Formulation Design and Optimization of Multi Unit Pellet Systems by Using Concept of Design of Experiment

Abstract

Metoprolol succinate is widely used in hypertension for effective control of blood pressure. Once a day sustained release tablet formulation available in market exhibits system failure and dose dumping which may due to monolithic system. This strongly suggests the need of formulation of Multi Unit Pellet Systems (MUPS). Hence the present investigation was aimed to systematically formulate and optimize MUPS of Metoprolol Succinate, by Extrusion – Spheronization Technique. Pellets were evaluated for Extrude properties, Sphericity, Micromeritic properties and Drug release. The preliminary batches were formulated using variety of diluents and polymers like Avicel PH101, Di- Calcium phosphate, Mannitol, HPMC K4M, HPMCK15M, Ethyl cellulose etc. as well as the amount and type of diluent, solvent system, binder, polymer etc. were also studied. The results of preliminary batches revealed that the amount of Avicel PH 101, HPMC K4M and Ethyl Cellulose plays critical role in Sphericity and drug release from pellets. These factors were systematically optimized using Design of Experiment (Using Simplex Lattice design). And the result revealed that Avicel PH 101 plays critical role for Sphericity, whereas HPMCK4M provided delayed drug release. The optimized batch was developed by validated model from the desired response region. The optimized batch was further evaluated for mechanical strength using texture analyzer and SEMresults were found satisfactory. The developed pellets were compressed to formulate tablet, however, the result suggested need of cushioning agents(s) and super-disintegrant for immediate release of intact pellets. Various combinations of Avicel PH 101 and PEG-4000 were explored as external cushioning agent and the Sodium Starch Glycolate was used as super-disintegrant. The optimized formulation was compared with marketed formulation and found satisfactory. Hence it was concluded that MUPS gives better controlled drug delivery as compared to monolithic systems.