Page 665 - Carrahers_Polymer_Chemistry,_Eighth_Edition

628 Carraher’s Polymer Chemistry

their fluorescence counterpart because of the relative stability of the triplet state compared to the

singlet manifold. Nonradiative processes in the triplet states increase exponentially with a decrease
in triplet energies (energy gap law). Hence, phosphorescence is more difficult to observe when the

triplet states are present in very low energy levels. It is also often easier to observe phosphorescence
at lower temperatures where the thermal decay is further inhibited.
19.4 DRUG DESIGN AND ACTIVITY

There are a number of steps that should be completed before a drug is brought to market. Generally,

first a compound is found to be active in treating some illness. This may be done with cell and bac-

terial studies followed up with live animal tests. This drug is then modified in an attempt to increase

its activity and minimize negative side effects. When possible, the target is identified. The target is

typically one that is identified with the illness. The target is validated by determining the target’s
function and determining that the target activity is modified by association with the drug.

A series of studies are undertaken to evaluate the effectiveness and toxicity of the drug compound.
All along this process, large decreases in the number of compounds that make it through each hurdle
occur. Generally, extensive animal testing occurs. If the drug is believed to be effective in the treat-

ment of the illness then additional steps occur. Initially, a drug company files an Investigational New
Drug Application (INDA) with the Food and Drug Administration to get permission to begin testing
the drug in humans. The potential drug then begins a series of clinical trials with humans. Phase I
clinical trials involve testing the drug in a small number (20–100) of healthy individuals to test the
drug’s safety, tolerance, length of activity, effective dosage, and dosing schedule. Phase II clinical trials
involve testing the drug in larger numbers of individuals (100–500) that possess the particular illness

to gain additional information of efficacy, side effects, safety and appropriate dosage, and schedule.
Phase III clinical tests involve testing the drug in larger numbers of volunteers (100s–1,000s) to again
gain more information of the efficacy, side effects, and safety. In general, only one or two dosage levels

and schedules are studied in Phase III studies. If results are consistent with the drug successfully treat-
ing the illness with only minor side effects application is made to the Food and Drug Administration
to market it. Even after the drug has come to market, ongoing monitoring occurs for safety and side
effects. To accomplish such a gauntlet of testing it can cost from $200 to $800 million.
Most drugs are smaller molecules. Polymer-containing drug formulations are common. Here,
the drug is contained within some polymeric matrix that assists in controlling the release either
through control of drug diffusion through the chains or by erosion, degradation, or solubility, of the
polymer network.
But there are some drugs that are polymeric offering advantages over smaller molecules. Along
with polymers being simply depositories of the drugs, polymers can perform active roles in drug
therapy. Polymeric drugs can act in two divergent ways—as a control release agent and as a drug
itself. The polymeric drug may act in a control release manner. A polymer that contains a known
therapeutic portion can degrade releasing this portion over some time. Thus, a polymer that con-
tains the drug L-dopa (19.28) used to treat Parkinson’s disease degrades over time releasing L-dopa
over a period of time.

O R 1 O R
O

O O O OH
R
(19.28)

NH 2
Polymer-containing L-dopa

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