Prediction of In-vivo Blood Level with Controlled-release Dosage Forms. Effect of the Gastrointestinal Tract Time

Abstract

The process of in-vivo drug transfer is very complex in the case of oral dosage forms with controlled release. A numerical model taking all the known facts into account, including the release of the drug controlled by diffusion through the dosage form along the gastrointestinal tract, the kinetics of absorption in the blood compartment and the kinetics of elimination was constructed. Various parameters intervene in an important manner for a given drug: the size of the dosage form which is associated with the rate of release of the drug, and the dose frequency in multidosing. Some emphasis is placed upon the gastrointestinal tract time which appears to be the main and first parameter to be considered in preparing a dosage form.

Assessment of antibiotic levels in lung tissue with erosion-controlled dosage forms

“…Another approach was developed based on numerical models taking into account all the available data, e.g. the kinetics of drug release in the gastrointestine (01), the stages of absorption in the blood compartment and elimination (22)(23)(24)(25). Following this approach, another numerical model with finite differences was built, taking into account the following stages: drug release in the GI tract, absorption in the blood compartment and elimination, and transient diffusion from the blood compartment into the lung tissue.…”

Calculation of the antibiotic level in the lung tissue and bronchial secretion with an oral controlled-release dosage form

“…This problem was resolved by building a numerical model taking the following facts into account: the kinetics of drug release in the gastrointestinal tract, which is generally determined using in-vitro tests; the stage of absorption in the blood compartment and the stage of elimination. This model was successfully tested in various cases in previous papers [20], and the authors were able not only to predict the drug level in the blood obtained with controlled-release dosage forms but also to determine the effect of parameters of interest, such as the dose frequency [21] and the gastrointestinal tract time [22]. The model is described in the section on Theoretical considerations.…”

“…It is possible to calculate the concentration-time histories of ciprofloxacin after taking a controlled-release dosage form, not only in the serum [20][21][22], but also in other parts of the body such as blister fluid [24]. By using the numerical model described in this paper, the concentration-time histories of ciprofloxacin were calculated and drawn in the following places: serum (1), serum-lung tissue interface (2), mean value in the lung tissue (3), lung tissue-bronchial secretion interface (4) and bronchial secretion (5) with dosage forms in which drug release is controlled by erosion.…”

“…Another approach was t build numerical models taking all the known facts into account, namely the kinetics ( drug release from the dosage form, whatever the process of drug release, and tl~ following stages of absorption into, and elimination from, the plasma compartmel [20]. Further studies along these lines provided evidence that two factors, tt gastrointestinal (GI) tract time [21] and the dose frequency [22], should be consider~ in these numerical models. Of course, two other factors should also be accounted for they are known: the variation along the GI tract of the kinetics of drug release and the rate of absorption into the plasma [23].…”