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 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: [equation: see text]. 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.
Wang
M T
MT
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC.
Tsai
F H
FH
Wang
D P
DP
D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations; D018492:Dopamine Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008787:Metoclopramide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008962:Models, Theoretical; D012597:Sclerosing Solutions / Q000737:chemistry; D012995:Solubility; D013607:Tablets
D003692:Delayed-Action Preparations; D018492:Dopamine Antagonists; D012597:Sclerosing Solutions; D013607:Tablets; C013517:ethyl cellulose; D002482:Cellulose; D008787:Metoclopramide