ABSTRACT
In this study, high surface area mesoporous silica foam with cellular pore morphology (MCF) was used for injectable delivery of paliperidone, an antipsychotic drug used in patients suffering from bipolar disorder. The aim was to enhance paliperidone solubility and simultaneously to prepare long active intractable microspheres. For this reason paliperidone was first loaded in MCF silica, and the whole system was further encapsulated into PLA and PLGA 75/25w/w copolymer in the form of microspheres. It was found that paliperidone, after its adsorption into MCF, was transformed in its amorphous state, thus leading to enhanced in vitro dissolution profile. Furthermore, incorporation of the drug-loaded MCF to polymeric microparticles (PLA and PLGA) prolonged the release time of paliperidone from 10 to 15days.
Subject(s)
Antipsychotic Agents/chemical synthesis , Microspheres , Paliperidone Palmitate/chemical synthesis , Polymers/chemical synthesis , Silicon Dioxide/chemical synthesis , Antipsychotic Agents/metabolism , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/metabolism , Drug Compounding/methods , Drug Liberation , Injections, Subcutaneous , Paliperidone Palmitate/metabolism , Poloxalene/chemical synthesis , Poloxalene/metabolism , Polymers/metabolism , Porosity , Silicon Dioxide/metabolism , X-Ray Diffraction/methodsABSTRACT
In this study, mesocellular silica foam (MCF) was used to encapsulate paliperidone, an antipsychotic drug used in patients suffering from bipolar disorder. MCF with the drug adsorbed was further encapsulated into poly(lactic acid) (PLA) and poly(lactide-co-glycolide) (PLGA) 75/25 w/w microspheres and these have been coated with thiolated chitosan. As found by TEM analysis, thiolated chitosan formed a thin layer on the polymeric microspheres' surface and was used in order to enhance their mucoadhesiveness. These microspheres aimed at the intranasal delivery of paliperidone. The DSC and XRD studies showed that paliperidone was encapsulated in amorphous form inside the MCF silica and for this reason its dissolution profile was enhanced compared to the neat drug. In coated microspheres, thiolated chitosan reduced the initial burst effect of the paliperidone dissolution profile and in all cases sustained release formulations have been prepared. The release mechanism was also theoretically studied and three kinetic models were proposed and successfully fitted for a dissolution profile of prepared formulations to be found.
