PMID- 26091361
OWN - NLM
STAT- MEDLINE
DCOM- 20160513
LR  - 20191210
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 12
IP  - 8
DP  - 2015 Aug 3
TI  - Evaluation of the Transwell System for Characterization of Dissolution Behavior 
      of Inhalation Drugs: Effects of Membrane and Surfactant.
PG  - 2618-24
LID - 10.1021/acs.molpharmaceut.5b00221 [doi]
AB  - Assessing the dissolution behavior of orally inhaled drug products (OIDs) has 
      been proposed as an additional in vitro test for the characterization of 
      innovator and generic drug development. A number of suggested dissolution methods 
      (e.g., commercially available Transwell or Franz cell systems) have in common a 
      membrane which provides the separation between the donor compartment, containing 
      nondissolved drug particles, and an acceptor (sampling) compartment into which 
      dissolved drug will diffuse. The goal of this study was to identify and overcome 
      potential pitfalls associated with such dissolution systems using the inhaled 
      corticosteroids (ICS), viz., budesonide, ciclesonide, and fluticasone propionate, 
      as model compounds. A respirable fraction (generally stage 4 of a humidity, flow, 
      and temperature controlled Andersen Cascade Impactor (ACI) or a Next Generation 
      Impactor (NGI)) was collected for the tested MDIs. The dissolution behavior of 
      these fractions was assessed employing the original and an adapted Transwell 
      system using dissolution media which did or did not contain surfactant (0.5% 
      sodium dodecyl sulfate). The rate with which the ICS transferred from the donor 
      to the acceptor compartment was assessed by HPLC. Only a modified system that 
      incorporated faster equilibrating membranes instead of the original 0.4 mum 
      Transwell membrane resulted in dissolution and not diffusion being the 
      rate-limiting step for the transfer of drug from the donor to the acceptor 
      compartment. Experiments evaluating the nature of the dissolution media suggested 
      that the presence of a surfactant (e.g., 0.5% SDS) is essential to obtain rank 
      order of dissolution rates (e.g., for budesonide, fluticasone propionate, and 
      ciclesonide) that is in agreement with absorption rates of these ICS obtained in 
      studies of human pharmacokinetics. Using the optimized procedure, the in vitro 
      dissolution behavior of budesonide, ciclesonide, and fluticasone propionate 
      agreed approximately with descriptors of in vivo absorption. The optimized 
      procedure, using membranes with increased permeability and surfactant containing 
      dissolution medium, represents a good starting point to further evaluate in 
      vitro/in vivo correlations.
FAU - Rohrschneider, Marc
AU  - Rohrschneider M
FAU - Bhagwat, Sharvari
AU  - Bhagwat S
AD  -  section signCollege of Pharmacy, University of Florida, Gainesville, Florida 32610, United 
      States.
FAU - Krampe, Raphael
AU  - Krampe R
AD  -  section signCollege of Pharmacy, University of Florida, Gainesville, Florida 32610, United 
      States.
FAU - Michler, Victoria
AU  - Michler V
AD  -  section signCollege of Pharmacy, University of Florida, Gainesville, Florida 32610, United 
      States.
FAU - Breitkreutz, Jorg
AU  - Breitkreutz J
AD  -  parallelHeinrich Heine Universitat Dusseldorf, Universitatsstrasse 1, 40225 Dusseldorf, 
      Germany.
FAU - Hochhaus, Gunther
AU  - Hochhaus G
AD  -  section signCollege of Pharmacy, University of Florida, Gainesville, Florida 32610, United 
      States.
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20150709
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Drugs, Generic)
RN  - 0 (Oral Sprays)
RN  - 0 (Pregnenediones)
RN  - 0 (Surface-Active Agents)
RN  - 51333-22-3 (Budesonide)
RN  - CUT2W21N7U (Fluticasone)
RN  - S59502J185 (ciclesonide)
SB  - IM
MH  - Administration, Inhalation
MH  - Adrenal Cortex Hormones/administration & dosage/pharmacokinetics
MH  - Budesonide/administration & dosage/pharmacokinetics
MH  - Cells, Cultured
MH  - Drugs, Generic/*administration & dosage/*pharmacokinetics
MH  - Fluticasone/administration & dosage/pharmacokinetics
MH  - Humans
MH  - Membranes/drug effects/*physiology
MH  - *Oral Sprays
MH  - Pregnenediones/administration & dosage/pharmacokinetics
MH  - Respiratory Therapy/methods
MH  - Respiratory Tract Absorption/drug effects
MH  - Solubility
MH  - Surface-Active Agents/*pharmacology
MH  - Tissue Culture Techniques/*instrumentation/methods
OTO - NOTNLM
OT  - Transwell
OT  - dissolution medium
OT  - dissolution methods
OT  - inhalation
OT  - inhaled corticosteroids
EDAT- 2015/06/20 06:00
MHDA- 2016/05/14 06:00
CRDT- 2015/06/20 06:00
PHST- 2015/06/20 06:00 [entrez]
PHST- 2015/06/20 06:00 [pubmed]
PHST- 2016/05/14 06:00 [medline]
AID - 10.1021/acs.molpharmaceut.5b00221 [doi]
PST - ppublish
SO  - Mol Pharm. 2015 Aug 3;12(8):2618-24. doi: 10.1021/acs.molpharmaceut.5b00221. Epub 
      2015 Jul 9.