title: Novel application of MRI technique combined with flow-through cell dissolution apparatus as supportive discriminatory test for evaluation of controlled release formulations.
abstract: Dissolution studies cannot distinguish phenomena occurring inside the dosage forms when studying formulation with similar dissolution profiles-such formulations can behave differently when considering their physical changes. The application of flow-through dissolution apparatus integrated with magnetic resonance imaging (MRI) system for discriminative evaluation of controlled release dosage forms with similar dissolution profiles was presented. Hydrodynamically balanced systems (HBS) containing L: -dopa and various grades hydroxypropyl methylcelluloses were prepared. The dissolution studies of L: -dopa were performed at high field (4.7 T) MR system with MR-compatible flow-through cell. MRI was done with 0.14 x 0.14 x 1-mm spatial resolution and temporal resolution of 10 min to record changes of HBS parameters during dissolution in 0.1 M HCl. Structural and geometrical changes were evaluated using the following parameters: total area of HBS cross-section, its Feret's diameter, perimeter and circularity, area of hydrogel layer, and "dry core" area. While the dissolution profiles of L: -dopa were similar, the image analysis revealed differences in the structural and geometrical changes of the HBS. The mechanism of drug release from polymeric matrices is a result of synergy of several different phenomena occurring during dissolution and may differ between formulations, yet giving similar dissolution profiles. A multivariate analysis was performed to create a model taking into account dissolution data, data from MRI, information about chemical structure, and polymer viscosity. It provided a single model for all the formulations which was confirmed to be competent. The presented method has merit as a potential Process Analytical Technology tool.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Pharmaceutical Faculty, Jagiellonian University, ul. Medyczna 9, 30-688, Kraków, Poland. mfdorozy@cyf-kr.edu.pl
authors.forename: Przemyslaw P
authors.initials: PP
authors.lastname: Dorozyński
authors.forename: Piotr
authors.initials: P
authors.lastname: Kulinowski
authors.forename: Aleksander
authors.initials: A
authors.lastname: Mendyk
authors.forename: Anna
authors.initials: A
authors.lastname: Młynarczyk
authors.forename: Renata
authors.initials: R
authors.lastname: Jachowicz
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D017022:Flow Injection Analysis / Q000379:methods*; D007980:Levodopa / Q000032:analysis / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D012996:Solutions; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods
chemical_list: D003692:Delayed-Action Preparations; D012996:Solutions; D007980:Levodopa