Development of a Single Core Osmotic Tablet Containing Thermodynamically Stable Solid Dispersion of Nisoldipine
Product Development and Research, Sun Pharmaceutical Industries Limited, Sector-18, Gurgaon-122 015, Department of Pharmaceutical Sciences and technology, Birla Institute of Technology, Mesra, Ranchi-835 215, India
Product Development and Research, Sun Pharmaceutical Industries Limited, Sector-18, Gurgaon-122 015, India, E-mail: [email protected]
The main aim of the research work was to investigate the type and level of the polymer for solubility enhancement of nisoldipine by solid dispersion approach, followed by study of the formulation factors affecting design of a single unit, solid dispersion containing osmotic controlled release tablet. Solid dispersions with copovidone and Soluplus® were manufactured by hot melt extrusion technique, which offered possibility of scale up and commercialization. Dynamic vapour sorption and differential scanning calorimetry were used to characterize solid dispersions. Based on the glass transition temperature and dynamic vapour sorption data, nisoldipine-Soluplus®, at 1:1 ratio was selected to make dissolution enhanced solid dispersion system. The formulation factors affecting the drug release from the osmotic tablets such as type of dispersant, level of osmogen, %plasticizer in film coat and %coating, were studied by full factorial design. The drug release was found to increase with the increase in sodium chloride concentration in the core and polyethylene glycol level in the coating. The coating weight gain was found to decrease the drug release. Scanning electron microscopy revealed that the drug release occurred through the drilled hole and not through the extended release coating membrane. An interesting observation was found with respect to the dispersant type in the core. The high viscosity dispersant (Polyox) was found to facilitate complete release from the tablets compared to highly soluble, low viscosity dispersant (lactose). A design space was generated indicating that 36% osmogen in the core, a %polyethylene glycol level of 10-15% and weight gain at 5-7% can provide for a single core osmotic dosage form releasing ~80% drug in 12 h. The drug release from the monolithic tablets followed the Korsenmeyer-Peppas kinetics.