Formulation Development and Evaluation of Duloxetine Hydrochloride Multi-Particulate Delayed-Release Capsules

Background: Multi-particulate drug delivery systems are mainly oral dosage forms consisting of a multiplicity of small discrete units, each exhibiting some desired characteristics. Duloxetine hydrochloride is acid-labile thus it is formulated as gastro-resistant pellets. Objective: The work aims to develop Delayed-release oral capsules comprising Duloxetine Hcl pellets which is similar in dissolution profile and bioavailability, there by establishing bio equivalence to that of the reference product-Cymbalta®. Methods: The pellets are formulated in a fluidised bed processor, by Wurster process. The finished pellet consists of four different layers, coated over the sugar spheres. The first layer is the drug layer, followed by a barrier layer to separate enteric layer and drug, finally a top layer that acts as a moisture barrier. The pharmaceutical equivalence and stability of finished product to that of the standard was the primary objective during the development of each layer. Thus, in all stages of development, the dissolution and stability were closely monitored and the excipients were optimized based omit. Results: Poor process efficiency, multi-pellet formation and low dissolution of the drug layer are resolved by the addition of HPMC, talc and corn starch respectively. The moisture permeability across the barrier layer was arrested by Opadry® AMB white. 25-30%. 25% coating thickness with Eudragit L-30-D55 provides acid resistance and timely drug release. Finally, a 5% coating with Opadry® AMB again provides complete moisture protection. Conclusion: Developed pharmaceutically equivalent and stable dosage form of Duloxetine Hydrochloride