The present investigation deals with the result of a mathematical and an analog computor analysis of the kinetic relationships governing the rate of release of (drugs from sustained-release dosage forms. Two types of release have been considered, those described by zero-order and those that can be described by first-order kinetics. In addition, mathematical equations are derived that permit the calculation of doses and of release constants that will give a blood concentration versxs time curve most closely approximating an "idealized" curve.
HE XPPKOACII most often used in the kinetic Ttreatment of biologic data is that involving formulation of a mathematical model, the comparison of this model with in vivo findings, and finally the adjustment of the model and its constants to accommodate the in niwo results. Once a suitable model has been establishcd, the complete interdependency of the model's parameters can be examined,l subject to the suitability of the model chosen. These parameters may be divided into two types, those under the control of the formulator, i.e., the dosage form, release pattern, and rate, etc., and those that arc imposed upon the model by the system studied, i.e., the absorption, distribution, and excretion (ADE) pattern for the drug in thc body. In the past, the major emphasis has been placed on the ADE parameters with relatively little attention being given to the dosage form release rate and pattern, not only because these studies are more difficult to carry out, but also because initially it was of particular concern to study the suitability of various models as simulations of the body's ADE eapabili ties. It seemed reasonable a t that time to assume that in cases where the drug has been administered by injection or orally in some readily available form, e.g., drug in solution, the effect of the dosage form release pattern might safely be neglected ; for nonreadily available forms, particularly sustained-release dosage forms, this assumption cannot be made as the dosage form release pattern and its rate un--~~