Formulation optimization of controlled-release pellets of metoclopramide hydrochloride using dissolution fit factor approach

The purpose of this study was to optimize the formulation variables for the preparation of ethyl cellulose-coated nonpareils loaded with metoclopramid e hydrochloride (MCL). The approach to evaluate the effectiveness of formul ation parameters was monitored by release rate resting using dissolution fi t factors as a tool. The content of ethyl cellulose used in the formulation was based on the drug-loaded weight. The interrelationship of each develop ed formulation and the reference formulation Gastro-Timelets(R) and their r espective dissolution curves were evaluated using Moore's equation: f(2) = 50 X log {[1 + 1/n Sigma(t=1)(n) Wt(Rt - Tt)(2)](-0.5) X 100} The relations hip between the ethyl cellulose content in the formulation and the dissolut ion fit factor f2 can be described as the following regression equation: Y = -0.054X(2) + 3.347X - 1.915 (r(2) = 0.99). The optimum ethyl cellulose co ntent obtained from the equation was 30.8%. The type and content of plastic izer used in the formulation to achieve the greatest f(2) were determined t o be Myvacet 9-40 at the concentration of 25%. Results indicated that using the release rare testing approach with the dissolution fit factor as a too l could provide valuable information for formulation optimization.