79.3 / 19.8 / 24.9
IPR / ML-B / C / 79.0 / 28.9 / 36.5 / FLUT / ML-B / C / 84.7 / 27.1 / 32.0
IPR / ML-B / D / 88.5 / 21.1 / 23.8 / FLUT / ML-B / D / 88.2 / 21.5 / 24.3
IPR / ML-B / D / 82.2 / 23.2 / 28.2 / FLUT / ML-B / D / 87.5 / 22.1 / 25.3
IPR / ML-B / D / 83.5 / 23.4 / 28.0 / FLUT / ML-B / D / 82.9 / 22.3 / 27.0
APPENDIX-A Con’d:TSLI Data using SET-A to D (2%w/w drug conc., 60L/min, 10 s)
Drug / Carrier / SET / ED (%) / FPFTD (%) / FPFED (%) / Drug / Carrier / SET / ED (%) / FPFTD (%) / FPFED (%)AS / Treh / A / 86.0 / 13.9 / 16.1 / IPR / Treh / A / 76.7 / 12.3 / 16.1
AS / Treh / A / 93.0 / 12.1 / 13.0 / IPR / Treh / A / 80.5 / 16.5 / 20.5
AS / Treh / A / 91.7 / 12.5 / 13.6 / IPR / Treh / A / 81.0 / 16.3 / 20.2
AS / Treh / B / 94.5 / 9.0 / 9.6 / IPR / Treh / B / 80.8 / 16.3 / 20.1
AS / Treh / B / 94.2 / 8.4 / 8.9 / IPR / Treh / B / 84.3 / 15.5 / 18.4
AS / Treh / B / 92.4 / 11.2 / 12.1 / IPR / Treh / B / 83.8 / 14.7 / 17.6
AS / Treh / C / 95.4 / 7.4 / 7.8 / IPR / Treh / C / 88.0 / 9.8 / 11.1
AS / Treh / C / 95.1 / 6.4 / 6.7 / IPR / Treh / C / 92.0 / 12.1 / 13.1
AS / Treh / C / 95.8 / 9.4 / 9.8 / IPR / Treh / C / 91.6 / 10.3 / 11.3
AS / Treh / D / 95.3 / 6.3 / 6.6 / IPR / Treh / D / 90.8 / 4.2 / 4.6
AS / Treh / D / 89.9 / 4.1 / 4.5 / IPR / Treh / D / 93.3 / 5.0 / 5.4
AS / Treh / D / 94.0 / 5.7 / 6.1 / IPR / Treh / D / 93.7 / 6.4 / 6.9
AS / Mann / A / 88.0 / 12.2 / 13.8 / IPR / Mann / A / 75.0 / 8.3 / 11.1
AS / Mann / A / 94.1 / 10.2 / 10.8 / IPR / Mann / A / 78.4 / 9.5 / 12.1
AS / Mann / A / 89.9 / 9.9 / 11.0 / IPR / Mann / A / 72.9 / 9.5 / 13.0
AS / Mann / B / 93.9 / 9.3 / 10.0 / IPR / Mann / B / 77.7 / 12.6 / 16.2
AS / Mann / B / 94.3 / 6.6 / 7.0 / IPR / Mann / B / 74.3 / 11.4 / 15.3
AS / Mann / B / 91.2 / 7.4 / 8.1 / IPR / Mann / B / 79.0 / 10.2 / 12.9
AS / Mann / C / 94.8 / 8.8 / 9.3 / IPR / Mann / C / 92.3 / 10.0 / 10.3
AS / Mann / C / 95.7 / 5.7 / 6.0 / IPR / Mann / C / 90.4 / 8.7 / 9.7
AS / Mann / C / 94.0 / 8.0 / 8.5 / IPR / Mann / C / 86.7 / 5.3 / 6.1
AS / Mann / D / 90.1 / 5.0 / 5.6 / IPR / Mann / D / 84.8 / 3.2 / 3.8
AS / Mann / D / 97.3 / 5.2 / 5.4 / IPR / Mann / D / 74.6 / 1.8 / 2.4
AS / Mann / D / 93.0 / 5.2 / 5.6 / IPR / Mann / D / 72.9 / 3.7 / 5.1
DSCG / Treh / A / 86.9 / 22.1 / 25.4 / FLUT / Treh / A / 64.9 / 7.9 / 12.1
DSCG / Treh / A / 85.6 / 15.3 / 17.9 / FLUT / Treh / A / 67.3 / 8.1 / 12.1
DSCG / Treh / A / 83.2 / 11.8 / 14.2 / FLUT / Treh / A / 65.7 / 11.0 / 16.7
DSCG / Treh / B / 88.4 / 17.4 / 19.7 / FLUT / Treh / B / 66.6 / 4.9 / 7.3
DSCG / Treh / B / 95.2 / 17.3 / 18.2 / FLUT / Treh / B / 64.7 / 5.4 / 8.3
DSCG / Treh / B / 86.4 / 17.5 / 20.3 / FLUT / Treh / B / 65.8 / 5.2 / 7.9
