Article

A level A in vitro/in vivo correlation in fasted and fed states using different methods: applied to solid immediate release oral dosage form.

Equipe de Recherche Technologique, Conception, Ingénierie et Développement de l'Aliment et du Médicament (ERT CIDAM), groupe biopharmaceutique, Faculté de pharmacie, 28 place Henri Dunant, 63000 Clermont-Ferrand, France.
European Journal of Pharmaceutical Sciences (Impact Factor: 2.99). 02/2006; 27(1):72-9. DOI: 10.1016/j.ejps.2005.08.006
Source: PubMed

ABSTRACT The first purpose of this study was to simulate the impact of food intake on drug release and absorption in vivo using a novel in vitro system which mimics the gastro-intestinal (GI) tract in man. The drug studied was acetaminophen in the form of immediate release (IR) tablets. The second purpose was to establish a level A in vitro/in vivo correlation that could predict the bioavailability of a drug instead of using difficult, time-consuming and expensive in vivo bioequivalence studies. The artificial digestive system was used to estimate the availability of acetaminophen IR tablets for absorption in fasted and fed states. The same study was performed in vivo under similar conditions. A comparison study was carried out between the classical and the novel methods to estimate the efficacy of the new in vitro system to simulate the influence of food on drug release and absorption in vivo. A level A in vitro/in vivo correlation was established with a correlation coefficient of 0.9128 and 0.9984 in the fasted and fed states, respectively. Compared to USP II method, the novel in vitro model demonstrated a high level of efficacy in mimicking the behaviour of acetaminophen IR tablets in vivo in fasted and fed states.

0 Bookmarks
 · 
64 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The characterization of biorelevant media simulating the upper part of the gastro intestinal tract in the fasted and fed states was investigated by classical determination of physicochemical parameters such as pH, osmolality, surface tension and results were compared to in vivo physiological data. Incorporation of fatty material, in order to better simulate the influence of high fat meal was also performed. Stability and characterization of this medium was studied and compared to classical FeSSIF. Micelle characterization and computer dynamic simulation were performed in order to understand the interaction between lecithin and taurocholate and possible interactions between mixed micelle and drugs. The addition of NaTc, lecithin, and/or fatty materials has no influence on pH and osmolality, whereas the presence of fatty material modifies the surface tension. Values of FaSSIF and FeSSIF are in accordance with in vivo parameters and the presence of micelles can simulate the gastrointestinal environment. Modelisation of micelles by computer simulation led to a model of mixed micelles in which structures of NaTc interact either by their hydrophilic or hydrophobic phase to give a bilayer stable model in which the lecithin molecule can insert its long carbon chain. The micelle structure is stable and can enhance dissolution of hydrophobic molecules by hydrophobic interaction with the numerous hydrophobic spaces available in the multilayer hydrophilic/hydrophobic layer.
    European Journal of Pharmaceutics and Biopharmaceutics. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Engineered metal/mineral, lipid and biochemical macromolecule nanomaterials (NMs) have potential applications in food. Methodologies for the assessment of NM digestion and bioavailability in the gastrointestinal tract are nascent and require refinement. A working group was tasked by the International Life Sciences Institute NanoRelease Food Additive project to review existing models of the gastrointestinal tract in health and disease, and the utility of these models for the assessment of the uptake of NMs intended for food. Gastrointestinal digestion and absorption could be addressed in a tiered approach using in silico computational models, in vitro non-cellular fluid systems and in vitro cell culture models, after which the necessity of ex vivo organ culture and in vivo animal studies can be considered. Examples of NM quantification in gastrointestinal tract fluids and tissues are emerging; however, few standardized analytical techniques are available. Coupling of these techniques to gastrointestinal models, along with further standardization, will further strengthen methodologies for risk assessment.
    Nanotoxicology 08/2014; · 7.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: As dissolution plays an important and vital role in the drug-delivery process of oral solid dosage forms, it is, therefore, essential to critically evaluate the parameters that can affect this process. Areas covered: The consumption of food as well as the physiological environment and properties of the gastrointestinal tract, such as its volume and composition of fluid, the fluid hydrodynamics, properties of the intestinal membrane, drug dose and solubility, pKa, diffusion coefficient, permeability and particle size, all affect drug dissolution and absorption rate. There are several dissolution approaches that have been developed to address the conditions as experienced in the in vivo environment, as the traditional dissolution being a quality control method is not biorelevant and as such do not always produce meaningful data. This review also describes the development of a systematic way that differentiates between robust and non-robust formulations by varying the effects of agitation and ionic strength through the use of the automated United States Pharmacopeia type III Bio-Dis apparatus. Expert opinion: With the improved understanding of the physiological parameters that can affect the oral bioperformance of dosage forms, strides have, therefore, been made in making dissolution testing methods more biologically based with the view of obtaining more in vitro-in vivo correlations.
    Expert Opinion on Drug Delivery 06/2014; · 4.87 Impact Factor