In vitro release of theophylline from cross-linked gelatin capsules

Hard gelatin capsules were manufactured in our laboratory and cross-linked with terephtaloyle chloride before being filled with pure theophylline powder. Different reaction times were used to carry out the cross-linking process, either before or after drying of capsules. The in vitro drug release was carried out on comparison with commercial and laboratory-made conventional hard gelatin capsules and with Dilatrane(R). Release profiles showed that cross-linking before or after drying of capsules allowed sustained release of drug. However, a slower rate of release was shown from capsules cross-linked before drying. The rate of release decreased when the cross-linking reaction time was increased. When the reaction time was of 30 min, capsules exhibited a nearly zero-order release (r = 0.999) with a cumulative drug release of 63.24 +/- 10.48% only. Cumulative drug release, DT50% and DE from capsules cross-linked before drying had nearly the same release characteristics as Dilatrane(R). Cross-linking before and after drying of capsules permitted showing up the influence of moisture on the cross-linking density and, therefore, on the rate of drug release. Copyright (C) 1996 Elsevier Science B.V.