phospholipase, ribonuclease, and deoxyribonuclease. The drug designer must consider
these environments of varying pH combined with digestive enzymes when selecting
functional groups to be incorporated into a drug molecule. Table 1.1 presents pH values
for a variety of tissue fluids.
The pharmaceutical phase also includes the process of drug absorption from the gas-
trointestinal tract into the body fluids. In general, little absorption of a drug molecule
occurs in the stomach since the surface area is relatively small. Absorption takes place
mainly from the intestine where the surface area is greatly expanded by the presence of
many villi, the small folds in the intestinal surface. Drug absorption across the gas-
trointestinal lining (which may be regarded functionally as a lipid barrier) occurs
mainly via passive diffusion. Accordingly, the drug molecule should be largely un-ionized
at the intestinal pH to achieve optimal diffusion/absorption properties. The most signif-
icant absorption occurs with weakly basic drugs, since they are neutral at the intestinal
pH. Weakly acidic drugs, on the other hand, are more poorly absorbed since they tend
to be un-ionized in the stomach rather than in the intestine. Consequently, weakly basic
drugs have the greatest likelihood of being absorbed via passive diffusion from the gas-
trointestinal tract. Table 1.2 provides ionization constants for a variety of weakly basic
and weakly acidic drugs.
A final point of consideration (at the pharmaceutical phase) when designing drugs for
oral administration concerns product formulation. A pill is not simply a compressed
mass of drug molecules. Rather, it is a complicated mixture of fillers, binders, lubricants,
disintegrants, colouring agents, and flavoring agents. If a drug molecule is biologically
DRUG MOLECULES: STRUCTURE AND PROPERTIES 13
Table 1.1pH Values for Tissue Fluids
Fluid pH
Aqueous humor (eye) 7.2
Blood, arterial 7.4
Blood, venous 7.4
Blood, maternal umbilical 7.3
Cerebrospinal fluid 7.4
Duodenum 4.5–7.8
Intestine 6.0–8.3
Lacrimal fluid (tears) 7.4
Milk, breast 7.0
Nasal secretions 6.0
Prostatic fluid 6.5
Saliva 6.4
Semen 7.2
Stomach 1.8
Sweat 5.4
Urine 5.6–7.0
Vaginal secretions, premenopause 4.5
Vaginal secretions, postmenopause 7.0