An orally administered drug is absorbed across the GI tract, then flows through the portal vein into the liver before entering the systemic circulation. The drug is primarily metabolized in the liver and sometimes in the gut wall. So, the amount of drug reaching the systemic circulation, that is, the bioavailability of the drug, reduces substantially. Bioavailability depends on several factors, of which metabolism by the liver or gut, or the first-pass metabolism is the most prominent. Other factors include chemical stability, drug solubility and formulation. Drugs that are chemically unstable in the stomach pH or are prone to enzymatic degradation break down in the GI tract. Highly hydrophobic drugs cannot dissolve in aqueous body fluids, whereas highly hydrophilic drugs cannot cross the lipid bilayer of cells and are poorly absorbed. Drug formulation influences bioavailability by affecting drug dissolution. Minimizing drug particle size, using a drug's salt, crystal, or hydrate form or adding enteric coatings can help drugs get easily dissolved and increase their bioavailability.