Abstract

Controlled release dosage forms are essential in certain dosage regimens where release rate of drug impacts the effectiveness for therapy. In the present study, modified release dosage form of Domperidone was developed in the form of pellets which were subsequently compressed into tablet to disintegrate and swallow by patients without changing the release profile. Sustained release pellet formulation of Domperidone were developed by extrusion-spheronization and layering technique using Celphere® 102 and Suglet® as core seed and Kollicoat® SR 30 D as rate controlling polymer. 23 full factorial design (two level and three parameters) were applied to assess the impact of the different variables on properties of resulting pellets prepared by extrusion-spheronization. Different types of tableting excipients were combined to get better compressibility of pellets, out of which the combination of Ceolus granules and Ludipess was found as good tableting excipient. Release profile was assessed by mathematical modeling and followed first order release kinetics. Sustained releasing Domperidone Multiple Unit Pellet System (MUPS) prepared using Celphere 102 was found to possess rapid disintegration property, hardness and unaltered release profile even after compression.

 

Conclusions

Sustained release pellets formulation of Domperidone developed by extrusion & spheronization and subsequently coated with Kollicoat SR 30 D were not able to withstand compression failing to maintain the sustained drug release. However, pellets prepared by drug layering on Celphere 102 and Suglet as core seed and subsequently coating using Kollicoat SR 30 D as rate controlling polymer showed drug release over the period of 12 hours. Celphere 102 pellets, being smaller in size showed a greater control on drug release. Different types of tableting excipients were combined to get better compressibility of pellets. Combination of Ceolus granules with Ludipress was found to be having great potential to function as tableting excipient for MUPS. Mathematical modelling of release profile of Domperidone showed that release occurs in a first order kinetic profile. Various factors like property of pellets to be compressed, coating type & level, type and composition of tableting excipient and ratio of drug loaded pellets to tableting excipients were identified and optimized. Sustained releasing Multiple Unit Pellet System (MUPS) of Domperidone shows great potential in terms of hardness, rapid disintegration property, unaltered release profile and in converting them to suitable tablet dosage form.

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