11.5 Formulation development
The form in which a drug is administered to patients is known as itsdosage form.
Dosage forms can be subdivided according to their physical nature into liquid,
semisolid and solid formulations. Liquid formulations include solutions, syrups,
suspensions and emulsions. Creams, ointments and gels are normally regarded
as semisolid formulations, whereas tablets, capsules, suppositories, pessaries
and transdermal patches are classified as solid formulations. However, all
these dosage forms consist of the drug and ingredients known asexcipients.
Excipients have a number of functions, such as fillers (bulk providing agents),
lubricants, binders, preservatives and antioxidants. A change in the nature of
the excipient can significantly affect the release of the drug from the dosage
form. Consequently, manufacturers must carry out bioavailability and any
other tests specified by the licencing authority if they make changes to the
dosage form before marketing the new dosage form.
The type of dosage form required will depend on the nature of the target and
the stage in the drug development. Since many promising drug candidates fail at
the preclinical and Phase I stages, a simple dosage form, such as a oral solution,
is often used for the preclinical and early Phase I clinical trials. This is in order to
keep costs to a minimum at these high risk stages of drug development. How-
ever, the manufacturer must also use the dosage form of the drug that he
proposes to use in the later clinical trials.
The types of dosage form used must satisfy criteria such as stability and
pattern of drug release. Stability studies are used to determine whether the
dosage form has an adequate potency after an appropriate period of time,
usually 2–3 years. This will determine its shelf life and recommended storage
conditions. Drug release is directly influenced by the excipients and any slow
release mechanisms employed. In both these examples suitable chemical and
biological experiments must be designed to either obtain or check the relevant
data. The results of these experiments may lead to improvements in the design of
the dosage form. They are usually carried out in parallel with the clinical trials.
11.6 Production and quality control
The manufacture of the new drug must be carried out under the conditions laid
down in the marketing authorization (MA) (see section 11.8). Since it is not
usually practical for manufacturers to dedicate a plant to the production of one
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