Gastrointestinal Transit Absorption

Furthermore, the Pefr data can be integrated with solubility/dissolution data to predict the oral absorption from the solid dosage form (see Chapter 10). Gastrointestinal transit absorption model (GITA) [12, 13], advanced compartmental absorption and transit model (ACAT, GastroPlus), advanced drug absorption and metabolism model (ADAM, SimCYP) and so on have been reported as useful integration models (see Chapter 10). 

Tolli, J., Absorption, gastrointestinal transit, and tablet erosion of felodipine extended release (ER) tablets, Pharm. Res. 1993, 10, 709-714. 

Marvola, M., Aito, H., Pohto, P., Kannikoski, A., Nykanen, S., Kokkonen, P., Gastrointestinal transit and concomitant absorption of verapamil from a single-unit sustained-release tablet, Drug Dev. Ind. Pharm. 1987, 13, 1593-1609. 

Riley SA, Sutcliffe F, Kim M, Kapas M, Rowland M, Turnberg LA. The influence of gastrointestinal transit on drug absorption in healthy volunteers. Br J Clin Pharm 1992 34 32-39. 

The expected Cmax and AUC for each of the profiles are listed in Table 3. The profiles are predicted to show an acceptable range of Cmax values with around 20% difference between the fast and medium formulations and between the medium and slow formulations. The predicted differences in AUC are only related to the slightly different content of the three formulations, reflected in the Finf values (100% for the fast formulation and 102% for the other formulations). Normally, AUC is not expected to be rate-dependent unless there is some non-linear process involved in the disposition of the drug or drug release or absorption is very slow compared to gastrointestinal transit time. Given the predicted Cmax differences, these three formulations are appropriate choices for an IVIVC study as they show acceptable in vitro and predicted in vivo differences. 

Kimura T, Higaki K (2002) Gastrointestinal transit and drug absorption. Biol. Pharm. Bull. 25 149-164. 

The effect of food on gastrointestinal transit and drug absorption of a 125... 

THE EFFECT OF FOOD ON GASTROINTESTINAL TRANSIT AND DRUG ABSORPTION... 

Schultze JDR, Waddington WA, Ell PJ, Parsons GE, Coffin ME, Basit AW. Concentration-dependent effects of polyethylene glycol 400 on gastrointestinal transit and drug absorption. Pharm Res 2003 20(12) 1984-1988. 

There are a number of physicochemical properties of an API that are impacted upon size reduction, which need to be considered while resolving pharmaceutical problems related to solubility limitations. Clearly, dissolution rate and its dependence upon particle size reduction is one of those critical properties (Ross and Morrison, 1988 Rabinow, 2004 Kocbek et al., 2006). For example, in the case of oral administration of a poorly water-soluble API, the increase in dissolution rate attendant with size reduction provides for more drug in solution, and available for absorption, during its gastrointestinal transit (Chaumeil, 1998 Merisko-Liversidge et al., 2003 Patravale et al., 2004 Pouton, 2006). 

Most peptides and proteins are currently formulated as parenteral formulations because of their poor oral bioavailability. Nevertheless, oral delivery of peptides and proteins would be the preferred route of administration if bioavailability issues could be overcome, as it offers the advantages of convenient, pain-free administration. Although various factors such as permeability, chemical and metabolic stability and gastrointestinal transit time can affect the rate and extent of absorption of orally administered peptides and proteins, molecular size is generally considered the ultimate obstacle [36]. 

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