Inhalation Sciences Sweden Ab · NGM:ISAB
Inhalation Sciences Sweden Ab — Technical Presentation (May 2025)
22 slides from Inhalation Sciences Sweden Ab's technical presentation, May 28, 2025
Slide 1: DissolvIt – evaluation report and presentation of data from the FDA funded study
DissolvIt® – evaluation report and presentation of data from the FDA funded study on Inhalation Sciences in vitro module Maria Malmlöf, Per Gerde, Manoush Masarrat 2025-05-28
Slide 2: Introduction
Introduction • The DissolvIt® system is an in vitro test model/dissolution apparatus that is built to resemble relevant lung physiology for evaluation of the dissolution- and absorption of inhalable drugs. • Drug particles are evenly distributed over glass cover slips and dissolved into a mucus simu
Slide 3: Project aims
Project aims • The aims of the FDA funded project were to: • Aim 1: Evaluate the discriminatory ability of the DissolvIt system using different formulations with known differences or similarities. • Aim 2: Directly compare DissolvIt data to IPL data in rat ex vivo as well as to clinical data in vivo
Slide 4: Inhalation products tested in DissolvIt within this project
Inhalation products tested in DissolvIt within this project 16 test products 9 commercially 6 manufactured micronized available DPIs 1 commercial available dry powders (pure API) pMDI 4
Slide 5: Methods: Aerosolization and dose deposition, dissolution testing
Methods: Aerosolization and dose deposition (PreciseInhale®) dissolution testing (DissolvIt®) 6 manufactured micronized dry powders (pure API) 9 commercially available DPIs 1 commercial available pMDI Dissolution testing in DissolvIt Test product 5 Aerosolization and dose deposition onto glass cover
Slide 6: Aim 1: Evaluate the discriminatory ability of the DissolvIt system
Aim 1: Evaluate the discriminatory ability of the DissolvIt system using different formulations with known differences or similarities ISAB Test product Evaluations performed code IS194 Budesonide, DISCUS, 3.29 µm (X50) Data evaluation of APSD and dissolution of products where the API PSD and API ma
Slide 7: Aim 1: Budesonide – different sizes, differences expected to be seen
Aim 1: Budesonide – different sizes, differences expected to be seen Budesonide * * * * The smaller particles (IS195) are dissolved faster, that is demonstrated by identifying a * shorter Tmax, higher normalized Cmax ….. * DissolvIt detects differences *Statistically significant difference p<0.05, S
Slide 8: Aim 1: Budesonide – different sizes, differences expected to be seen
Aim 1: Budesonide – different sizes, differences expected to be seen Budesonide ….and higher values of the cumulative dissolution. * * * DissolvIt detects differences * * *** *Statistically significant difference p<0.05, Student’s t-test, two-sided, assuming similar variance ISAB Test product Normal
Slide 9: Aim 1: Evaluate the discriminatory ability of the DissolvIt system
Aim 1: Evaluate the discriminatory ability of the DissolvIt system using different formulations with known differences or similarities ISAB Test product Evaluations performed code IS194 Budesonide, DISCUS, 3.29 µm (X50) Data evaluation of APSD and dissolution of products where the API PSD and API ma
Slide 10: Aim 1: Budesonide – different manufacturing methods
Aim 1: Budesonide – different manufacturing methods ISAB Test product Manufacturing MMAD GSD code method (µm) IS195 Budesonide, 2.14 µm (X50) DISCUS 1.78 ± 0.18 2.14 ± 0.05 IS196 Budesonide, 1.54 µm (X50) UMAX 1.59 ± 0.12 1.98 ± 0.13 - DISCUS = Dispersive crystallization with ultrasound, gives more
Slide 11: Aim 1: Budesonide – different manufacturing methods, differences expected
