Formulation Optimization of Controlled-Release Pellets of Metoclopramide Hydrochloride Using Dissolution Fit Factor Approach

Abstract

The purpose of this study was to optimize the formulation variables for the preparation of ethyl cellulose-coated nonpareils loaded with metoclopramide hydrochloride (MCL). The approach to evaluate the effectiveness of formulation parameters was monitored by release rate testing using dissolution fit factors as a tool. The content of ethyl cellulose used in the formulation was based on the drug-loaded weight. The interrelationship of each developed formulation and the reference formulation Gastro-Timelets® and their respective dissolution curves were evaluated using Moore's equation: f₂ = 50 × log {[1 + 1/n ∑ⁿ_{t = 1} Wt(Rt − Tt)²]⁻⁰⁵ × 100}. The relationship between the ethyl cellulose content in the formulation and the dissolution fit factor f₂ can be described as the following regression equation: Y = −0.054X² + 3.347X − 1.915 (r² = 0.99). The optimum ethyl cellulose content obtained from the equation was 30.8%. The type and content of plasticizer used in the formulation to achieve the greatest f₂ were determined to be Myvacet 9–40 at the concentration of 25%. Results indicated that using the release rate testing approach with the dissolution fit factor as a tool could provide valuable information for formulation optimization.