ABSTRACT:
A major objective in the pharmaceutical industry is to develop new drugs with Good Oral Bioavailability that is a highly desirable property for molecules under investigation in the drug- discovery process because it opens up a variety of formulation possibilities, dosing conditions and leads to better patient compliance. Good oral bioavailability occurs when the drug has Maximum Solubility and Maximum Permeability at the site of absorption. Hence the extent of absorption of the drug in-vivo could be predicted based on permeability and solubility measurements in-vitro. Thus the Assessment of Intestinal Permeability represents one essential part in the prediction of oral any new drug candidate. Moreover, permeability information provides the formulation scientist with both Biopharmaceutical as well as Regulatory Insight during a prototype formulation. So far as a number of in-vitro methods for assessing the intestinal permeability of a given drug candidate have been developed and recently reviewed. In the last decade, the use of Caco-2 cell monolayer has gained in popularity as an in-vitro primary absorption screening tool in several pharmaceutical companies and several examples of successful correlation with human absorption have been reported. Spontaneously differentiate to express morphological (polarized columnar cells) and functional characteristics of mature small-intestinal enterocytes. Four times higher in transepithelial resistance compared to HT29-H monolayer. It expresses various drug metabolizing enzymes like, aminopeptidase, esterase, and sulfatase. It express various transporters like, uptake transporters responsible for the absorption of bile acids, large neutral amino acid, biotin, monocarboxylic acids and PEPT1, and efflux transporters like, P-glycoprotein, BCRP, MRP2 and MRP3. Expression of brush border enzymes such as lactase sucrase, isomaltasedipeptidylpeptidase IV.