Aim 1: Budesonide – different manufacturing methods, differences expected to be seen * Budesonide Budesonide * * * * * * * * * ** *Statistically significant difference p<0.05, Student’s t-test, two-sided, assuming similar variance Normalized Cumulative dissolution and absorption (%) after Test ISABf
Slide 12: Aim 1: Evaluate the discriminatory ability of the DissolvIt system
Aim 1: Evaluate the discriminatory ability of the DissolvIt system using different formulations with known differences or similarities ISAB Test product Evaluations performed code IS406 Symbicort Turbohaler 320/9 (Bud/For F), DPI APSD determination and dissolution testing in DissolvIt for both APIs
Slide 13: Brand name (Symbicort Turbohaler) and generic product (Bufomix Easyhaler)
Brand name (Symbicort Turbohaler) and generic product (Bufomix Easyhaler) – similarities expected to be seen# Symbicort Turbohaler is a brand name product in Europe, and Bufomix Easyhaler is now an approved generic product in Europe. Both contains two APIs, budesonide and formoterol. No statisticall
Slide 14: Aim 2: Directly compare DissolvIt data to IPL data and clinical data
Aim 2: Directly compare DissolvIt data to IPL data in rat ex vivo as well as to clinical data in vivo PreciseInhale DissolvIt – in vitro Clinical exposures – in vivo - Non-biological system physiologically Isolated and Perfused Lung (IPL) – ex vivo resembling the lung - Comprises an artificial air-b
Slide 15: Aim 2: Directly compare DissolvIt data to IPL data in rat ex vivo
Aim 2: Directly compare DissolvIt data to IPL data in rat ex vivo as well as to clinical data in vivo ISAB Test product Evaluations performed code IS406 Symbicort Turbohaler 320/9 (Bud/For F), DPI APSD determination and dissolution testing in DissolvIt for both APIs in a brand name product versus a
Slide 16: DissolvIt and IPL comparison – in vitro ex vivo correlation (IVEVC)
DissolvIt and IPL comparison – in vitro ex vivo correlation (IVEVC) - Similar dissolution/absorption curves for both FP and Sal as well as same order of magnitude for Cmax for both FP and Sal from Seretide Evohaler 250/25 in DissolvIt and IPL - Similar dissolved and absorbed % API from Seretide Evoh
Slide 17: IVIVC – in vitro/ex vivo in vivo correlation
IVIVC – in vitro/ex vivo in vivo correlation Sal FP - Circulatory clearance of Sal and FP from Seretide Evohaler 250/25 pMDI in DissolvIt (green), IPL (orange) and clinic* (blue). - DissolvIt data compares more directly to IPL data and describes dissolution and absorption of substance in the lung on
Slide 18: Aim 3: Investigate the potential for in vivo predictability of DissolvIt data
Aim 3: Investigate the potential for in vivo predictability of DissolvIt data by performing physiologically-based biopharmaceutical modelling - The FP dissolution data generated in DissolvIt for Seretide Evohaler 250/25 pMDI together with dose deposition data from literature were used for PBB modeli
Slide 19: Can DissolvIt predict clinical data?
Can DissolvIt predict clinical data? PBB modelling of FP in Seretide Evohaler 250/25 pMDI Log Linear axes axes FP FP PBB = physiologically-based biopharmaceutical, FP = fluticasone propionate, Cp = plasma concentration, Red dotted line (calculated) = DissolvIt dissolution data after PBB modeling, Bl
Slide 20: Conclusions
Conclusions • DissolvIt detects expected differences in dissolution/absorption originating from • Different particle sizes (budesonide) • Difference in API manufacturing method (UMAX and DISCUS manufacturing of budesonide) • DissolvIt detects similarities in dissolution/absorption as expected for •
Slide 21: Acknowledgement
Acknowledgement - FDA - pharm-analyt (LC-MS/MS analysis) - Karolinska Institutet (SEM images) - Emmace (development of Mimetikos Preludium module and PBB modeling) 21
Slide 22: Q/A
Q/A
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