Mechanistic Tools to Understand Factors Controlling In Vitro Drug Release

In addition to the various novel apparatus described above, there are also novel tools available to improve the characterization of the dosage form behavior during the in vitro test, so that more information is gained than simply a drug release profile. These tools therefore improve the mechanistic understanding of the factors controlling the drug release profile. They include the use of novel techniques to measure the size of disintegrated particles in situ in a dissolution vessel [29], and the use of magnetic resonance imaging (MRI) to better characterize the mechanism of drug release [30, 31].

The MRI imaging technique is now possible with both high-field equipment for high-quality image analysis [32], and low-field equipment that may be located in a standard laboratory [33]. The use of a flow through cell, identical in design to that specified in the main pharmacopeias, is advantageous as the dosage form can be held in position, and the width of the dissolution cell means the magnet and dosage form can be in close proximity in a small fluid volume [34]. MRI imaging is of particular value for modified release formulations, as gaining an understanding of the changes occurring within the dosage form itself during the in vitro drug release test can improve the formulation design process, and identify underlying mechanisms contributing to drug release. A set of sample images for an osmotic pump modified release formulation is shown in Fig. 5.5. Changes in the hydration within the two compartments within the formulation can be detected, as can the plume of material that is forced out of the drilled orifice in the outer coat. Quantitative analysis of the hydration rate and erosion rate of modified release formulations are also possible via the use of image analysis software.

Fourier Transform Infra Red (FTIR) spectroscopy has also been reported as of value in the mechanistic understanding of dissolution. This technique has the advantage of providing a degree of spatial understanding as to where different components such as the drug and polymer are located during the dissolution process [35].

Fig. 5.5 A series of images (over about 12 h) for a nifedipine osmotic pump formulation taken with a Bench-top MRI. The hydration of the bilayer and the extrusion of the hydrated material out of the single orifice can be visualized

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