Formulation and Stabilization of Duloxetine Hydrochloride Delayed Release Pellets with the Aid Non Ionic Barrier Layer

Abstract

The main objective of the present study is to formulate a stable Duloxetine HCl delayed release pellets with the aid of non ionic protective layer between drug layer and enteric layer. Duloxetine HCl is highly unstable at acidic environment. The preformulation study reveals, Duloxetine HCl is incompatible with enteric polymers, due to the presence of free acid in the enteric polymer. Duloxetine HCl is also unstable at alkaline pH. Hence, a nonionic polymer is selected in barrier coating. Duloxetine hydrochloride enteric coated pellets were formulated using fluidized bed process with different levels of barrier coating. Three separate layers, the drug layer, the barrier layer and the enteric layer, were coated on to the inert core pellets, sugar spheres. The enteric coated pellets were top coated using film coating material and encapsulated in hard gelatin capsule shell. The probability of interaction of enteric polymer with duloxetine is very high during shelf life. The filled capsules were evaluated for description, Assay, Acid resistance and Drug release in pH 6.8 Phosphate buffer at initial and 6 months accelerated condition (40 ± 2°C/75± 5%RH), to conclude the % build up of barrier coating required to avoid the interaction between duloxetine hydrochloride and enteric polymer. The formulation with 10% & 15% barrier coating are failed to control the interaction between duloxetine hydrochloride and enteric polymer. The formulation with 20% barrier coating was found to be stable, and the interaction between duloxetine hydrochloride and enteric polymer was controlled.