An efficient method for computer-aided dosage form design.
It is desirable to have slow-release dosage form to be taken once daily, or at most twice daily, as compared to three or four times in a single day. However, the existing computer-aided dosage form design method requires a large amount of computer time when applied to nonlinear disposition drugs. This large commitment of computer time makes it inconvenient to study the feasibility for prolonged-release products containing such drugs. Instead of evaluating all possible combinations of the amount of dose and release rates that produce acceptable steady-state plasma concentrations, only the contour of the dose-release rate domain needs to be determined. An image boundary tracking method has been used to determine such contours. When combined with several modifications of the numerical solution process, the acceptable dose and release rate constants can be determined efficiently. When this modified boundary tracking method was applied to phenytoin, which exhibits nonlinear disposition, the required computer time was reduced to about 5% of the previous method, making the dosage form feasibility assessment practical.
Lam
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CF
Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston 29425-2503.
Jiang
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Q
Notari
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RE
D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004360:Drug Therapy, Computer-Assisted; D008954:Models, Biological; D017711:Nonlinear Dynamics
D003692:Delayed-Action Preparations