Ana-Maria Oprea

In vitro and in vivo theophylline release from cellulose/chondroitin sulfate hydrogels

In vitro and in vivo release of the theophylline, loaded in mixed polysaccharidic cellulose/chondroitin sulfate (C/CS) hydrogels has been evaluated. The C/CS hydrogels in various mixing ratios obtained by a crosslinking technique were supplementary characterized by swelling studies in a pH 2.2 acidic solution at 37 °C, simulating the gastrointestinal medium, as in vivo theophylline delivery was done by oral administration. The hydrogels loading degree with theophylline was evaluated by near infrared chemical imaging (NIR-CI) technique and confirmed also by FT-IR spectroscopy. Based on PLS-DA (partial least squares-discriminate analysis) prediction, the drug loading was found up to 92.5%. The in vitro release profiles of theophylline from C/CS hydrogels showed that an increase of chondroitin sulfate leads to a decreased theophylline percent released, increased half release time and time to reach maximum percent released. During in vivo test, the raw theophylline was rapidly, absorbed, distributed, and eliminated. Comparatively with raw drug administration, the t1/2 and AUC0-72 value were 4 times higher for theophylline loaded into 50/50 C/CS hydrogel. A good in vitro-in vivo correlation was found. A retarded release, controlled by CS content can be achieved by using mixed hydrogels as carriers.

Evaluation of crosslinked chitosan hydrogels as carriers for prolonged delivery of some novel nitric oxide donor compounds based on theophylline and paracetamol

Abstract The hydrogels of crosslinked chitosan with different glutaraldehyde amounts have been “in vitro” tested as carriers for prolonged release of some drugs for inflammatory and bronchopulomonary diseases. These hydrogels have been loaded with two novel nitric oxide donors, derivatives of 7-[2-nitroxyacethyloxy- 3-(4-acethyl-amino-phenoxy)-propyl]-8-R-1,3-dimethyl-xanthine compounds (R=H, NO2 for 65 and respectively 77 compounds) designed as multitarget drugs and parent compounds as paracetamol, theophylline, two xanthine derivatives 7-[2- hydroxy-3-(4-acethyl-amino-phenoxy)-propyl]-8-R-1,3-dimethyl-xanthine derivatives with (R=H, NO2 for D1 and respectively D2) and their release was evaluated in an acidic solution (pH=2.2) simulating the gastric fluid. Results have been correlated with the swelling behaviour which was also followed in acidic media with pH=2.2. The relationships between the release profiles and kinetics and matrix characteristics and/or drug properties have been established.