IN-VIVO EVALUATION OF CONTROLLED-RELEASE PRODUCTS

A theoretical investigation has been conducted to understand the decon volution method used for evaluating the in vivo release rate of an ora l controlled-release product from the plasma drug concentration versus time profile. The theory is based on well-accepted pharmacokinetic co mpartmental models. The cumulative amount of drug released from a dosa ge form can be partitioned into two parts: the amount already absorbed and the amount released but still remaining at the absorption site in the gastrointestinal tract. The cumulative amount absorbed at any tim e, t, can be estimated from the plasma concentration versus time profi le by the compartmental model-based Wagner-Nelson method or Loo-Riegel man method. We have derived a mathematical expression relating the amo unt at the absorption site with the plasma drug concentration versus t ime profile assuming a first-order absorption rate process. The differ ence between the in vivo release profile and the in vivo absorption pr ofile is illustrated. Because what determined in vitro is the release profile, it should preferentially be correlated with the in vivo relea se profile, not the absorption profile. However, when absorption is mu ch faster than elimination, the estimated absorption profile is a good approximation of the release profile. In this circumstance, it is adv antageous to use absorption profiles to demonstrate correlation of in vitro and in vivo dosage form performance to avoid the noise inherent in the numerical method of deriving the exact in vivo release profile.