Formulation factors
Objectives:=> To understand the formulation factors which affect the oral
absorption of drug products
The role of the drug formulation in the delivery of drug to the site of
action should not be ignored. With any drug it is possible to alter its
bioavailability considerably by formulation modification. With some drugs an
even larger variation between a good formulation and a bad formulation has been
observed. Since a drug must be in solution to be absorbed from the G-I tract,
you may expect the bioavailability of a drug to decrease in the order solution >
suspension > capsule > tablet > coated tablet. This order may not always be
followed but it is a useful guide. One example is the results for pentobarbital.
Here the order was found to be aqueous solution > aqueous suspension = capsule >
tablet of free acid form. This chapter will briefly discuss each of these
formulation types particularly in regard to the relative bioavailability.
SolutionsDrugs are commonly given in solution in cough/cold remedies and in medication
for the young and elderly. In most cases absorption from an oral solution is
rapid and complete, compared with administration in any other oral dosage form.
The rate limiting step is often the rate of gastric emptying.
When an acidic drug is given in the form of a salt, it may precipitate in the
stomach. However, this precipitate is usually finely divided and is readily
redissolved and thus causes no absorption problems. There is the possibility
with a poorly water soluble drug such as phenytoin that a well formulation
suspension, of finely divided powder, may have a better bioavailability.
Some drugs which are poorly soluble in water may be dissolved in mixed
water/alcohol or glycerol solvents. This is particularly useful for compounds
with tight crystal structure, higher melting points that are not ionic. The
crystal structure is broken by solution in the mixed solvent. An oily emulsion
or soft gelatin capsules have been used for some compounds to produce improved
bioavailability.
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