Report No xxxx - Instytut Fizyki JÄ drowej PAN

MRI INVESTIGATIONS OF HYDROGEL FORMATION
AND DIMENSIONAL CHANGES OCCURRING
IN HBS – PRELIMINARY STUDIES
Przemysław Dorożyński 1 , Piotr Kulinowski 2 , Andrzej Jasiński 2 , Renata Jachowicz 1
1 Department of Pharmaceutical Technology and Biopharmaceutics , Pharmaceutical Faculty,
Jagiellonian University, ul. Medyczna 9, 30-688 Kraków, Poland; 2 M.R.I. Laboratory,
Institute of Nuclear Physics, ul. Radzikowskiego 152, Kraków, Poland
1. Introduction
Our aim was to set up a system for obtaining Magnetic Resonance Images
simultaneously with the drug release profiles from Hydrodynamically Balanced Systems
(HBS).
HBS are the most common flotation dosage form. They are essentially composed of a drug
mixed with gel forming hydrocolloids. In contact with gastric fluid HBS swells and forms
hydrogel. The soft hydrogel barrier maintains a relative integrity of shape and a bulk density
less than 1 g/cm 3 . The drug is slowly released in the stomach by diffusion through the
gelatinous barrier and slow erosion of hydrogel on the surface of the dosage form [1].
The MRI is non destructive, non invasive method – it does not require sample slicing.
Since swelling polymeric matrices are very easy to damage, Magnetic Resonance Imaging
(MRI) can be used to observe the processes of solvent penetration inside the dosage form,
hydrogel formation and erosion [2]. It can be done without any capsule manipulation –
capsule remains all the time inside the flow-through cell under the flow condition.
2. Materials and methods
For MRI studies MR research system with digital MARAN DRX console (Resonance
Instruments) and 4.7T/310mm horizontal bore magnet (Bruker) equipped with actively
shielded gradient set of 200mm ID (Magnex Scientific) was used. Special flow-through cell
for HBS systems investigations was designed. Images were obtained using modified fast spin
echo sequence under a flow condition at flow rate 23ml/min. Imaging parameters were as
follows: field of view – 3.5cm, number of slices – 7 (for saggital slices), 23 (for axial slices),
slice thickness – 1mm, echo time – 19ms. Time constant of processes in investigated HBS are
in the range of 5-6 hours. The images of HBS were taken every half an hour. Constant
temperature of solution (37°C) was maintained during the course of the whole experiment.
3. Results
As an example, comparative study of HPMC 100k (Metholose 90 SH 100 000cp) with
LDopa 3+1 in two different solutions is presented. Two HCl solutions simulating gastric fluid
in fed and fasted state were used. Dimensional changes of the HBS capsules were detected by
observation of changes in proton signal intensity.
The dry cores in the HBS were observed for 5 hours. During this time the swelling in
axial direction was clearly evident. The longitudinal dimension of the capsule immersed in
fasted state simulated gastric fluid increased from 2,6 cm to 3,6 cm. Simultaneously the water
content in the swollen barrier gradually increased. The weight of the system increased almost
5 times during the experiment. The penetration of the solvent into the system was rather slow.
The decrease of the dry core radial dimension was not significant. The hydrogel from the
surface of the system was partially removed. In opposition, the hydrogel barrier produced in
the fed state simulated gastric fluid remained not changed during 5 hours of experiment.
23