Development and optimisation of novel oral formulation of an opioid analgesic using central composite design

Abstract

Introduction of matrix type sustained release systems were a breakthrough for novel oral drug delivery systems. Present research focuses on the development and evaluation of Fentanyl citrate sustained release formulations. It is a potent, sparingly soluble synthetic opioid analgesic with rapid onset and short duration of action. Considering the half-life of the drug which is 1.5 h, there is a strong clinical need and market potential for delivery systems that will deliver drug in controlled and prolonged manner. A number of strategies were planned for formulation development and evaluation such that they demonstrate robust stability and in vitro-in vivo performance using putative hydrophilic polymer HPMC (HPMCK 15M) in combination with hydrophobic polymer Ethyl cellulose N10. A Central composite design was employed to get an optimum formulation suitable for once a day administration. Effects of formulation variables, hydrodynamic conditions and agitational variations on drug release profile were also investigated. Drug release mechanisms using various mathematical kinetic models are discussed. The developed matrix tablets were successfully prepared without the need for functional coating thus promising to be a cost effective formulation with high commercial probability.

Keywords

• matrix system
• opioid
• analgesic
• sustained release
• oral delivery
• factorial design
• central composite