Pulse release of doxazosin from hydroxyethylcellulose compression coated tablet: mechanistic and in vivo study

Chronotherapeutically programmed hydroxyethylcellulose (HEC) based compression coated doxazosin tablets were prepared and the influence of disintegrants croscarmellose sodium, L-hydroxypropylcellulose (L-HPC), gellan gum on drug release and in vivo performance were investigated. Infrared spectroscopy and differential scanning calorimetric studies did not indicate any excipient incompatibility in the tablets. The disintegrants induced a continuous water influx resulting in a rapid expansion of the membrane. The subsequent formation of fractures into the coats leads to a fast drug release after an initial lag time. Release rates indicated that croscarmellose sodium and L-HPC were directly proportional to their concentration in the formulations. In vitro optimized croscarmellose sodium-HEC matrix showed significantly faster (p < 0.05) drug release (t90% = 46 min) after an initial lag of 243 min. Disintegrant-HEC blended matrices were found significantly superior (p < 0.05) in terms of in vitro release and bioavailability in comparison to plain HEC matrices. Drug release kinetics followed modified power law and Weibull model (r > 0.99). The mechanism involved in release was anomalous transport and super case II transport with matrix swelling. The pulsatile tablets showed no changes either in physicochemical appearance, drug content or in dissolution pattern during its accelerated stability studies.