CHARACTERIZATION OF COMMERCIALLY AVAILABLE THEOPHYLLINE SUSTAINED-RELEASE OR CONTROLLED-RELEASE SYSTEMS - INVITRO DRUG RELEASE PROFILES

Release of theophylline, either in the form of free xanthine or complexed with choline or ethylene diamine, from commercially available dosage forms is modelled using a series of standard drug-release models. Those included the first order and the cube root models. Equations which take into account the geometries of the products were also assessed and compared with the more generic square root of time model. It is shown that in practice discrimination between the competing models is difficult even with use of mean square errors. All the products on the U.K. market showed pH-dependency although to variable extents. Sabidal(R), for example, gave good consistency within the pH range 2.1-6.9 but much slower release rates at pH 1.2. Such a profile may be desirable given the known irritant effects of the theophylline in the stomach. Lasma(R) showed a similar pH effect but the rates of release were extremely fast at pH 2.1 and above. This suggests a potential dose-dumping effect in vivo. Phyllocontin (R) showed relatively little pH variability in its release profiles. Ionic strength had a dramatic effect on drug release from Lasma(R) tablets. Sabidal(R) was also markedly affected as was Pro-Vent(R). These results certainly show that theophylline sustained-release products are not interchangeable without readjustment to steady-state blood levels.