Formulation Development and Optimization of Paliperidone Extended Release Tablet

Abstract

Schizophrenia (“split mind”) is deliberated as a prolonged psychological ailment often characterized by strange social behavior and failure to recognize what about reality. Patients suffering from schizophrenia utmost require chronic management with medications to control symptoms. Paliperidone is choice of atypical antipsychotic agent [Second-Generation Antipsychotics (SGAs)] for the treatment of Schizophrenia. Paliperidone is potent molecule associated with several side effects like anxiety, somnolence, dizziness, constipation, and extrapyramidal symptoms) occurred due to high blood plasma concentration of drug. Thus Objective of current investigation was to develop extended release(ER) cost-effective composition that control the blood plasma concentration of a drug and thereby prevent the adverse effects as well as to achieve dissolution profile same as the innovator formulation (Reference Listed Drug). Based on innovator characterisation, Quality Target Product Profile (QTPP) and initial risk assessment it was decided to develop a formulation using micronized API to enhance solubility and bioavailability. HPMC E50 Premium LV was selected as low viscosity grade to prevent initial burst release and HPMC E4M Premium CR was selected as high viscosity to extend the drug release up to 24 Hr. Butylated Hydroxy toluene (BHT) was included as antioxidant because Paliperidone undergoes oxidation degradation. 32 Factorial design was employed to optimize the polymer concentrations and to get desired formulation (Design) space. Check-point batches were conducted for validation of the design space and to check desirability obtain in mathematical optimization. Further modification in Enteric coating system was carried out to get initial release in gastric region by addition of water soluble pore former along with Eudragit L30 D55 polymer. Batches were evaluated for process variables, drug release profiles and kinetic modeling. Based on development and outcomes of experimental trials, Control strategy was designed for robust formulation. The results and control strategy demonstrated that performed experiments using QbD approach for Paliperidone can be used to formulate cost-effective conventional dosage form having similar dissolution profile as innovator.