The chemical form significantly affects dissolution. Chemical modifications can involve changing the chemical structure of a drug to a form, which is significantly different from the active drug entity. This form can, however, provide a similar therapeutic response since within the body it breaks down into the active entity. Ideally, a drug molecule should have sufficient aqueous solubility for dissolution; an optimum oil/water partition coefficient to provide diffusion through several bilipid layers; and stable chemical groups which will interact with the receptor site. Such an ideal molecule does not usually exist in nature, and so chemical modifications are generally directed toward that part of the molecule, which is responsible for the hindrance in the overall absorption process. For example, it is desirable to restrict the absorption of a sulfonamide if it is to provide a local action in the gastrointestinal tract. This can be achieved by the synthesis of chemical forms such as succinylsulfathiazole, phthalylsul-fathiazole, phthalylsulfacetamide, and salazosulfapyridine, with a free carbonic acid structure which can ionize in the gut. These chemical modificaions, which lead to an ionized species, decrease the lipid-water partition coefficient sufficiently to restrict the absorption of the sulfonamides. The antibacterial activity is unfolded when the amide links are broken down by hydrolysis, thus releasing the free and active sulfonamide structures. The aqueous solubility of drugs can be increased by modifications, such as sulfacarboxychysoidine, and so on, a sulfonamide designed on the basis of insight gained with prontosil and pontosil rubrum. The introduction of dicarbonic acid and sugars into the chemical structure increases the aqueous solubility of tuberculostatic, thiosemicarbazone, and isonicotinic acid hydrazide, erythromycin, and chloramphenicol also provide increased aqueous solubility, Table 1 lists several examples of drugs whose water has solubility been increased as a result of chemical modifications. On the other hand, a decrease in the ionization will result in better absorption, as demonstrated for ganglionic blocking agents of the onium type such as hexamethonium. By switching to tertiary amines, such as mecamylamine and pempidine, one obtains drugs that are more steadily and completely absorbed.
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