Biodegradable cross-linked prodrug of the bronchial dilator Vephylline. 2. Kinetics and quantum chemical studies on the release mechanism.

Experimental thermodynamics studies and quantum chemical reaction path calculations on the hydrolytic degradation of Poly-vephyllinemalate microspheres in acidic and basic media were performed. It was possible to make a conclusion on the release mechanism of free Vephylline as follows: a hydrolytic cleavage of the ester bonds between molecular fragments of R,S-malic acid takes place and leads to a soluble oligoester fraction. Then, further hydrolysis of the ester bonds between the xanthine fragment and R, S-malic acid leads to the release of Vephylline as free base. The hydrolytic process takes place in acidic solution with rapid degradation of the ester bonds between the malic acid monomers and by far slower degradation of the ester bonds between the malic acid and Vephylline. In basic solution both steps of the hydrolysis are fast processes leading to a complete release of free Vephylline within 1 h. The process of Vephylline release is under entropic control. The experimental results are well correlated to the results obtained after kinetics investigation and after AM1 quantum chemically calculated energy barriers in the reaction path leading to the tetrahedral intermediates of the hydrolytic reactions. This conclusion is in good accordance with an indirect study on the release mechanism of Vephylline from its polymeric prodrug, paying attention to the biological response, reported previously.

[Characterization of drug absorption from the gastrointestinal tract with the use of numeric deconvolution]. / Charakterisierung der Arzneistoffabsorption aus dem Gastrointestinaltrakt mit Hilfe der numerischen Dekonvolution.

The present investigation is concerned with the absorption of drugs from the gastrointestinal tract. The duration of absorption of drugs was calculated using numerical deconvolution. Clinical data were obtained from the literature. The absorption of 36 different drugs is characterized. The results show that the duration of absorption is not uniform. Penicillins and tetracyclines are absorbed for about 3 hours after application. Most drugs are absorbed during 4 to 6 hours. A few drugs, e.g. theophylline or metoprolol, are absorbed for more than 12 hours from the gastrointestinal tract.