Most drugs have polar and non-polar characteristics or are weak acids or bases.
For drugs which are weak acids or bases the pKa of the drug and the pH of the GI tract fluid and the pH of the blood stream will control the solubility of the drug and thereby the rate of absorption through the membranes, lining the GI tract. Brodie et al. Brodie reasoned that when a drug is ionized it will not be able to get through the lipid membrane, but only when it is non ionized and therefore has a higher lipid solubility. Brodie tested this theory by perfusing the stomach or intestine of rats, in situ, and injected the drug intravenously. He varied the concentration of drug in the GI tract until there was no net transfer of drug across the lining of the GI tract.