Bioavailability physicochemical factors affecting

Name the physicochemical factors affecting oral bioavailability. 

Despite the fact that a plethora of dietary factors could, and will, affect the absorption characteristics of phytochemicals, this area has not been systematically explored. One reason might be the complexity of dietary factors and their interactions that could affect absorption. A nonexhaustive list would include the volume and composition of the food consumed, pH, caloric density, viscosity, nutrients (carbohydrates, protein, fat, fibers), alcohol, caffeine, and the presence of other phytochemicals. Such dietary factors affect the functional status, motility, and acidity of the gastrointestinal tract in a complex manner and modify the physicochemical properties, formulation, and dissolution characteristics of the compound of interest. Calcium in dairy products, for example, has the potential to chelate tetracyclines and fluoroquinolones and, thereby, reduce their bioavailability and biological activity [31]. 

Aqueous solubility is one of the most important physicochemical properties. It is believed that a drug has to be in solution to be absorbed.35 From the pharmaceutical development point of view, the solid state form is another important factor that affects solubility, the dissolution rate, and eventually developability. The solid state form is the determinant of, to some extent, physicochemical stability, intellectual property, and formulation scalability this factor should be carefully examined and optimized. Change in crystallinerity from different chemical processes, in some cases, results in a big difference in bioavailability when the drug is delivered by a solid dosage formulation. 

When a lead compound is first discovered for a particular disease state, it often lacks the required potency and pharmacokinetic properties suitable for making it a viable clinical candidate. These may include undesirable side effects, physicochemical properties, other factors that affect oral bioavailability (see Chapter 9), and adverse metabolic or excretion properties. These undesirable properties could be the result of specific functional groups in the molecule. The medicinal chemist therefore must modify the compound to reduce or eliminate these undesirable features without losing the desired biological activity. Replacement or modification of functional groups with other groups having similar properties is known as isosteric replacement, or bioisosteric replacement. ... 

Several factors - including the route of administration, the physicochemical properties, dosage form, and the physiological state of an individual - can affect the amount of the administered dose of a drug that reaches the systemic circulation after extravascular administration. The term bioavailability (F)... 

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