Chronomodulated rupturable pulsatile drug delivery of theophylline: preparation and in vitro characterization

The aim of the present study was to develop and evaluate chronomodulated rupturable pulsatile
drug delivery of theophylline for the treatment of nocturnal asthma. Core tablets containing theophylline
were coated with two consecutive layers, an inner swelling layer and an outer rupturable coating
layer. The effect of formulation variables such as molecular weight of outer rupturable coating layer, type
and amount of swelling layer, weight gain of coating film and influence of paddle speed on drug release
were investigated. The drug release from the pulsatile tablets exhibited an initial lag period, followed by a
stage of rapid drug release. The optimal level of swelling layer (crospovidone) to achieve a fast and complete
release was 20 % w/w. The results indicated that lag time was prolonged with the increased weight
gain of coating film. Also no significant difference in the drug release was observed for different rotational
speeds. In accordance with the chronomodulated therapy of asthma, the lag time criterion of 5 hours was
satisfied by formulation having 11 % weight gain of outer rupturable layer.
Colegio de Farmacéuticos de la Provincia de Buenos Aires