DSCG / Treh / C / 94.2 / 16.8 / 17.8 / FLUT / Treh / C / 87.6 / 8.3 / 9.4
DSCG / Treh / C / 94.4 / 16.6 / 17.6 / FLUT / Treh / C / 86.2 / 11.4 / 13.2
DSCG / Treh / C / 95.4 / 16.5 / 17.3 / FLUT / Treh / C / 86.9 / 8.8 / 10.2
DSCG / Treh / D / 95.4 / 11.2 / 11.7 / FLUT / Treh / D / 91.7 / 7.1 / 7.7
DSCG / Treh / D / 97.2 / 11.4 / 11.7 / FLUT / Treh / D / 88.4 / 6.5 / 7.4
DSCG / Treh / D / 93.9 / 10.4 / 11.1 / FLUT / Treh / D / 90.6 / 6.7 / 7.4
DSCG / Mann / A / 88.1 / 27.0 / 30.7 / FLUT / Mann / A / 67.5 / 11.8 / 17.5
DSCG / Mann / A / 86.8 / 20.4 / 23.5 / FLUT / Mann / A / 68.9 / 11.6 / 16.8
DSCG / Mann / A / 85.0 / 19.0 / 22.4 / FLUT / Mann / A / 71.8 / 14.6 / 20.3
DSCG / Mann / B / 90.0 / 17.1 / 19.0 / FLUT / Mann / B / 73.6 / 15.2 / 20.7
DSCG / Mann / B / 88.6 / 17.6 / 19.9 / FLUT / Mann / B / 77.4 / 13.9 / 17.9
DSCG / Mann / B / 86.3 / 15.4 / 17.8 / FLUT / Mann / B / 76.2 / 14.6 / 19.1
DSCG / Mann / C / 93.7 / 15.9 / 17.0 / FLUT / Mann / C / 90.5 / 13.9 / 15.4
DSCG / Mann / C / 92.5 / 18.2 / 19.7 / FLUT / Mann / C / 84.4 / 14.7 / 17.4
DSCG / Mann / C / 89.8 / 14.0 / 15.5 / FLUT / Mann / C / 86.9 / 14.4 / 16.5
DSCG / Mann / D / 94.7 / 12.9 / 13.6 / FLUT / Mann / D / 89.7 / 9.7 / 10.8
DSCG / Mann / D / 90.0 / 7.4 / 8.2 / FLUT / Mann / D / 91.6 / 9.8 / 10.7
DSCG / Mann / D / 86.5 / 9.4 / 10.9 / FLUT / Mann / D / 90.6 / 10.2 / 11.2
AS: Albuterol sulfate; DSCG: Disodium cromoglycate; IPB: Ipratropium bromide monohydrate; FLUT: Fluticasone propionate; SV-A and SV-B: sieved lactose monohydrate batches; ML-A and ML-B: milled lactose monohydrate batches; Treh: Trehalose dihydrate; Mann: Mannitol; SET: standardized entrainment tubes; ED: emitted dose; FPFTD: fine particle fraction from the total dose; FPFED: fine particle fraction from the emitted dose; TSLI: twin-stage liquid impinger.
APPENDIX-B: TSLI Data using additional SET-A1 to C1 (2%w/w drug conc., 60L/min, 10 s)
Drug / Carrier / SET / ED (%) / FPFTD (%) / FPFED (%)DSCG / ML-B / A1 / 75.9 / 40.2 / 52.9
DSCG / ML-B / A1 / 75.4 / 43.9 / 58.2
DSCG / ML-B / A1 / 74.0 / 37.3 / 50.4
DSCG / ML-B / B1 / 65.5 / 31.3 / 47.8
DSCG / ML-B / B1 / 64.3 / 30.1 / 46.7
DSCG / ML-B / B1 / 62.7 / 30.7 / 48.9
DSCG / ML-B / C1 / 80.9 / 29.1 / 36.0
DSCG / ML-B / C1 / 78.4 / 26.4 / 33.7
DSCG / ML-B / C1 / 80.7 / 27.9 / 34.6
AS / Mann / A1 / 91.3 / 8.7 / 9.5
AS / Mann / A1 / 91.9 / 13.6 / 14.8
AS / Mann / A1 / 92.7 / 9.1 / 9.8
AS / Mann / B1 / 92.2 / 6.8 / 7.3
AS / Mann / B1 / 92.9 / 5.7 / 6.2
AS / Mann / B1 / 90.4 / 5.8 / 6.4
AS / Mann / C1 / 94.0 / 5.5 / 5.8
AS / Mann / C1 / 95.3 / 8.7 / 9.1
AS / Mann / C1 / 93.7 / 4.9 / 5.2
1