Extent of ionization
- Henderson Hasselback equation
Ch10: Biopharmaceutical Data of the GI Tract
- explains the anatomy and function of GI tract in
relation to drug absorption.
▸ Absorption
◽ is the process of transferring chemical substances
from the GI tract through its wall into the blood &
lymphatic stream.
◾ Drug absorption is the movement of the drug from its
site of administration into the bloodstream.
◾ Most of the absorption of food takes place in the small
intestine
◾ Most drugs are absorbed by passive diffusion in form
of the nonionized moiety. This has a higher lipid
solubility according to the pH partition hypothesis
FACTORS AFFECTING DRUG ABSORPTION
▸ PHYSIOLOGICAL
1. membrane physiology
2. surface area of the absorbing organ
3. gastric emptying
4. motility
▸ PHYSICO-CHEMICAL
1. lipid-water partition coefficient
2. pKa of the drug & the pH of the body fluid
3. salts
4. crystal vs amorphous
5. formulation factors: dosage form
Ch7: pKa and Degree of Ionization
Categories of drugs according to their physical behavior in
aqueous solutions:
1. Strong electrolytes
2. Non-electrolytes
3. Weak electrolytes (depend on the pKa of the agent
and the pH of the medium
-most of the drugs are either weak acids or weak
bases
General pattern:
◽ acidic drugs are better absorbed in stomach (since in
non ionized form)
◽ basic drugs are better absorbed in small intestine
(non ionized form)
pH in GIT
◾ Stomach (acidic)
- basic drugs are ionized
- acidic drugs are non-ionized
- acidic drugs expected to be better absorbed
◾ Small intestine
- basic drugs are NON-ionized
- acidic drugs are ionized
- basic drugs are expected to be better absorbed
Lipid-Water Partition Coefficient
- denotes the ratio of the concentration of a drug in
two immiscible or slightly miscible phases
◽ For a drug to be absorbed, it has to cross cytoplasmic
membranes and eventually get out of this membrane to
reach the bloodstream.
◽ For a drug to cross this membrane barrier, it has to be
soluble in the lipid component of this barrier. It should
also have to be soluble in the aqueous phase to be able
to partition out of the membrane.
drug → cytoplasmic membrane → bloodstream
◽ ratio of solubility in oil : solubility in water
◽ high partition coefficient → more lipid soluble
Importance:
▸ useful in vitro guide to the absorption potential of a drug
▸ indicator for storage of drugs in fat
▸ reliable for absorption from the stomach, the buccal
cavity, the colon and the skin.
Ch9: Physicochemical Factors
Particle Size
Dissolution
- the rate at which the drug/ formulation dissolves
◽ dissolution rate given by the Noyes- Whitney equation
◽ smaller particle size → higher dissolution
◽ Drug product must have uniform particle size to have a
predictable absorption
Salts/Salt formation
◽ different salts have different solubilities
◽ generalyl, salt forms are more water soluble than free
drugs
◽ higher water solubility → faster dissolution → better
absorption
Polymorphism Important points to remember GET/GER:
- is the phenomenon that a drug may exist in different 1. Some drugs can affect GET/ GER
crystalline forms, polymorphs. It exist only in the solid
- anticholinergics increases GET / slow GER
state.
- metoclopramide decreases GET / faster GER
1. Amorphous form
2. Disease states / age of the patient can also affect
- less stable → increased solubility/higher dissolution gastric emptying
rate 3. Normal GET
2. Crystalline form - approximate 2 hrs. (advise drugs to be taken 2 hrs
- more stable → decreased solubility due to rigid before or 4 hrs. after meals for drugs affected by food)
structure
Example of a drug that exist as polymorphs:
Motility/ Interaction with GI contents
INSULIN ◽ Food can increase or decrease absorption
◾ crystalline form –used for long acting (Glargine) ◽ In general: slower absorption of drugs taken with meals
◾ amorphous form – used for short acting (Lispro, Aspart) ◽ Metal cations can chelate with drugs, decreasing
absorption (ex. tetracycline, fluoroquinolones)
◾ mixture of crystalline + amorphous (70:30) – used for
intermediate acting ◽ Fatty meals increase griseofulvin absorption

Complex formation
Drugs whose absorption is reduced, delayed, increased, or
Chelates not affected by the presence of food.
- complexes that involve ring like structure formed by
interaction
Ex: tetracycline + Ca → decreased solubility → less REDUCED DELAYED
absorption
▸ Amoxicillin ▸ Acetaminophen
◽ Solubility is an inherent characteristic of the drug. Drugs
▸ Ampicillin ▸ Cefaclor
must be water soluble to dissolve in aqueous media of
▸ Aspirin ▸ Cephalexin
stomach.
▸ Isoniazid ▸ Digoxin
◽ A pre-requisite for absorption is that the drug must be
present in aqueous solution at the absorption site. ▸ Levodopa ▸ Potassium ion
▸ Furosemide ▸ Sulfadiazine
Manufacturing factors/ Formulation factors ▸ Penicillin G ▸ Sulfadimethoxine
Compatibility of excipients and drugs ▸ Tetracycline ▸ Sulfanilamide
▸ Rifampin ▸ Sulfasymazine
a. Disintegrant
▸ Doxycycline ▸ Sulfisoxazole
- too little disintegrant → tablet will not disintegrate
b. Lubricants
- Hydrophobic → too much will decrease dissolution

INCREASED NOT AFFECTED

PHYSIOLOGIC FACTORS AFFECTING DRUG
ABSORPTION ▸ Hydralazine ▸ Chlorpropamide
◾ Gastric emptying time (GET) / Gastric emptying rate ▸ Hydrochlorothiazide ▸ Glibenclamide
(GER) ▸ Metoprolol ▸ Glipizide
▸ Oxazepam ▸ Metronidazole
◾ Motility (Interaction with GI contents)
▸ Phenytoin ▸ Prednisone
GET/ GER ▸ Propoxyphene
- inversely related ▸ Propanolol
- Short GET → less time for drug to stay in the stomach ▸ Theophylline
to move to small intestine for absorption
- High GER → faster travel time to small intestine for
absorption Questions:
◽ Short GET → high GER → better absorption What is the absorption of a non ionized drug?
A non ionized drug which is lipid soluble has a better
absorption

Having a high partition coefficient, what happens to

absorption?
More lipid soluble thus better absorption