Benchtop-magnetic resonance imaging (BT-MRI) characterization of push-pull osmotic controlled release systems.
The mechanism of drug release from push-pull osmotic systems (PPOS) has been investigated by Magnetic Resonance Imaging (MRI) using a new benchtop apparatus. The signal intensity profiles of both PPOS layers were monitored non-invasively over time to characterize the hydration and swelling kinetics. The drug release performance was well-correlated to the hydration kinetics. The results show that (i) hydration and swelling critically depend on the tablet core composition, (ii) high osmotic pressure developed by the push layer may lead to bypassing the drug layer and incomplete drug release and (iii) the hydration of both the drug and the push layers needs to be properly balanced to efficiently deliver the drug. MRI is therefore a powerful tool to get insights on the drug delivery mechanism of push-pull osmotic systems, which enable a more efficient optimization of such formulations.
Novartis Pharma AG, Technical R&D, Fabrikstrasse 2, CH-4056 Basel, Switzerland.
Vincent
V
Malaterre
Hendrik
H
Metz
Joerg
J
Ogorka
Robert
R
Gurny
Nicoletta
N
Loggia
Karsten
K
Mäder
D002121:Calcium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry; D007203:Indigo Carmine / Q000737:chemistry; D017275:Isradipine / Q000737:chemistry / Q000493:pharmacokinetics; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D009997:Osmotic Pressure; D011092:Polyethylene Glycols / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets / Q000737:chemistry* / Q000493:pharmacokinetics; D014867:Water / Q000737:chemistry
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D005079:Excipients; D013229:Stearic Acids; D013607:Tablets; D014867:Water; C005062:acetylcellulose; D011092:Polyethylene Glycols; D012965:Sodium Chloride; C031183:stearic acid; D002482:Cellulose; D007203:Indigo Carmine; D017275:Isradipine