PHARMACOLOGY
Excipient (Components of a finished drug oth-
er than the active pharmaceutical ingredient) Reasons for inclusion
Sweetners and flavourings Improve the palatability of oral medocation, to improve compliance in treatment
Bulking agents Provides bulk t the formulation to allow for easier handling during dosing or packaging
Diluent Brings the formulation to the correct volume of drug per ml of solution/suspension
Solubilizers Allows the active ingredient to dissolve in the dilluent
Stabilizer Stabilizes the active ingredient and prevents it from chemically degrading
Preservative Increase the shelf life of the formulation
Wetting agets Allows water to penetrate into a table, so that it can break up and dissolve faster in physiological
fluid
Lubricants Allows powders to flow through the machines that produce the tablets, without the formulation
getting stuck or separation of the active ingredient from the rest of the formulation
Chelators Binds certain ions and prevents bacterial growth
Antimicrobals Prevent the growth of bacteria
Table 1: Some value potential of various excipients in the formulation
General types of medicines
The principle of generic registration is considered to
1.20 2500
1.00 2000
0.80
In the regulatory system, medicines general fall into
three categories: Innovator products, Generic prod-
ucts and Compounded products. These three cate-
gories are controlled by the Medicines and Related
Substance Control Act (Act 101 of 1965):
• Innovator Products: Are the first products that are
brought onto the market. They are tested as the fi-
nal formulation to prove that the active ingredient is
properly released and that the formulation is effec-
tive. When registered, each indication is looked at
individually and requires testing usually with actual
clinical cases. The innovator company is general-
ly allowed a period of 20 years from patenting, to
sell their product with no competition. It is during
this period that they recoup their investment. At all
times, the manufacturer has to meet strict GMP re-
quirements.
• A Generic formulation: Is a formulation that con-
tains the same active ingredient as the innovator,
and is registered through an abbreviated process
known as bioequivalence or occasionally thera-
peutic equivalence. For the former process, the
pharmacokinetics of the generic and the innovator
formulation is compared. If the two formulations
can be statistically proven to be bioequivalent, it can
be registered as a generic to the innovator product.
The underlying principle comes from the pharma-
cokinetic-pharmacodynamic interactions of the ac-
tive mentioned above. If the two drugs allow for
the same plasma concentration to be consistently
achieved, there’s no reason that they won't have
the same effect. Since we do know that the man-
ufacture of the formulation can influence the plas-
ma pharmacokinetics, the formulation has to meet
strict GMP conditions, to ensure batch to batch uni-
formity. Generics are thus cheaper than the innova-
tor because they don’t have to redo the efficacy and
toxicity tests, as these have already been undertaken
by the innovator company i.e. why retest for aspects
that are already known. Since the pharmacokinetics
of the generic formulation is unknown, this is what
needs to be tested (Figure 3). With this said, the re-
quirements for comparing the pharmacokinetic
profiles of the generic to the innovator formulation
is still very strict and has to comply with numerous
requirements from the study design to the analytical
chemistry part of the study.
0.60
0.40
0.20
0.00
-20
0
-0.20
20
40
60
80
1500
1000
500
100
0
Time (h)
0 10 20 30 40 50
Time (h)
Figure 3: Illustration of how pharmacokinetics are applied in the process of proving bioequivalence of generic formulations (The graphs
in question would be supported by a full statistical evaluation for registration purposes). In this case, two different generic formulations (T)
(Each one has its own graph) are compared to the same reference product (R). In each of the