Paliperidone ascending controlled-release pellets with osmotic core and driven by delayed osmotic pressure

The aim of this work was to develop an ascending controlled-release pellet (ACRP) of paliperidone to improve poor solubility and provide a stable blood drug concentration. The inner core was produced by mixing different ratios of sodium chloride as an osmotic substance and microcrystalline cellulose (MCC) to offer a pressure drive when in contact with medium. After, the drug layer was processed by a liquid-layering method, with paliperidone ground to a nano-size in order to improve the solubility and modify the final release profile. Finally, in combination with an isolation layer and coating film, initial burst release could be prevented and the migration of medium was impeded. The results showed that due to the sustained-release film, the release of ACRP was less than 10% in the initial 4 h, and then up to 60% as the sodium chloride dissolved and provided an increasing pressure difference over the next 8 h, with an ascending rate similar to that of osmotic pump tablets, Invega, in pH 1.2 hydrochloric acid solution. The release profile of ACRP was most suitable for the DoseResp curve, and so the mechanism was explained by delayed osmotic pressure caused by the osmotic substance and nano-crystal reservoir controlled-membrane system.