DESIGN AND CHARACTERIZATION OF CHRONOPHARMACEUTICAL DRUG DELIVERY OF THEOPHYLLINE

Chronopharmacokinetic  studies have been reported for many drugs in an attempt to explain chronopharmacological phenomena and demonstrate that the time of administration is a possible factor of variation in the pharmacokinetics of a drug. The present study aimed at preparing a novel time dependent pulsed release system containing ‘pellets in-capsule’ device plugged by biodegradable polymers for the programmed release of theophylline for the treatment of nocturnal asthma. The pellets of theophylline were prepared using direct compression method containing a superdisintegrant. Physical characterization of the plug and pellets used was under taken using a range of experimental technique. Karaya gum, Xanthum gum and cross-povidone XL 10 were used as polymers for making plug which were fitted on to the capsule. Factors studied in design were percentage of drug entrapment, swelling index and the effect of plug position on In-vitro drug release. Dissolution studies of pulsatile capsule device in media with different pH (1.2, 6.8 and 7.4) showed that drug release in colon could be modulated by optimizing the concentration of polymers in the plug and also the position of plug. The study showed that, lag time prior to drug release was highly affected by the plug position. The dissolution data revealed that the plug position and the ratio of polymers are very important to achieve a optimum formulation. Different hydrogel polymers were used as plugs, to maintain a suitable lag period and it was found that the drug release was controlled by the proportion of polymers used. The FTIR, DSC studies pointed out there was no such incompatibility between drug and excipients. Stability study of the optimized formulation indicates no significant difference in release profile after a period of one month.