Final Material - Lecture 14 - Role of pH and Drug Absorption

What influences stomach pH (4) things

1) Food causes a change in pH of the stomach (increase and then decrease - bio pharm), 2) Larger volume of drinks or food, leads to bigger pH changes. 3) Drugs like antacids can influence the pH. 4) Certain disease states like Cancer can influence the pH of the stomach

As we said before, drug needs to be in the unionized form to be absorbed through the GI tract. Weak acids will be unionized in which part of the GI tract; what about weak bases

1) Weak acids will exist mostly in the unionized form in the Stomach. 2) Weak bases will exist mostly in the IONIZED form in the stomach.

The pka/pkb (have the same effect of course), will determine

1) the degree of ionization of the drug 2) This will affect the degree of its absorption. 3) The degree of solubility of the drug as well - the more ionized, the more soluble it is.

Compared to factors that influence the pH of the stomach (4), what are the factors that influence the pH in the duodenum, first portion of the small intestine. (3)

1. Stomach acid (some of it flows in when the sphincter opens) 2. Bicarbonate released from the gallbladder (double check) 3. Enzymes and their bi-products (ask why?)

Acids will have high/low pKa

Acids have higher Ka values that means lower pKa values.

Why does a plot representing Kapp against pH look exactly the same for a plot of Fu against pH

Because Kap = Fu * K0. K0 is the intrinsic parition coefficient: it is unchanged by pH or other factors. in other words, it is intrinsic to the drug or the compound and hence will be constant. Since K0 is a constant, Kap is directly proportional to Fu and will be affected by pH changes in the exact same way as Fu of the drug.

Plotting fraction of drug in the unionized form against the pH for weak acid vs weak base, what does the curve look like in both, when is pH of the solution = pKa of the drug

For weak acid, the curve will be decreasing and for weak bases, the curve will be increasing. When drug exists 50% as the unionized and 50% as the ionized form then according to the Hasselback's equation, pH will be equal to pKha.

Which part of the small intestine where drug absorption rarely occurs there?

Ileum.

When fraction unionized is 100% in the plot of kapp against pH, then on the y axis (kapp), this is the value for and when Fu is 50%, then Kapp =

K0, the intrinsic partition coefficnet, K0/2

Absorption through the stomach can markedly increase by the eradication of ...............; describe it

Mucous layer, it lines the stomach and has protective function. Any drug, regardless of its ionization state has to pass through it before it can be absorbed through the stomach. Ulcers and other diseases can eradicate the mucus layer and that can markedly increase the absorption through the stomach.

Weak bases are more ............ in the small intestine

Small intestine higher pH: less H+ and more OH- driving the equilibirum to the left. NH3 + H-O-H <-------------> OH- + NH4+

If the enzymes in the stomach or duodenum are gonna degrade the drug and render it inactive, where do we target the drug for absorption

The jejunum. (ask about that)?

Define eneteric coating

When we coat the drug-containing tablets with polymers that are pH sensitive. In other words these polymers protect the drug from an enviroenment with a certain pH and then it is meant to dissolve at a certain pH where we want the drug-containing tablet to release the drug.

Kapp is the, Ko/w

apparent partition coefficient; regular partition coefficient.

Again the intrinsic parition coefficient is pH

independent, it is not affected by changes in the pH solution where the drug will be put. Hence we use apparent partiion coefficient that takes this factor into consideration.

Graphing Kapp against Fu gives us we get a ........ relationship and the slope is

linear relationship that increases whether it is for a weak acid or weak base because they're directly proporitonal to each other, the slope is Ko or the intrinsic partiion coefficient.

Even though weak acids should theoretically be absorbed better in ............ than the ..............; most absorption occurs in ................

stomach, small intestine (because exists in the unionized form in the stomach); small intestine (because large surface area, transporters that help with drug import, etc.) - bio pharm.

Purpose of eneteric coating will be to utlimately release the drug in

the duodenum (small intestine) - we protect from degradation in the low stomach pH and release the drug safely in the duodenum.

Drawing a line from the fraction unionized at 50% to where it meets the curve (when we plot Fu against pH), gives us

the pH value when pH = pKa.

The regular partition coefficient only shows concentration of ...........; it doesn't take into account that (2 things), hence we have or we came up with ..........

the unionized form of the acid/base in the oil (hydrophobic) over aqueous phase. It doesn't take into account that pH changes and dissociation of the acids/bases in water can both affect the concentration of the unionized form of the acid/base in both phases; the apparent partition coefficient which takes these factors into account.

Drug needs to be ionized/unionized to be absorbed in gi tract

unionized.