Studies in Oxcarbanepine Modified Release Formulations Using Quality by Design Approach

Abstract

Oxcarbazepine, an antiepileptic drug, is used in the treatment of partial and generalized tonic-clonic seizures in children and adults. The maximum dose administered per day is 2400 mg and administered 2 to 3 times in divided doses. It is available in market as 150, 300 and 600 mg of immediate release (IR) and extended release (ER) tablets. Immediate release of high dose of oxcarbazepine leads to side effect such as dizziness, drowsiness, fatigue, nausea, vomiting, headache, sleeping trouble, acne, dry mouth or constipation which anticipate the modification of oxcarbazepine release from the formulation for better therapeutic efficacy and patient compliance. The available extended release formulation is tablet, unit solid dosage form. The objective of the presented investigation was to develop twice a day oral modified release multiparticulate drug delivery system of oxcarbazepine to overcome disadvantages associated with unit modified release solid dosage form. newlineRequired release profile was generated using pharmacokinetic parameters of oxcarbazepine and was used for comparison of developed formulations. Three different dosage forms, microspheres, pellets and modified release granules were prepared adopting systematic approaches i.e. Quality by Design (QbD). newlineMicrospheres were prepared by multiple emulsion solvent evaporation technique using chitosan and ethyl cellulose as release retarding polymers. Quality targeted product profile (QTPP) and critical quality attributes (CQAs) were identified. Critical material attributes (CMAs) and critical process parameters (CPPs) were identified by risk assessment. The selected factors were screened by employing Plackett and Burman screening design. The most critical factors (temperature and volume of water) were used for further optimization (32 full factorial design). All the batches showed small particle size and good % encapsulation efficiency. Different approaches were tried to decrease initial burst release. newlinePellets were prepared by extrusion spheronization techn