pH-Thermosensitive Oral Hydrogels Containing Phenobarbital for a Potiential Pediatric Use

The purpose of this study was to develop a pH-thermosensitive oral chitosan-based hydrogels, able to release phenobarbital in the small intestine of the newborn. Phenobarbital is an active drug used in neonatal treatment of epilepsy. pH-thermosensitive hydrogels will improve its bioavailability and therapeutic efficiency with less side effects. This study allowed us to understand the free energy variation at the interface between chitosan chains themselves and the surrounding available molecules with its interactions behavour. Indeed, inverted tube method was used to prepare hydrogels containing 2.45 and 2.55% of chitosan, eudragitE100 and phenobarbital at 37+/-1°C via sol-gel transition. The characterization of their morphology was done by using XL SIRION 200 FEG SEM. In addition, conductivity, refractive index and density’s values were determinated. The phenobarbital release mechanism from hydrogels at different pH values, simulating the gastrointestinal tract of the newborn was also studed. UV / visible spectrophotometer SHIMADZU from the UV-2400PC series was used to determine the phenobarbital released amount as a function of time. The results showed that sol-gel transition time decreases when the chitosan concentration increases. In addition, it showed that the hydrogels structure was heterogeneous and the phenobarbital released amount were more important at pH simulating the small intestine at 2.45% of chitosan, final solution’s pH6.85 and with the presence of eudragitE100. These results were confirmed by conductivity’s values. The sols and hydrogels had a comparable refractive index and density’s values. The Korsmeyer-Peppas model was used to fit the phenobarbital release profiles. In short, the hydrogels formulated lend themselves to a phenobarbital pulsatile release usable in the newborn. The phenobarbital release profiles fitting makes possible to predict the phenobarbital amounts, which will be released at the action sites according to the need.