Dissolution Testing Methods for Poorly Soluble Compounds - continued
Posted by Dr. Theo Kapanadze, D.Sc., Ph.D on Mon, Jun 21, 2010 @ 09:47 AM
As I pondered my last blog entry, I felt that I needed to expand on the topic of dissolution methods for poorly soluble compounds for sustained or extended release formulas.
Time release technology, also known as sustained-release, extended-release, controlled-release, modified release or continuous-release is a mechanism used in tablets or capsules to dissolve slowly and release a drug over time. The advantages of sustained-release tablets or capsules are that they can often be taken less frequently than instant-release formulations of the same drug and that they keep steadier levels of the drug in the blood stream.
They involve complicated excipients and preparation technologies. Sustained release formulations often need two kinds of dissolution media to simulate the human gastrointestinal pH-acid stage and buffer stage. Some drugs are enclosed in polymer-based tablets with a laser-drilled hole on one side and a porous membrane on the other side. Stomach acids push through the porous membrane, thereby pushing the drug out through the laser-drilled hole. In time, the entire drug dose releases into the system while the polymer container remains intact, to be later excreted through normal digestion.
In some sustained release formulations, the drug dissolves into the matrix and the matrix physically swells to form a gel, allowing the drug to exit through the gel's outer surface. The difference between controlled-release and sustained-release is that controlled-release is a perfectly zero-order release; that is, the drug releases over time irrespective of concentration. Sustained-release implies slow release of the drug over a time period and it may or may not be a controlled-release. Traditionally, a drug dissolution release test for these formulations could require a day to complete sample analyses, making dissolution testing a time-consuming and labor-intensive procedure.
Over the last ten years, traditional methods of drug dissolution testing have been gradually replaced by fiber-optic dissolution systems in which a fiber-optic probe is inserted directly into each vessel to perform measurements in situ. Real-time drug dissolution release is determined in the vessels without sample removal, greatly simplifying the testing procedure.
The in situ fiber-optic dissolution system has proved to be productive, useful, labor saving and can acquire more information than conventional dissolution testing methods. The rapid in situ data collection capability of the system makes it possible to characterize a real-time dissolution profile. The fiber-optic dissolution system is widely applying for formulation development, bioequivalence research, and product release or stability studies.