Development, characterization and evaluation of a pulsed -release tablet dosage form for low dose water soluble drugs

Various types of controlled release dosage forms such as wax matrix hydrophilic polymer matrix, osmotic pump and acrylic resin polymer encapsulated slow release for water soluble drugs have been developed and reported. However, there was no significant information available in the literature about the development and scale-up of pulse-release tablet dosage form for low dose water soluble drugs. This investigation was undertaken to develop, characterize and evaluate a new pulsed-release dosage form for a low dose water soluble drug with consistent drug release that combines polymer matrix and aqueous coating technology. The effect of scale-up on granulation, compression and coating of pulse-release tablet formulation containing low dose active drug made with hydroxypropyl methylcellulose (HPMC) as base excipients were investigated for two different formulation. The controlled release matrix tablets produced were seal coated using aqueous polymer latex dispersion to retard the drug release from the tablet cores for a period of 3–4 hours. Immediate release coat was developed to apply the initial dose of the drug onto the seal coated tablets. A factorial design was used to study the critical processing parameters that were known to influence coating process. The results of analysis of variance were used to predict the effect of various processing parameters on the response. Pair-wise comparisons of the dissolution results for two different scales and formulations using F2 metrics established by FDA SUPAC guidelines were used to evaluate similarity between drug release characteristics. Results indicate that adjustment of the blending time and headspace to blender capacity based on the size of the blenders used at various stages of scale-up is necessary to maintain constant blending geometry and equivalent mixing to produce uniform distribution of the active drug. Results also show that coating suspension spray rate and coating pan rotation speed significantly affect the coating uniformity. The content uniformity between tablets is significantly improved by using a low spray rate, low drug concentration in the coating solution and slower pan speed. Stability test results indicate that the developed formulation was stable when stored at ambient and accelerated storage conditions