Development and evaluation of an optimised theophylline timed release tablets for chronotherapeutic drug delivery in nocturnal asthma

Abstract

Background: Chronopharmaceutics is a branch of pharmaceutics devoted to the design and evaluation of drug delivery systems that releases a bioactive agent at a rhythm that ideally matches the biological requirement of a given disease.
Aim: To develop and evaluate an optimized compression coated timed release tablet (CCTRT) containing theophylline, a bronchial dilator in the inner core as a chronotherapeutic drug delivery system.
Methods: The CCTRT containing theophylline in the inner core tablets (CT) were prepared using an admixture of granulated lactose, microcrystalline cellulose (MCC) and Brachystegia eurycoma (BE) powder in different ratios in order to achieve a predetermined lag time for chronotherapy. The CCTRT were compressed at 35 units in the arbitrary load scale on the tableting machine. The parameters determined were tablet hardness, friability, drug content, disintegration test and in vitro dissolution studies.
Results: The mean tablet hardness value for the CT and CCTRT were 4.1±0.3kg/cm3 and between 9-13.5kg/cm3 respectively. The mean friability values for the CT and all CCTRT formulations were < 0.33%, while the drug content uniformity of the tablets was ≥ 99%. The disintegration time for the CT was < 4 min. The release profile showed that all the CCTRT exhibited a distinct lag time before burst release of theophylline. Lag time was dependent on the ratio of granulated lactose/MCC/BE in the outer shell. The lag time for all the formulations was from 0 to 4h, and it decreased with increase in the amount of MCC in the outer layer.
Conclusion: Formulation CCTRT5 was considered optimized formulations since it yielded a predetermined lag time of 4 h before burst release of theophylline from the CCTRT. The indication is that this design can be utilized to achieve chronotherapeutic drug delivery systems of theophylline for the management of chronic illnesses such as asthma.

Keywords: Theophylline, Time release tablets, Brachystegia eurycoma, Lag time, Chronotherapeutic delivery systems